Management and outcome of multifetal gestation in a 35-year-old woman with childhood-onset membranoproliferative glomerulonephritis type I.

A 35-year-old woman with membranoproliferative glomerulonephritis type I had quintuplet gestation after induced ovulation. Her serum creatinine level and estimated glomerular filtration rate were 0.86 mg/dL and 61.5 mL/min/1.73 m2 before pregnancy. Blood pressure was normal and urinary protein to creatinine ratio was 0.2 g/gCr. Prednisolone 10 mg on alternate-day administration was continued during pregnancy. At 10 weeks of gestation transvaginal selective embryo reduction was performed and five embryos were reduced to twins. Hypertension occurred at 20 weeks of gestation. She developed nephrotic syndrome and serum creatinine level increased to 1.29 mg/dL. Elective cesarean section was performed at 28 weeks of gestation and dichorionic diamniotic twins were born. After delivery blood pressure, serum creatinine level, estimated glomerular filtration rate and serum albumin level in their mother returned to baseline. Her twin infants were well at discharge from neonatal-intensive-care-unit. Incidence of multifetal pregnancies due to the improvement of assisted reproduction technologies and ovulation-inducing hormones has been increasing. Management for multifetal pregnancy in women with chronic kidney disease will be needed further.

Pregnancy in 4 women with childhood-onset steroid-sensitive nephrotic syndrome.

Four women with childhood-onset steroid-sensitive nephrotic syndrome (SSNS) had 5 pregnancies. Their age at onset of SSNS was between 4 and 10 years, and age at pregnancy was between 21 and 31 years. Three patients with frequent relapsing nephrotic syndrome (NS) continued to relapse after 20 years of age. Two of them had relapses during 6-32 gestational weeks of pregnancy and were treated with prednisolone (PSL) 10-45 mg/day. One patient delivered a normal baby on 2 pregnancies. Another developed superimposed preeclampsia and her infant showed asymmetrical type of intrauterine growth restriction (IUGR). There was no relapse during pregnancy in 2 patients, including 1 with frequent relapses, who had no relapse over 5 years preceding the pregnancy. In all four patients, normal renal function and complete remission were noted at the last follow-up. Their 5 infants were well at 1-7 years of age. Although hypertension, growth failure of the placenta, and IUGR of the baby may complicate the pregnancy, most pregnancies with SSNS seem to result in normal birth, even when relapses occur during pregnancy and are treated with PSL.

Long-term prognosis of 4 children with steroid-sensitive nephrotic syndrome and relapse after 30 years of age.

Some children with steroid-sensitive nephrotic syndrome (SSNS) have been reported to suffer relapses in adulthood, but the clinical course of such adults is unclear. Four children with SSNS suffered relapses after 30 years of age. Those 4 patients developed frequently relapsing nephrotic syndrome (NS) between 2 and 10 years of age. They were treated with prednisolone (PSL) combined with cyclophosphamide in 3 patients, mizoribine in 2, and cyclosporine in 1 during childhood, and with cyclosporine in 2 during adulthood. After 20 years of age, the frequency of relapses gradually decreased. The last relapse occurred between 33 and 39 years of age, and proteinuria disappeared within 1 month after the start of treatment with PSL. At the last follow-up, all 4 patients continued to receive PSL, had normal renal function, and were in complete remission of NS when they were between 33 and 41 years of age. Although the long-term outcome of SSNS is usually considered to be favorable, pediatricians should be aware that some children with SSNS may require long-term treatment during adulthood.

A girl with Peters plus syndrome associated with myelomeningocele and chronic renal failure.

A girl was born with sclerocornea of the right eye, corneal staphyloma of the left eye and lumbar myelomeningocele. The myelomeningocele was repaired soon after birth. The corneal staphyloma was perforated during infancy. She received keratoplasty and achieved light perception. Her right kidney revealed multicystic dysplasia and was non-functioning at birth. She had neurogenic bladder, and her renal function deteriorated gradually. Peters plus syndrome was diagnosed based on anterior ocular segment anomalies, short stature, developmental delay and characteristic face. Anterior ocular segment anomalies are rare findings, but seem to be occasionally associated with spina bifida and renal anomalies. Myelomeningocele and chronic renal failure in patients with Peters plus syndrome have not been reported to our knowledge.

A male patient with malignant lymphoma and thyroid papillary carcinoma after pediatric renal transplantation.

A 6-year-old boy received renal transplantation and was treated with methylprednisolone, cyclosporine A and mizoribine. He developed Epstein-Barr virus-associated malignant lymphoma at 10 years and thyroid papillary carcinoma at 20 years of age. Chemotherapy for the malignant lymphoma was done after withdrawal of cyclosporine A and mizoribine, and thyroidectomy was performed for thyroid carcinoma. He was well and his serum creatinine was 1.0 mg/dl at 22 years of age. To our knowledge, no pediatric renal transplant recipient who had thyroid carcinoma or two different types of tumor has been reported in Japan.

A boy with membranous nephropathy after allogeneic bone marrow transplantation.

A 6-year-old boy developed bronchiolitis obliterans organizing pneumonia and nephrotic syndrome 5 months after allogeneic bone marrow transplantation from an unrelated donor for acute lymphoblastic leukemia. His renal biopsy showed membranous nephropathy. He was treated with prednisolone and cyclosporine A. Proteinuria disappeared 3 months after the onset of nephrotic syndrome. To our knowledge, this patient is the youngest case with nephrotic syndrome due to membranous nephropathy after hematopoietic stem cell transplantation.

Head circumference and development in young children after renal transplantation.

BACKGROUND: Growth impairment, microcephaly and developmental delay in young children with chronic renal failure improve after successful renal transplantation. There have been few reports on head circumference (HC) and development after transplantation. METHOD: Standard deviation scores (SDS) of height and HC and developmental quotient (DQ) after successful renal transplantation were evaluated in 12 recipients under 5 years of age. At the time of transplantation their mean age was 2.5 years and mean bodyweight was 9.0 kg. RESULTS: Mean height SDS was -3.0 at transplantation and increased to -2.3 at 1 year after transplant (P = 0.002). Mean HC-SDS increased from -1.4 to -0.9 at 1 year after transplant (P = 0.02). As for each category of DQ examined 1 year after transplant, mean scores of gross motor function, basic practice, personal relations, speech and recognition increased from 69 to 90 (P = 0.007), from 77 to 102 (P = 0.02), from 87 to 103 (P = 0.04), from 71 to 90 (P = 0.0006), and from 88 to 101 (P = 0.03), respectively. CONCLUSION: In young children, physical growth, HC growth and DQ scores increased 1 year after transplantation. Dialysis and transplantation program should be planned in young children with end-stage renal failure in anticipation of growth and development of each patient.

Membranoproliferative glomerulonephritis in a girl and her mother.

A girl and her mother were diagnosed as having membranoproliferative glomerulonephritis (MPGN) type I. Microscopic hematuria and proteinuria presented at 9 years of age in the mother and at 14 years in the daughter. Both had persistent hypocomplementemia and were treated with steroids. When the mother was 40 years old, proteinuria was still continuing and creatinine clearance was 64.4 ml/min per 1.73 m(2). When the daughter was 15 years old, microscopic hematuria was still continuing. To our knowledge, familial cases of MPGN in two generations have not been reported in Japan.

Steroid-sensitive nephrotic syndrome in two families.

Few reports of familial cases of steroid-sensitive nephrotic syndrome (SSNS) are available. Of 123 children with SSNS, four cases in two families are presented. Two sisters and a father and his daughter developed SSNS. The incidence of SSNS siblings in Japan seems to be similar to the incidence reported in other countries. SSNS in two generations is rare. To our knowledge, cases of SSNS in a parent and a child in Japan have not been reported.

IgA nephropathy associated with leukemia and lymphoma: report of two cases.

IgA nephropathy (IgAN) associated with leukemia and lymphoma has not, to our knowledge, been reported in children. Two children suffering from these diseases are described here. One patient developed IgAN at the end of 5 years' chemotherapy for acute lymphocytic leukemia. The other had microscopic hematuria 3 years before the onset of non-Hodgkin lymphoma, and hematuria continued during chemotherapy. Each disease occurred after a long interval, and the clinical courses did not run parallel. The association was thought to be incidental in our cases. Chemotherapy with adrenocorticosteroids and immunosuppressants [6-mercaptopurine (6-MP) and cyclophosphamide (CY)] for leukemia and lymphoma did not affect the clinical course of IgAN.

Transition of children with membranoproliferative glomerulonephritis to adolescence and adulthood.

BACKGROUND: Many chronic renal diseases in children, including membranoproliferative glomerulonephritis (MPGN), often continue into adulthood, and these patients require continuing management. Despite the importance of the topic, there has been limited discussion about the problems of transition in children with continuing renal disease. We report our experience in patients with MPGN, as they matured from childhood to adolescence and adulthood, so-called "carry-over" cases. METHODS: The clinical course of diffuse MPGN in 27 children was retrospectively reviewed. Patients were over 18 years old at the end of follow-up. RESULTS: The mean follow-up period was 12.6 years; 20 children (74%) were identified by school urinary screening. The clinical course was favorable, and none of the patients progressed to end-stage renal failure during follow-up. However, eight patients (30%) continued to demonstrate proteinuria; two patients were nephrotic. Four patients were non-compliant and discontinued medication by themselves. Three patients were still on low dose of alternate-day (ALD) prednisolone. Twenty patients finished the treatment and were followed for an average of 4.6 years. Only one demonstrated trace amounts of proteinuria 1 year after discontinuing ALD prednisolone. CONCLUSIONS: MPGN often continues during maturation from childhood to adulthood, and patients are usually referred to adult nephrologists. Good communication between pediatric and adult nephrologists is important. In addition, more in depth explanation and reeducation about their disease and its management are helpful when these patients reach adolescence. These measures will improve their care and help to assure compliance with their medication regimen.

Adult height of three renal transplant patients after growth hormone therapy.

Three girls with normal growth hormone secretion had received renal transplantation when aged 2 to 6 years. They had had severely retarded growth (SD for height score was -7.4 to -3.7) at the time of transplantation. After renal transplantation, steroid was withdrawn and they were treated with recombinant human growth hormone; they subsequently reached adult heights of 145 to 156 cm. The SD for adult height score was -2.6 to -0.3. The adult height in two patients was over their target height, calculated using the mean of the parents' height. This report shows the efficacy of steroid withdrawal and recombinant human growth hormone therapy in achieving adult height in these three girls after renal transplantation.

Final height in children with steroid-sensitive nephrotic syndrome.

BACKGROUND: Growth retardation following steroid treatment in children is a major problem. Reduction of steroid dose has been tried using immunosuppressive agents such as cyclosporine A or mizoribine in children with frequently relapsing nephrotic syndrome. Few reports concerning final height in steroid-sensitive nephrotic syndrome (SSNS) are available. METHOD: Patients who developed SSNS before 15 years of age and reached their final height were retrospectively studied by standard deviation score (SDS) of height and target height calculated by their parental height. RESULTS: A total of 34 patients were evaluated for their final height. The mean age at onset of SSNS was 8.0 years and the mean age at last follow up was 21.6 years. In total, 22 patients had frequent relapses and were treated with cyclophosphamide, mizoribine or cyclosporin A. All patients had normal renal function at the last evaluation. The mean final height was 168 cm in males and 155 cm in females. The mean height SDS was 0.37 at the time of onset and was -0.43 when they reached their final height (P = 0.0001). The final height was a mean of 2.5 cm below target height and was significantly lower than their siblings (P = 0.007). Final height of two boys who continued to have frequent relapses during puberty and were not treated with cyclosporin A was 146 and 150 cm. CONCLUSION: Final height in children with SSNS was slightly affected by steroid treatment and two patients had severe growth retardation.

Clinical course of congenital nephrotic syndrome and Denys-Drash syndrome in Japan.

BACKGROUND: The prognosis of Japanese patients with congenital nephrotic syndrome (CNS) and Denys-Drash syndrome (DDS) is not clear. METHODS: Five patients with CNS and four patients with DDS, which causes secondary CNS, were studied retrospectively. RESULTS: Seven patients were sporadic and two DDS patients were identical twins. Five CNS patients presented with edema within 3 months of birth. In four DDS patients, edema was not noted and end-stage renal disease developed between 7 months and 6 years of age. Of these five CNS patients, one patient had cerebral thrombosis and cytomegalovirus pneumonia at the onset and another patient died during dialysis. Frequent intravenous albumin administration required, growth and development during infancy were varied. Of the nine patients with CNS and DDS, seven received renal transplantation and were alive with functioning grafts at the last follow up. Catch-up growth was observed in five patients after transplantation. Five school-aged patients attended school and received adequate grades and two adults worked full-time. Of the DDS patients, dysuria due to hypospadias persisted in one patient and treatment for hypogonadism was needed in one patient. CONCLUSIONS: CNS and DDS were diagnosed early after onset and adequate treatment was started. Growth and development after renal transplantation were relatively good. Thrombotic episodes or severe infection in CNS patients was difficult to manage and complications resulting from DDS affected the quality of life.

Familial cases of Henoch-Schönlein purpura in eight families.

BACKGROUND: Familial cases of Henoch-Schönlein purpura (HSP) have rarely been reported. METHODS: Familial cases of HSP were reviewed by medical records of 418 children with HSP. RESULTS: Two members developed HSP in eight families. HSP occurred in a mother and her daughter in one family and in siblings, including one pair of twin sisters, in seven other families. Four pairs of patients developed HSP at the same age. Three pairs presented HSP within 1 month of each other and the other pairs presented HSP between 9 months and 5 years. Seven patients had a history of allergic diseases. The clinical courses of 12 patients were reviewed. Upper respiratory tract infection preceded HSP in 10 patients, two of whom had elevated antistreptolysin-O titers. No pairs of patients in a family received the same drugs before the onset of HSP. Abdominal pain was noted in eight patients, arthralgia in six and nephritis in four. Severity of skin lesions, presence of abdominal pain and nephritis, and serum IgA levels at the acute stage varied among family members of HSP. CONCLUSIONS: The incidence of HSP in family members of children with HSP seems to be high. Onset at the same age and onset of HSP within 1 month in siblings have not previously been reported. There were no characteristic or similar findings between two patients of the same family. No trigger or genetic factor causing HSP was identified.

Hypocomplementemia and membranoproliferative glomeruloneophritis in children.

BACKGROUND: The incidence of hypocomplementemia detected in the school urinary screening program in Kanagawa Prefecture, Japan, and the number of new patients with membranoproliferative glomerulonephritis (MPGN) diagnosed in our institution were decreasing during the period between 1974 and 1997. Follow-up of this study was performed during the period between 1998 and 2003. METHODS: A total of 1,230,398 urine specimens in elementary and junior high school were examined between 1980 and 2003. Serum C3 was measured in children with abnormal urinary findings. Fifty-nine children were diagnosed as having idiopathic MPGN in our hospital between 1974 and 2003. RESULTS: Serum C3 was measured in 1546 school children with abnormal urinary findings, and 34 had hypocomplementemia between 1980 and 2003. Among 264 children in whom C3 was measured between 1998 and 2003, only 4 had mild hypocomplementemia of 83-86 mg/dl (normal, 87-157 mg/dl). Between 1974 and 2003, 59 children (8.8%) were diagnosed as having idiopathic MPGN in our hospital, whereas only 2 were diagnosed during the period between 1998 and 2003. CONCLUSIONS: The incidence of hypocomplementemia detected in school urinary screening and new cases of MPGN continue to decrease in our experience.

Henoch-Schonlein purpura with hypocomplementemia in children.

BACKGROUND: The clinical course and prognosis of Henoch-Schonlein purpura (HSP) associated with hypocomplementemia are not clear. METHODS: The clinical findings of 10 children with HSP and hypocomplementemia were studied. RESULTS: Purpuric rash in all patients, abdominal pain in five, and arthralgia in nine were noted. The findings in HSP were not different from others with HSP. In eight patients, infection preceded hypocomplementemia. Serum levels of CH50, C3 or C4 were depressed variously. Complement levels returned to normal within 5 weeks in all patients. Antistreptolysin-O (ASO) titer was elevated in all patients and nephritis occurred in eight patients. Six patients had generalized edema and hypertension. Macroscopic hematuria occurred in two patients and heavy proteinuria in five patients. One patient was diagnosed as having poststreptococcal acute glomerulonephritis (PSAGN) combined with HSP nephritis according to renal biopsy findings. In three of eight patients with nephritis, abnormal urinary findings continued for more than 1 year. CONCLUSIONS: Hypocomplementemia in children with HSP was transient and was not related to severity of HSP. Incidences of elevated ASO titer and nephritis were high. The nephritis resembled PSAGN during the acute stage and long-term clinical courses varied. These findings suggest PSAGN may be associated with HSP nephritis.