Renal transplantation (RT) is the optimal form of renal replacement therapy for children with end-stage renal disease (ESRD). Although in the previous textbooks and reviews there were several contra-indications to RT, most of which have been resolved to date. We discuss the contra-indications to pediatric RT and delineate the indications of RT through the recent literatures and our experiences.
Absolute contra-indications to RT include only uncurable malignacy and chronic HIV infection because the risk of immunosuppressive therapy definitely outweighs the benefits of RT in these cases.
Relative contra-indications include chronic infection of hepatitis B and hepatitis C virus, ABO blood type incompatibility, positive T cell crossmatch, mental retardation, the primary disease of focal segmental glomerulosclerosis and primary oxalosis, severe lower urinary dysfunction, severe cardiac dysfunction, and small children. However, recent advance in the pre-, intra- and post-operative treatment enables us to expand RT previously regarded as contraindication.
RT for patients with the primary disease of focal segmental glomerulosclerosis and primary oxalosis was a matter awaiting solution. In primary oxalosis, combined liver and renal transplantation may be a better solution to date. In recurrent focal segmental glomerulosclerosis, early use of plasmaphresis leads to prolonged allograft survival and prophylactic plasmaphresis reduces the incidence of recurrence. Successful RT across ABO barrier is possible with adequate pre- and post-transplant management and may be established as a standard procedure in Japan to settle a shortage of cadaveric allografts. The cardiac performance of an uremic patient is one of the most important determinant influencing the decision of putting on the waiting list. Nevertheless, RT itself eliminates several factors of cardiotoxicity and subsequently improves cardiac function. The recipients with hepatitis B and C infection have an increased risk of hepatic cirrhosis and hepatocellular carcinoma and interferon therapy after RT is contraindicated because of the high risk of triggering acute rejection. Therefore, sufficient treatment for hepatitis is required before RT.
According to a report from the NAPRTCS registry, the age under 2 years of the recipients was a significant risk factor for decreased graft survival because of kinking of redundant donor vessels and subsequent vascular thrombosis. Therefore, most of centers wait until children with ESRD grow enough to be recipients. Recently, a few leading centers attempted to perform RT from living donors for small pediatric children. RT may be successfully performed in children with ESRD caused by severe lower urinary tract dysfunction by making a practice of good urinary drainage using clean intermittent catheterization and augmentation cystoplasty prior to RT.
Many efforts to rescue children with ESRD by many pediatric nephrologists and transplant surgeons have resulted in remarkable accomplishments in pediatric RT.

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Cyclosporine (CsA) has been commonly used in treating steroid dependent (SDNS) and steroid-resistant (SRNS) nephrotic syndrome in children because of its great efficacy.
A long period of CsA treatment is required to maintain a long-term remission, since the discontinuation of this treatment often leads to relapses. At the present time, there is a major topic of debate about chronic cyclosporine-induced nephropathy (CsAN).
According to our retrospective study, “long-term CsA administration : more than 3 years” and “large cumulative CsA dosage : over 5g/kg” could be risk factors of CsAN in children with NS, especially irreversible CsAN : tubulointerstitial lesions. On the other hand, reversible CsAN : cyclosporine A-associated arteriolopathy (CAA) without irreversible tubulointerstitial lesions, was recognized in 3 patients treated with CsA less than 3 years (23-31 months).
Therefore, alternative treatment within 2-3 years from starting CsA administration is necessary to prevent irreversible CsAN. Our data suggest that the introduction of CsA treatment for young children with NS should be strictly limited in regard of the term of CsA treatment and cumulative dosage.

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There is no established treatment for intractable primary focal segmental glomerulosclerosis (FSGS). Recently plasma exchange and low-density lipoprotein apheresis were added to the treatment regimen. This report documents a case of 11-year boy with intractable primary FSGS who could achieve remission after the intensive treatment with plasma exchange and intravenous pulse methylprednisolone. He experienced frequent relapses despite the treatment with high-dose CsA. However, the dose of oral prednisone could be reduced after correction of hypercholesterolemia by the initiation of pravastatin.
The case indicates that correction of hyperlipidemia by plasma exchange and antihyperlipidemic agents might play a favorable role in altered response to conventional therapy, such as corticosteroid or CsA, for the patient with primary FSGS.

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We report a case of reversible posterior leukoencephalopathy syndrome (RPLS) with nephrotic syndrome (NS). The patient, an 8-year-old girl, was diagnosed with NS in October, 2002. She was administered 2 mg/kg/day of prednisolone (PSL) for 4 weeks, but did not achieve remission. She was therefore considered to have steroid-resistant NS, and was referred to our hospital. When admitted to our hospital, she had general edema and had marked abdominal distension due to ascites. Her body weight increased 5 kg than usual, and she had massive proteinuria (11 g/day), hypoproteinemia (4.3 g/dl) and hypoalbuminemia (2.3 g/dl). Her blood pressure was 120/88 mmHg, and other vital signs were normal and stable. We started cyclosporine (CyA) and PSL. Two days later, she had a generalized tonic-clonic seizure and exhibited altered mental functioning, but cortical blindness and other visual abnormalities did not appear. White-matter abnormalities in the left posterior parietal-occipital and right parietal regions of the brain were noted on Fluid-attenuated Inversion Recovery (FLAIR) MR Imaging. We stopped CyA and started an antihypertensive agent immediately, and she subsequently improved by degrees, and signs of neurological abnormality disappeared within 5 days. We also administered methylprednisolone pulse therapy (MPT) and cyclophosphamide (2 mg/kg/day for 12 weeks). The degree of proteinuria decreased after MPT, and general edema disappeared. She presently exhibits steroid-dependent NS, but has no neurological damage.
Symptoms of RPLS are headache, altered mental functioning, seizures, cortical blindness, and other visual disturbances, with hypertension. Bilateral white-matter abnormalities in the posterior regions of the cerebral hemispheres were noted on CT and MRI studies. There are reports that CyA has neurological side effects in up to 40% of patients, with RPLS the most serious of them. Neurotoxicity is more frequent with high CyA levels, but may occur within the therapeutic range. It has been reported that median time from initiation of CyA to onset of RPLS is 14 days, but it was only 2 days in our case. At the onset of neurological abnormalities in our case, it was difficult to distinguish watershed-infarction from RPLS because of early onset after the administration of CyA. However, since neurological signs resolved completely and high-signal lesions on MRI disappeared completely, we made a final diagnosis of RPLS.
RPLS may develop earlier after initiation of CyA than previously reported. It is thus necessary to monitor for RPLS at all times during administration of CyA.

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The pharmacokinetic study of mizoribine was conducted in 6 cases of child-onset renal diseases with normal renal function. The profile of the serum and urinary concentrations of mizoribine was determined. Mizoribine at daily dose of 60 mg to 250 mg (3.6∼5.0 mg/kg/day) was orally given divided into two doses. Pharmacokinetic parameters for mizoribine estimated by concentration-time profiles. Obtained pharmacokinetic values were : Tmax 2.78±0.95 hours, mean peak blood level (Cmax) of mizoribine 0.67±0.16μg/ml, T 1/2 2.12±0.51 hours, AUC 3.76±1.15μg · h/ml, cumulative urinary excretion 38.6±9.6%.
parameters obtained in the present study seemed to be useful for mizoribine treatment of patients with child-onset renal diseases.

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We report a 4-years-old girl with Alport syndrome as an acute onset of acute nephritic syndrome. She was referred to our hospital for further examination of edema, severe proteinuria and macrohematuria, 7 days after onset. These symptoms except for microhematuria were improved gradually by bed rest, restriction of salt and water intake, anticoagulant therapy. On renal biopsy, there was no deposit of IgA on immunofluorescence microscopic examination. Light microscopy with periodic acid-Schiff (PAS) stain showed mild mesangial proliferation. On electron microscopic examination, glomerular basement membrane appeared segmental thickness and thinness. Glomerular basement membrane revealed no staining for α 5 chain of collagen IV. She was diagnosed as Alport syndrome.
Acute nephritic syndrome is characterized clinically by sudden-onset proteinuria and/or hematuria. Most cases of acute nephritic syndrome are caused by poststreptococcal acute glomerulonephritis and acute onset/exacerbation of chronic glomerulonephritis. Based on our experience, it is important that Alport syndrome can be one cause of acute nephritic syndrome.

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We report two patients with ANCA associated vasculitis. They presented with renal insufficiency and respiratory distress because of pulmonary hemorrhage, and were seropositive for MPO-ANCA. The histological findings showed pauci-immune crescentic glomerulonephritis. So they were diagnosed as ANCA associated vasculitis.
Case 1 was a 7-year-old female. She was treated with methylprednisolone pulse therapy and followed by oral cyclophosphamide, prednisolone, azathioprine and dipyridamole. However she developed end-stage renal failure after four years, so she has been receiving peritoneal dialysis since then.
Case 2 was a 6-year-old female. She was treated with peritoneal dialysis for acute renal failure and methylprednisolone pulse therapy followed by oral prednisolone for respiratory distress. The pulmonary hemorrhage and the respiratory insufficiency improved. But after several days, pulmonary hemorrhage relapsed, again. At that time, methylprednisolone pulse therapy was non effective and respiratory distress was more severe. So we decided to perform plasma exchange therapy and it was so effective that pulmonary hemorrhage had completely improved.
In conclusion, prognosis of renal survival in ANCA associated vasculitis is still bad but mortality is not so high in pediatric patients. When primary disease is not improved by steroid and immunosuppressive therapy, plasma exchange may be effective for the disease.

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This is a case of a 4-year-old boy having nephrotic syndrome with peritonitis. He had a sudden of bloody vomit and abdominal pain, and it was suspected intussusception. In emergency operation, only finding was the ascites. The labolatory finding included proteinuria, hypoproteinemia, hypercholesterolemia and edema. Also the blood culture showed the presence of Strept. pneumoniae. Consequently we diagnosed him nephrotic syndrome with peritonitis caused by Strept. pneumoniae. Postoperatively he was treated with steroid and well responded.

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Acute glomerulonephritis (AGN) usually develops after the contraction of an infectious disease, including group A streptococcal infections. Typical patients present with a triad of signs and symptoms: edema, hypertension and hematuria. When evidence of a recent streptococcal infection and hypocomplementemia are present, a diagnosis of AGN is usually made and a renal biopsy is not ordinarily indicated. However, children with AGN have been reported to present with severe systemic manifestations of the disease but without significant urinary abnormalities. This type of AGN is called AGN with minimal urinary abnormalities. We report here an 11 year old boy who presented with abdominal pain, dyspnea, edema, and hypertension without urinary abnormalities. A renal biopsy was performed, and the boy was diagnosed as having AGN with minimal urinary abnormalities. Here, we describe his clinical course and the details of the renal histological findings. A differential diagnosis of edema and hypertension without urinary abnormalities should include AGN, and the measurement of serum complement activity is a useful screening test. A renal biopsy is of diagnostic significance and is justifiable for the diagnosis of AGN with minimal urinary abnormalities.

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The solitary kidney is generally considered as a contraindication for the percutaneous renal biopsy. However, renal biopsy is required for a definitive diagnosis and a proper treatment even in the patients with a solitary kidney when they have renal insufficiency or glomerulonephritis. Percutaneous renal biopsy is routinely performed for a transplanted kidney, a solitary functioning kidney. In addition, it was reported that the risk of complications at percutaneous renal biopsy is not higher than that at open biopsy. We had a 15-year-old boy with right solitary kidney who was referred to Yamagata University Hospital for further examination of proteinuria pointed out at urinary screening program. He gradually deteriorated in his renal function and we performed percutaneous renal biopsy after an informed consent was obtained. He complicated with only a little hematoma, which did not require a significant intervention. The renal specimen revealed tubular atrophy and interstitial fibrosis due to unknown causes, consistent with chronic tubulointerstitial nephritis.
Percutaneous renal biopsy is not a contraindication even for a solitary kidney if the patients are not complicated with severe hypertension and coagulation disorders and experienced operators would perform the procedure.

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We did a nation-wide survey on patients less than 15 years of age with pediatric chronic end-stage renal disease (ESRD) in Japan for the five years between year 1998 to 2002. The number of patients newly introduced to renal replacement therapy was approximately 60 per year and the incidence rate for five years was 108 (36.5%) at age 0-4 years, 52 (17.6%) at age 5-9 years and 136 (45.9%) at age 10-14 years. The annual incidence rate per million population was lowest in the 0-4 year group, followed by the 5-9 year group, and highest at 10-14 years. However, in year 2002, the incidence rate was higher at 0-4 years than any other age, which should be noted. Male patients had a higher incidence rate than females. The major diseases causing ESRD were renal hypoplasia/dysplasia and focal segmental glomerulosclerosis, with a decrease in focal segmental glomerulosclerosis. 13 patients received preemptive renal transplants. Of the remaining 280 patients, 250 (89.3%) received peritoneal dialysis and 30 (10.7%) underwent hemodialysis. The renal transplant rate by Kaplan-Meier method was 4.3% during the year the replacement therapy of ERSD had been initiated, 29.8% by two years later and 41.3% by four years later. All transplants were from living related donors with the exception of one patient. The survival rates by Kaplan-Meier method were 98.2% during the year of initiation of replacement therapy of ERSD, and 91.1% by four years later. The major causes of death were cardiovascular diseases and infections.

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We report a 7-year-old girl with IgA nephropathy presented with FSGS-like podocyte hypertrophy. She had microhematuria and nephrotic-range proteinuria. The initial renal biopsy specimens showed diffuse mesangial proliferation, endocapillary proliferation, double contours of capillary walls, fibrocellular crescent formation, and podocyte hypertrophy resembling FSGS.
Immunofluorescence studies demonstrated a predominant deposition of IgA along capillary walls. On electron microscopy, the deposits in the paramesangial and subendothelial areas were found. She was diagnosed as IgA nephropathy and treated with intravenous methylprednisolone pulse therapy. Thereafter the combined therapy of prednisolone, mizoribine, warfarin and dipyridamole was started. Proteinuria was reduced and serum total protein increased gradually. We performed the second biopsy of the kidney 6 months after initiation of the therapy. The second biopsy showed a moderate improvement of FSGS-like podocyte hypertrophy.

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The recent routine use of maternal ultrasonography has resulted in increasing detections of congenital hydronephrosis. The conservative management of patients with asymptomatic hydronephrosis is usually recommended because it tends to improve spontaneously. We report two cases of neonate who suffered from anuric renal failure associated with bilateral hydronephrosis secondary to posterior urethral valve or ureterovesical junction obstruction. The causes of renal insufficiency in two cases were presumebly post-renal origin because of immediate recovery after urinary drainage.
Therefore, careful follow-up in case of the neonate with bilateral hydronephrosis which might cause acute renal failure rarely in combination with urolithiasis must be needed.

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Cyclic neutropenia (CN) is a rare disease, primarily affecting neutrophil production. Autosomal dominant and sporadic cases of CN are caused by mutations in the gene for neutrophil elastase. A 16-year-old girl has recurrent aphthous ulceration and hematuria occurring with these episodes. The clinical features and serial peripheral blood studies establish a diagnosis of CN at the age of one month. Hematuria shows waxing and waning at times of oral ulceration and neutropenia. Serum immunoglobulins are elevated, with a disproportionate elevation of IgA. The kidney tissue specimens show diffuse mesangial involvement with mesangial IgA and C 3 deposition and electron dense deposits in the mesangium, consistent with IgA nephropathy. Her renal function remains well with oral prednisolone therapy. Patients with CN increase the likelihood of significant mucosal infection and therefore the probability of overt and symptomatic IgA nephropathy. A long-term administration of granulocyte-colony stimulating factor may immunologically contribute to the development of glomerular diseases.

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[in Japanese]

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[in Japanese]

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