Osamu Uemura

PCR on cerebrospinal fluid to show influenza-associated acute encephalopathy or encephalitis

BACKGROUND Except for Reyes syndrome, influenza-associated acute encephalopathy or encephalitis is not universally recognised. We did a multicentre study of laboratory and clinical data for patients with influenza-associated acute encephalopathy or encephalitis. METHODS In Nagoya, Japan, ten patients with acute encephalopathy or encephalitis associated with influenza-like illness were admitted to our hospitals between April, 1996, and March, 1997. We collected clinical, laboratory and serological data and assessed cerebrospinal fluid samples by PCR for influenza A and B. FINDINGS Seven patients, aged 22 months to 4 years, had evidence of recent influenza infection, six with type-A/Hong Kong (H3N2) and one with type B. The first sign in the central nervous system appeared within 2 days of fever in all but one patient. The first sign of involvement of the central nervous system was generalised convulsions in all patients. Two patients died, one had sequelae, and four survived without sequelae. PCR for influenza type A was positive for five patients. INTERPRETATION The results of PCR suggest that at least part of the influenza type A genome existed in the central nervous system. Influenza-associated acute encephalopathy or encephalitis in young children deserves wider recognition.

Age, gender, and body length effects on reference serum creatinine levels determined by an enzymatic method in Japanese children : a multicenter study

BackgroundEnzymatic methods have recently been used to measure creatinine (Cr) instead of the Jaffe method. Therefore, it is necessary to determine the reference serum Cr value for these enzymatic methods to evaluate renal function in Japanese children.MethodsTo determine reference values of serum Cr in Japanese children, 1151 children (517 male, 634 female) aged between 1 month and 18 years had their serum Cr values measured by an enzymatic method. To be included in the study the children had to be without kidney disease, urogenital disease, infectious disease, inflammatory disease, dehydration, muscular disease, anomaly syndrome, cardiovascular disease, malignant disease, hypertension, liver or pancreas disease, or pregnancy.ResultsThe medians of reference values increased gradually with age, i.e., 0.30 mg/dl at 4 years old and 0.41 mg/dl at 10 years old. In adolescence, they increased significantly more rapidly in males than in females. We found a linear regression equation capable of estimating the reference value of serum Cr in children aged 2–11 years, and quintic regression equations capable of estimating the reference values of serum Cr in male and female children of all ages.ConclusionThe reference serum Cr levels determined by an enzymatic method related to age, gender, and body length, and our linear and polynomial equations showing the relationship between body length and serum Cr level will be applicable for screening of renal function in Asian as well as Japanese children.

Analysis of genetic and predisposing factors in Japanese patients with atypical hemolytic uremic syndrome

Hemolytic uremic syndrome (HUS) is characterized by microangiopathic hemolytic anemia, thrombocytopenia, and renal impairment. Approximately 10% of cases are classified as atypical due to the absence of Shiga toxin-producing bacteria as a trigger. Uncontrolled activation of the complement system plays a role in the pathogenesis of atypical HUS (aHUS). Although many genetic studies on aHUS have been published in recent years, only limited data has been gathered in Asian countries. We analyzed the genetic variants of 6 candidate genes and the gene deletion in complement factor H (CFH) and CFH-related genes, examined the prevalence of CFH autoantibodies and evaluated the genotype-phenotype relationship in 10 Japanese patients with aHUS. We identified 7 causative or potentially causative mutations in CFH (p.R1215Q), C3 (p.R425C, p.S562L, and p.I1157T), membrane cofactor protein (p.Y189D and p.A359V) and thrombomodulin (p.T500M) in 8 out of 10 patients. All 7 of the mutations were heterozygous and four of them were novel. Two patients carried CFH p.R1215Q and 3 other patients carried C3 p.I1157T. One patient had 2 causative mutations in different genes. One patient was a compound heterozygote of the 2 MCP mutations. The patients carrying mutations in CFH or C3 had a high frequency of relapse and a worse prognosis. One patient had CFH autoantibodies. The present study identified the cause of aHUS in 9 out of 10 Japanese patients. Since the phenotype-genotype correlation of aHUS has clinical significance in predicting renal recovery and transplant outcome, a comprehensively accurate assessment of molecular variation would be necessary for the proper management of aHUS patients in Japan.

Pre-dialysis chronic kidney disease in children: results of a nationwide survey in Japan

BACKGROUND Chronic kidney disease (CKD) in children is a progressive and intractable condition that may severely impair the childs growth, development and quality of life. Epidemiological information on pediatric CKD, particularly in Asians, is scant. METHODS We conducted a nationwide, population-based survey of Japanese children aged 3 months to 15 years with pre-dialysis CKD to examine the prevalence of pediatric CKD in Japan. CKD was classified according to newly established criteria derived from reference serum creatinine levels in Japanese children. Surveys were sent to 1190 institutions across Japan to report on cases of pediatric CKD managed as of 1 April 2010. RESULTS A total of 925 institutions (77.7%) responded. Information on 447 children was collected. When subdivided according to our diagnostic criteria, 70.5% of children had stage 3 CKD, 23.9% stage 4 and 5.6% stage 5. The estimated prevalence of Japanese children with CKD was 2.98 cases/100,000 children. Of 407 CKD cases with non-glomerular disease, 278 (68.3%) had congenital anomalies of the kidney and urinary tract (CAKUT). The newly established criteria showed good validity compared with existing criteria, including the abbreviated Schwartz equation. CONCLUSIONS Findings from the first nationwide survey of pre-dialysis CKD in Asian children indicate that the prevalence of stage 3-5 CKD in children in Japan aged 3 months to 15 years is 2.98 cases/100,000 children. Most children with CKD presented with non-glomerular disease, most frequently CAKUT. Improved management of CAKUT, including renoprotective treatment and urological intervention, is required.

CKD Clinical Practice Guidebook. The essence of treatment for CKD patients.

1. Chronic kidney disease (CKD) is defined either as a kidney disorder (proteinuria, etc.) or as decreased kidney function with GFR (glomerular filtration rate) less than 60 mL/min/1.73 m lasting for 3 months or longer. 2. Estimated GFR (eGFR) is calculated using the following formula: eGFR (mL/min/1.73 m) = 194 9 Cr 9 Age (additional multiplication by 0.739 for women). 3. CKD is a critical risk factor for the development of CVD (cardiovascular disease) as well as ESKD (endstage kidney disease). 4. A CKD patient should be managed by a multidisciplinary approach in collaboration between primary care physicians and nephrologists. 5. It is desirable that the following cases are referred to nephrologists: (1) proteinuria of 0.5 g/g creatinine or greater, or 2? or greater; (2) eGFR less than 50 mL/min/1.73 m; (3) positive (1? or greater) for both proteinuria and hematuria. 6. The treatment goal of proteinuria is less than 0.5 g/g creatinine. 7. CKD management should be started with modification of lifestyle (smoking cessation, salt restriction, improvement of obesity, etc.). 8. The goal of blood pressure control is less than 130/80 mmHg and is gradually achieved. 9. Antihypertensive agents of first choice are ACE inhibitors or ARBs. A combination with other antihypertensive agents is applied as needed. 10. In the use of ACE inhibitors or ARBs, a physician should be aware of the risk of an elevation of serum creatinine level and hyperkalemia in CKD patients. 11. In diabetic nephropathy, the target level of hemoglobin A1C should be less than 6.5% in controlling the blood glucose level. 12. LDL cholesterol should be controlled below 120 mg/dL. 13. A physician should consult nephrologists when renal anemia is suspected. 14. A physician should consult nephrologists when prescription of erythropoiesis-stimulating agents or oral adsorbent is contemplated. 15. A physician should reduce the dosage or extend the administration interval depending on kidney function when administering drugs that are eliminated by the kidney. 16. Non-steroidal anti-inflammatory drugs (NSAIDs), contrast media, and dehydration are risk factors for decline in kidney function.

Age-dependent decrease in serum transforming growth factor (TGF)-beta 1 in healthy Japanese individuals; population study of serum TGF-beta 1 level in Japanese

Transforming growth factor-beta1 (TGF-β1), a multi-functional cytokine, is involved in regulating a variety of cellular activities and the serum/plasma TGF-β1 level is altered with various diseases. However, most published reports have described adult patients, and so we investigated the clinical significance of serum TGF-β1 level in pediatric patients. The diagnostic application of the measurement of serum TGF-β1 level depends critically on the control value, however, there is no information on the control value of serum TGF-β1 for children. In the present study, we determined the serum TGF-β1 level of healthy Japanese children as a control value with enzyme-linked immunosorbent assay (ELISA). The serum TGF-β1 level of children (0–14 years old) was significantly higher than that of adults (over 15 years old) (p < 0.01). Thus, it is recommended that when the serum TGF-β1 levels of patients are evaluated, they should be compared with those of age-matched controls.

Progression to end-stage kidney disease in Japanese children with chronic kidney disease: results of a nationwide prospective cohort study

BACKGROUND The risk of progressing to end-stage kidney disease (ESKD) and factors associated with progression in children with chronic kidney disease (CKD) are unclear, especially in Asian children. METHODS We started a nationwide, prospective cohort study of 447 Japanese children with pre-dialysis CKD in 2010, with follow-up in 2011. Progression to ESKD was analyzed by Kaplan-Meier analysis according to CKD stage. Cox regression analysis was used to identify risk factors for progression. RESULTS Data were analyzed for 429/447 children. Five patients died, of which four died before progression to ESKD. Fifty-two patients progressed to ESKD (median follow-up 1.49 years), including 9/315 patients with stage 3 CKD, 29/107 with Stage 4 CKD and 14/25 with Stage 5 CKD. One-year renal survival rates were 98.3, 80.0 and 40.9%, for Stages 3, 4 and 5 CKD, respectively. Risk factors for progression to ESKD included CKD stage [versus Stage 3; Stage 4: hazard ratio (HR) 11.12, 95% confidence interval (CI) 4.22-29.28, P < 0.001; Stage 5: HR 26.95, 95% CI 7.71-94.17, P < 0.001], heavy proteinuria (>2.0 g/g urine creatinine; HR 7.56, 95% CI 3.22-17.77, P < 0.001) and age ( < 2 years: HR 9.06; 95% CI 2.29-35.84, P = 0.002; after starting puberty: HR 4.88; 95% CI 1.85-12.85, P = 0.001). CONCLUSIONS In this cohort, 12.5% of children with pre-dialysis CKD progressed to ESKD with a median-follow-up of 1.49 years. Children with advanced (Stage 4/5) CKD were particularly likely to progress. To our knowledge, this is the first, nationwide, prospective cohort study of children with pre-dialysis CKD in Asia.

Determination of age-related changes in human soluble interleukin 2 receptor in body fluids of normal subjects as a control value against disease states

A highly sensitive enzyme-linked immunosorbent assay (ELISA) system was developed for human soluble interleukin-2 receptor (sIL-2R) with an ELISA-amplification system (ELAST((R))). The sensitivity of the new method was 20-fold higher than that without the amplification. Thus very low concentrations of sIL-2R in urine can be detected. With this method, serum and urine concentrations of sIL-2R were analyzed for healthy Japanese subjects with age 1-67 years. Mean sIL-2R concentrations in both serum and urine of children were significantly higher than those of adults. However, the concentrations of children showed a progressive decline to those of adults by the age of 15 years. There was no difference in the values between males and females. The results provide a control value of sIL-2R against those in disease states such as nephrotic syndrome. Since the trends in serum and urine were found to be similar, urinary sIL-2R measurement may provide sufficient information, without measuring the blood concentration.

High Prevalence of Sinusitis in Children with Henoch-Schönlein Purpura

We evaluated the prevalence and the types of infectious foci in oral as well as ear, nose, and throat diseases, and we examined incidence of renal involvement with active treatment for focal infection in children with Henoch-Schönlein Purpura. A total of 96 children who presented at Aichi Childrens Health and Medical Center and were diagnosed as having HSP were evaluated for infectious foci in the ear, nose, throat, and oral cavities. Seventy-one of 96 children (74.0%) had some type of infectious lesion, such as sinusitis or tonsillitis, and the prevalence of sinusitis was the highest (51 cases, 53.7%). In 44 HSP patients without renal involvement at the first examination, the incidence of nephritis was lower (13.6%) than in previous reports (17–54%) due to our aggressive intervention for infectious foci.

Three year outcome of childhood idiopathic nephrotic syndrome under a unified immunosuppressive protocol

This retrospective study was performed to assess the 3 year outcome of a unified protocol for childhood idiopathic nephrotic syndrome.