Precise clinicopathologic findings for application of genetic testing in pediatric kidney transplant recipients with focal segmental glomerulosclerosis/steroid-resistant nephrotic syndrome.

BACKGROUND: Establishing a molecular genetic diagnosis of focal segmental glomerulosclerosis (FSGS)/steroid-resistant nephrotic syndrome (SRNS) can be useful for predicting post-transplant recurrence. Monogenic causes are reportedly present in approximately 20-30% of patients with FSGS/SRNS. However, the characteristics of patients who are likely to have a monogenic cause remain to be determined. METHODS: Pediatric recipients with SRNS and/or biopsy-proven FSGS who underwent their first kidney transplantation at our center between 1999 and 2019 were analyzed. Patients with secondary FSGS/SRNS were excluded. The recipients were divided into three groups: familial/syndromic, presumed primary, and undetermined FSGS/SRNS. Patients who met all of the following criteria were categorized as having presumed primary FSGS/SRNS: (i) nephrotic syndrome, (ii) complete or partial remission with initial steroid therapy and/or additional immunosuppressive therapies, and (iii) diffuse foot process effacement on electron microscopy in the native kidney biopsy. All patients underwent genetic testing using next-generation sequencing. RESULTS: Twenty-four patients from 23 families were analyzed in this study. Pathogenic or likely pathogenic variants in FSGS/SRNS-related genes were identified in four of four families, zero of eight families, and 10 of 11 families with familial/syndromic, presumed primary, and undetermined FSGS/SRNS, respectively. Post-transplant recurrence only occurred in patients with presumed primary FSGS/SRNS. CONCLUSIONS: Our systematic approach based on precise clinicopathological findings including nephrotic syndrome, treatment responses, and diffuse foot process effacement might be useful to differentiate pediatric kidney transplant recipients with FSGS/SRNS who are likely to have a monogenic cause from patients who are not, and to predict post-transplant recurrence. A higher resolution version of the Graphical abstract is available as Supplementary information.

Amount and selectivity of proteinuria may predict the treatment response in post-transplant recurrence of focal segmental glomerulosclerosis: a single-center retrospective study.

BACKGROUND: Primary focal segmental glomerulosclerosis (FSGS) frequently recurs after kidney transplantation and is associated with poor graft survival. To date, few studies have investigated predictive factors for treatment responses in recurrent FSGS. METHODS: We retrospectively analyzed 16 patients who were < 16 years at the age of onset and had post-transplant recurrence of FSGS from 1993 to 2018. Patients who achieved complete remission or partial remission after initiating therapy for recurrent FSGS were defined as responders. We compared several clinical characteristics between responders and non-responders. Time to remission was also analyzed. RESULTS: Ten patients were responders, and six patients were non-responders. Univariate analysis showed that responders had a significantly lower amount of maximum proteinuria at the time of recurrence (P = 0.015) and more highly selective proteinuria (P = 0.013) than non-responders. The time to remission from initiation of therapy was 2 months (interquartile range 0.2-4.4). In all responders, except for one patient, remission was achieved within 6 months. CONCLUSIONS: Therapeutic responses may be predicted by examining the amount and selectivity of proteinuria at the time of recurrence. Further studies with larger numbers of patients are clearly required to validate these findings.

Long-term outcome of renal transplantation in childhood-onset anti-neutrophil cytoplasmic antibody-associated vasculitis.

BACKGROUND: There have been a few reports of RTx for AAV in children; however, post-transplant recurrence rate and long-term prognosis remain unclear. Here, we describe the long-term outcomes of RTx in childhood-onset AAV. METHODS: We conducted a retrospective study of children who underwent RTx for AAV between 1999 and 2017 and had a follow-up period of >2 years. RESULTS: Seven patients consisting of three children with MPA and four with RLV were analyzed. Age at Dx was 5.9 (median; range, 4.1-14.5) years. PD was instituted in all patients, and median time on dialysis was 26 (range, 14-63) months. Age at RTx was 12.8 (median; range, 8.7-16.3) years. There were no recurrences of AAV noted during the median follow-up period of 7.0 (range, 2.7-18.8) years after RTx. Graft loss occurred in one patient due to non-adherence. Estimated glomerular filtration rate of the remaining patients at the last follow-up was 73.0 (median; range, 50.7-93.9) mL/min/1.73 m2 . No malignancies and deaths occurred during the observational period. CONCLUSIONS: Our study suggests that RTx for AAV with ESRD is a potentially safe and effective treatment choice for children with AAV.

Individualized concept for the treatment of autosomal recessive polycystic kidney disease with end-stage renal disease.

Management of children with autosomal recessive polycystic kidney disease (ARPKD) who develop end-stage renal disease (ESRD) remains challenging because of concomitant liver disease. Patients with recurrent cholangitis are candidates for liver-kidney transplantation, while the treatment for patients with splenomegaly and pancytopenia due to portal hypertension is controversial. Herein, we report 7 children who were treated using an individualized treatment strategy stratified by liver disease. Two patients with recurrent cholangitis underwent sequential liver-kidney transplantation, while 4 patients with splenomegaly and pancytopenia but without recurrent cholangitis underwent splenectomy followed by isolated kidney transplantation. The remaining patient, who did not have cholangitis and pancytopenia, underwent isolated kidney transplantation. Blood cell counts were normalized after splenectomy was performed at the median age of 8.7 (range, 7.4-11.7) years. Kidney transplantation was performed at the median age of 8.8 (range, 1.9-14.7) years in all patients. Overwhelming post-splenectomy infections and cholangitis did not occur during the median follow-up period of 6.3 (range, 1.0-13.2) years. The estimated glomerular filtration rate at the last follow-up was 53 (range, 35-107) mL/min/1.73 m2 . No graft loss occurred. Our individualized treatment strategy stratified by recurrent cholangitis and pancytopenia can be a feasible strategy for children with ARPKD who develop ESRD and warrants further evaluation.

Renal hypoplasia can be the cause of membranous nephropathy-like lesions.

BACKGROUND: Renal hypoplasia (RH) is the most common cause of chronic kidney disease in children. In cases of RH, proteinuria is often induced by glomerular hypertrophy and hyperfiltration that is commonly associated with focal segmental glomerulosclerosis. This study reports the first case series of a possible association between RH and membranous nephropathy (MN). METHODS: Of the 168 children with RH who visited our department between 1999 and 2017, five with overt proteinuria (≥ 1 g/gCr) underwent renal biopsy. We retrospectively reviewed the medical charts and analyzed biopsy specimens using light microscopy (LM), immunofluorescence (IF), and electron microscopy. RESULTS: The five children (four boys and one girl) had a median age of 5.5 years at the time of renal biopsy. The median proteinuria was 4.23 g/gCr (range 1.46-14.25), median serum albumin, 2.9 g/dL (range 2.3-3.7), and median estimated glomerular filtration rate, 59.7 mL/min/1.73 m2 (range 36.7-103.6). LM showed segmental spike formation and mesangial hypercellularity and IF study showed segmental granular immunoglobulin G (IgG) staining (IgG1 and IgG3 dominant) along the capillary loops in all five patients. Electron-dense deposits were observed in the subepithelial and mesangial areas. Thus, the pathological studies showed MN-like lesions in all patients. CONCLUSION: Our study suggests that RH can be the cause of MN-like lesions.

[Pathological Findings of Chronic Effects Observed in the Kidneys Exposed to Antineoplastic Agents in Two Adolescent Patients].

Cisplatin and ifosfamide are well-known nephrotoxic agents that can cause acute and chronic glomerular and/or tubular toxicity. We examined 2 adolescent patients who were receiving cisplatin and ifosfamide treatments. Pathological findings of patient 1 showed acute tubular necrosis-like patchy injury. Tubulointerstitial nephrosis and glomerular sclerosing were revealed in patient 2. These findings were consistent with the known damages induced by cisplatin and ifosfamide. Proteinuria and mild decline of eGFR were noticed after more than 10 months after the completion of the treatment. It is important to monitor such consequences in long-term follow up. Adult based medical services are required for childhood and adolescent cancer survivors.

A grading system that predicts the risk of dialysis induction in IgA nephropathy patients based on the combination of the clinical and histological severity.

Histological classification is essential in the clinical management of immunoglobulin A nephropathy (IgAN). However, there are limitations in predicting the prognosis of IgAN based on histological information alone, which suggests the need for better prognostic models. Therefore, we defined a prognostic model by combining the grade of clinical severity with the histological grading system by the following processes. We included 270 patients and explored the clinical variables associated with progression to end-stage renal disease (ESRD). Then, we created a predictive clinical grading system and defined the risk grades for dialysis induction by a combination of the clinical grade (CG) and the histological grade (HG). A logistic regression analysis revealed that the 24-h urinary protein excretion (UPE) and the estimated glomerular filtration rate (eGFR) were significant independent variables. We selected UPE of 0.5 g/day and eGFR of 60 ml/min/1.73 m2 as the threshold values for the classification of CG. The risk of progression to ESRD of patients with CG II and III was significantly higher than that of patients with CG I. The patients were then re-classified into nine compartments based on the combination of CG and HG. Furthermore, the nine compartments were grouped into four risk groups. The risk of ESRD in the moderate, high, and super-high-risk groups was significantly higher than that in the low-risk group. Herein, we are giving a detailed description of our grading system for IgA nephropathy that predicted the risk of dialysis based on the combination of CG and HG.

Biallelic Mutations in Nuclear Pore Complex Subunit NUP107 Cause Early-Childhood-Onset Steroid-Resistant Nephrotic Syndrome.

The nuclear pore complex (NPC) is a huge protein complex embedded in the nuclear envelope. It has central functions in nucleocytoplasmic transport, nuclear framework, and gene regulation. Nucleoporin 107 kDa (NUP107) is a component of the NPC central scaffold and is an essential protein in all eukaryotic cells. Here, we report on biallelic NUP107 mutations in nine affected individuals who are from five unrelated families and show early-onset steroid-resistant nephrotic syndrome (SRNS). These individuals have pathologically focal segmental glomerulosclerosis, a condition that leads to end-stage renal disease with high frequency. NUP107 is ubiquitously expressed, including in glomerular podocytes. Three of four NUP107 mutations detected in the affected individuals hamper NUP107 binding to NUP133 (nucleoporin 133 kDa) and NUP107 incorporation into NPCs in vitro. Zebrafish with nup107 knockdown generated by morpholino oligonucleotides displayed hypoplastic glomerulus structures and abnormal podocyte foot processes, thereby mimicking the pathological changes seen in the kidneys of the SRNS individuals with NUP107 mutations. Considering the unique properties of the podocyte (highly differentiated foot-process architecture and slit membrane and the inability to regenerate), we propose a "podocyte-injury model" as the pathomechanism for SRNS due to biallelic NUP107 mutations.

Predominant but silent C1q deposits in mesangium on transplanted kidneys - long-term observational study.

BACKGROUND: C1q nephropathy (C1qN) was first described as glomerular disease characterized by predominant meangial C1q deposits in patients with proteinuria and no evidence of systemic lupus erythematosus. Several studies, however, revealed the clinical heterogeneity of C1qN, showing some cases with normal urinalysis. To confirm the existence of cases with predominant mesangial C1q deposits and negative or mild proteinuria and/or hematuria, we investigated renal graft biopsy specimens showing negative to mild proteinuria (less than or equal to 1+ by dip stick test) and/or hematuria. METHODS: Eligible participants were kidney transplant cases who corresponded to the criteria for C1qN and were followed more than 10 years. Their medical records were reviewed to determine the age at detection of predominant mesangial C1q deposits, gender, original renal disease and reason for renal graft biopsy, blood pressure, degree of proteinuria and hematuria, and serum creatinine levels. RESULTS: From 414 cases in adults and children, five pediatric patients (the male to female ratio, 1:1.5) were eligible. At the time when predominant mesangial C1q deposits were detected, 2 cases presented with mild proteinuria without hematuria, but the other 3 cases showed normal urinalysis. Light microscopy revealed minor glomerular abnormality in all the cases. Immunofluorescent study showed predominant mesangial C1q deposits with IgG, IgM and C3 in all cases. All selected specimens presented electron dense-depos in the mesangium. Ten years later from the detection, 2 cases continued to be normal urinalysis and 3 cases had mild proteinuria without hematuria. During this follow-up period, no cases presented with persistent proteinuria and/or hematuria greater than or equal to 2+ by dip stick test. And no cases developed systemic lupus erythematosus. Follow-up renal graft biopsies were performed once in 2 cases 8 years later from the detection. They showed minor glomerular abnormalities. C1q deposit disappeared in one case. In another case, immunofluorescent study was not examined. CONCLUSIONS: This long-term observational study on transplanted kidneys confirms the existence of cases with predominant but silent C1q deposits in the mesangium who have negative or mild proteinuria.

Analysis of the genes responsible for steroid-resistant nephrotic syndrome and/or focal segmental glomerulosclerosis in Japanese patients by whole-exome sequencing analysis.

Steroid-resistant nephrotic syndrome (SRNS) represents glomerular disease resulting from a number of different etiologies leading to focal segmental glomerulosclerosis (FSGS). Recently, many genes causing SRNS/FSGS have been identified. These genes encode the proteins associated with the formation and/or maintenance of glomerular filtration barrier. Next-generation sequencing is used to analyze large numbers of genes at lower costs. To identify the genetic background of Japanese patients, we studied 26 disease-causing genes using whole-exome sequencing analysis in 24 patients with SRNS and/or FSGS from 22 different Japanese families. We finally found eight causative gene mutations, four recessive and four dominant gene mutations, including three novel mutations, in six patients from five different families, and one novel predisposing mutation in two patients from two different families. Causative gene mutations have only been identified in ~20% of families and further analysis is necessary to identify the unknown disease-causing gene. Identification of the disease-causing gene would support clinical practices, including the diagnosis, understanding of pathogenesis and treatment.

New-onset diabetes after renal transplantation in a patient with a novel HNF1B mutation.

CAKUT are the most frequent causes of ESRD in children. Mutations in the gene encoding HNF1B, a transcription factor involved in organ development and maintenance, cause a multisystem disorder that includes CAKUT, diabetes, and liver dysfunction. Here, we describe the case of a patient with renal hypodysplasia who developed NODAT presenting with liver dysfunction. The NODAT was initially thought to be steroid and FK related. However, based on the patient's clinical features, including renal hypodysplasia and recurrent elevations of transaminase, screening for an HNF1B mutation was performed. Direct sequencing identified a novel splicing mutation of HNF1B, designated c.344 + 2T>C. Because CAKUT is the leading cause of ESRD in children and HNF1B mutations can cause both renal hypodysplasia and diabetes, HNF1B mutations may account for a portion of the cases of NODAT in pediatric patients who have undergone kidney transplantation. NODAT is a serious and major complication of solid organ transplantation and is associated with reduced graft survival. Therefore, for the appropriate management of kidney transplantation, screening for HNF1B mutations should be considered in pediatric patients with transplants caused by CAKUT who develop NODAT and show extra-renal symptoms.

Transition of adolescent and young adult patients with childhood-onset chronic kidney disease from pediatric to adult renal services: a nationwide survey in Japan.

BACKGROUND: Transition of adolescent and young adult (AYA) patients with childhood-onset chronic kidney diseases (C-CKD) from pediatric to adult renal services has received increasing attention. However, information on transition of Japanese patients with C-CKD is limited. METHODS: The Transition Medicine Working Group, in collaboration with the Japanese Society for Nephrology, the Japanese Society for Pediatric Nephrology and the Japanese Society of Pediatric Urology, conducted a retrospective cross-sectional study in 2014 on issues concerning the transition of Japanese patients with C-CKD. RESULTS: Few institutions in Japan had transition programs and/or transition coordinators for patients with C-CKD. Refusal to transfer by patients or their families, lack of concern about transition and inability to decide on transfer were common reasons for non-transfer of patients still followed by pediatric renal services. Around 25 % of patients who had ended or interrupted follow-up by pediatric renal services presented to adult renal services because of symptoms associated with C-CKD. Patients with various types of childhood-onset nephrourological diseases were transferred from pediatric to adult renal services. IgA nephropathy, minimal change nephrotic syndrome and congenital anomalies of the kidney and urinary tract were the most frequent primary kidney diseases in adult patients with C-CKD. CONCLUSION: These survey results indicate the need for introduction of transitional care for Japanese AYA patients with C-CKD. Consensus guidelines for the optimal clinical management of AYA patients with C-CKD are required to ensure the continuity of care from child to adult renal services.

Beta-2 microglobulin-based equation for estimating glomerular filtration rates in Japanese children and adolescents.

BACKGROUND: Although the creatinine (Cr)-based equation is widely used for estimating glomerular filtration rate (GFR), this equation is not ideally suited for children with low body weight or aged <2 years. Therefore, we established a new equation using serum beta-2 microglobulin (ß2MG) levels for Japanese children with chronic kidney disease (CKD). METHODS: Inulin clearance and standardized serum ß2MG and Cr levels were measured in 137 CKD patients aged 1 month-18 years. Using the previously established normal ß2MG levels, Cr reference values, and Cr-based equation of estimated GFR (eGFR) in Japanese children, receiver operating characteristics (ROC) analyses were performed to compare the diagnostic accuracy between ß2MG- and Cr-based estimations of GFR. RESULTS: Serum ß2MG concentrations progressively increased as GFRs reduced. The correlation coefficients between GFR and ß2MG, and between GFR and 1/ß2MG were -0.74 (p < 0.001) and 0.86 (p < 0.001), respectively. The inulin clearance, as based on 1/serum ß2MG expression, in pediatric CKD patients resulted in the equation: inulin GFR (mL/min/1.73 m(2)) = 149.0 × 1/serum ß2MG (mg/L) +9.15. ROC analyses indicated that the ability of serum ß2MG-based GFR <95 mL/min/1.73 m(2) in children >2 years was better than the Cr-based estimated GFR (areas under the ROC curve 0.960 vs. 0.948, respectively). CONCLUSION: The new ß2MG-based eGFR formula is useful for clinical screening of renal function in Japanese children and adolescents, and measurement of serum ß2MG and Cr levels as markers for predicting glomerular function may aid the early detection of mildly reduced GFR in this population.

Reference glomerular filtration rate levels in Japanese children: using the creatinine and cystatin C based estimated glomerular filtration rate.

BACKGROUND: The present study was performed to determine the reference values of glomerular filtration rate (GFR) in children by age using the new eGFR equations derived from serum creatinine (Cr) and cystatine C (cysC). METHODS: A total of 1137 children (509 males and 628 females) between the ages of 3 months and 16 years presenting at our facilities between 2008 and 2009 without diseases affecting the renal function were included in this study as in our previous reports for reference values of serum Cr and cysC. We calculated eGFR with the Cr based equation in children aged 2-16 years, and with the cysC based equation in those aged 3-23 months, and determined the reference values of GFR in Japanese children by each age group. RESULTS: We reviewed the median, 2.5 and 97.5 percentile of GFR reference value in each age group. The medians of reference GFRs are 91.7, 98.5, 106.3, and 113.1 mL/min/1.73 m(2) in children aged 3-5, 6-11, 12-17, and 18 months-16 years, respectively. CONCLUSION: We determined the normal reference values of GFR in children. It is important for pediatricians who examine pediatric chronic kidney disease patients to know the values of normal renal function.

Decreased glomerular filtration as the primary factor of elevated circulating suPAR levels in focal segmental glomerulosclerosis.

BACKGROUND: Circulating factor(s) has been thought to be the underlying cause of focal segmental glomerulosclerosis (FSGS), and recent studies foster this idea by demonstrating increased soluble urokinase receptor (suPAR) levels in the serum of FSGS patients. METHODS: To explore the possible contribution of suPAR in FSGS pathogenesis, we analyzed serum suPAR levels in 17 patients with FSGS and compared them with those in patients with steroid-sensitive nephrotic syndrome, chronic glomerulonephritis, or non-glomerular kidney diseases. RESULTS: Serum suPAR levels in patients with FSGS were higher than those in patients with steroid-sensitive nephrotic syndrome or chronic glomerulonephritis, but not higher than those in patients with non-glomerular kidney diseases. suPAR levels negatively correlate with estimated glomerular filtration rate and were decreased after renal transplantation in patients with FSGS as well as in those with non-glomerular kidney diseases. Furthermore, 6 FSGS patients with post-transplant recurrence demonstrated that suPAR levels were not high during the recurrence. CONCLUSIONS: Based on our results, elevated suPAR levels in FSGS patients were attributed mainly to decreased glomerular filtration. These data warrant further analysis for involvement of possible circulating factor(s) in FSGS pathogenesis.

Final adult height in kidney recipients who underwent highly successful transplantation as children: a single-center experience.

BACKGROUND: Achieving a normal final adult height (FH) remains a challenge in the field of pediatric kidney transplantation (KTx). To examine the optimal approach to assuring normal FH following KTx, we retrospectively examined the post-transplant growth and FH of pediatric KTx recipients. METHODS: Since the relevant factors affecting the FH of children following KTx are multifactorial and notably complex, KTx recipients with persistent good graft function and successful steroid minimization until FH attainment were selected for this study. RESULTS: Thirteen patients were enrolled in this study. The mean estimated glomerular filtration rate was 72.1 ± 15.3 ml/min/1.73 m(2), and the mean corticosteroid dose was 0.05 ± 0.05 mg/kg on alternate days at the time of FH attainment. Despite highly successful KTx, four (30.8 %) patients (one who underwent KTx before puberty and three during puberty) showed a decrease in the height standard deviation score (hSDS) from the time of KTx until FH attainment. Moreover, of these, two male patients had an FH with an SD <-2. CONCLUSION: FH remained suboptimal despite highly successful KTx. Not only highly successful KTx but also further treatment such as steroid avoidance, early steroid withdrawal or using rhGH might be necessary to assure a normal FH in some pubertal patients.

Plasma homocysteine and folate levels and dietary folate intake in adolescents and young adults who underwent kidney transplantation during childhood.

BACKGROUND: Hyperhomocysteinemia (hyper-Hcy) is an important and reversible cardiovascular disease risk factor. We examined the prevalence of hyper-Hcy, plasma folate levels, and dietary folate intake in adolescents and young adults who had undergone kidney transplantation during childhood to assess the necessity for managing dietary folate. METHODS: This cross-sectional study was performed in 89 kidney transplant recipients (age at kidney transplantation: 12.6 ± 4.1 years; age during study: 21.2 ± 5.5 years). Hyper-Hcy and plasma folate deficiency were defined as plasma homocysteine (Hcy) >15 nmol/ml and plasma folate <3.0 ng/ml, respectively. RESULTS: Of the patients, 60 (67.4 %) had hyper-Hcy and 14 (15.7 %) had plasma folate deficiency. Plasma homocysteine levels correlated negatively with estimated glomerular filtration rate (eGFR; r = -0.565, p < 0.01) and plasma folate levels (r = -0.434, p < 0.01). For determinants of plasma homocysteine levels, a priori selected variables included kind of calcineurin inhibitor, age at kidney transplantation, pretransplant duration of dialysis, time since transplantation, age at examination, eGFR, and plasma folate. Stepwise multiple linear regression analysis revealed eGFR and plasma folate levels as significant independent variables influencing plasma homocysteine levels. Dietary folate intake in 11 of 16 patients (66.8 %) with eGFR ≥ 60 ml/min/1.73 m(2) was below the recommended dietary allowance for Japanese. CONCLUSIONS: The prevalence of hyper-Hcy and plasma folate deficiency, as well as the low dietary folate intake, suggest that dietary management of folate is necessary for adolescents and young adults who have undergone kidney transplantation during childhood.

Cystatin C-based equation for estimating glomerular filtration rate in Japanese children and adolescents.

BACKGROUND: Renal inulin clearance is the gold standard for evaluation of kidney function, but is compromised by problems of collecting urine samples in children, especially those <6 years or with a bladder dysfunction. Therefore, we should utilize the serum cystatin C (cysC)-based estimated glomerular filtration rate (eGFR) for measuring serum cysC. The purpose of the present study is to determine the applicability of the new serum cysC-based eGFR in Japanese children and adolescents, including infants with chronic kidney disease (CKD), for evaluation of renal function. METHODS: Inulin clearance and standardized serum cysC level determined by the colloidal gold immunoassay were measured in 135 pediatric CKD patients between the ages of 1 month and 18 years with no underlying disease that affects renal function except CKD, to determine serum cysC-based eGFR in Japanese children and adolescents. RESULTS: We showed the inulin clearance by expression of 1/serum cysC in pediatric CKD patients, which resulted in the equation: inulin GFR (mL/min/1.73 m(2)) = 104.1 × 1/serum cysC (mg/L) - 7.80. We also validated the cysC-based eGFR formula for Japanese adults. eGFR values obtained with the adult formula significantly underestimated GFR by approximately 8 % in children with CKD. CONCLUSION: We determined the new cysC-based eGFR formula is useful for clinical screening of renal function in Japanese children and adolescents, including infants.

Creatinine-based equation to estimate the glomerular filtration rate in Japanese children and adolescents with chronic kidney disease.

BACKGROUND: Renal inulin clearance is the gold standard for evaluation of kidney function, but cannot be measured easily in children. Therefore, we utilize the serum creatinine (Cr)-based estimated GFR (eGFR) measuring serum Cr by the enzymatic method, and we have reported simple serum Cr-based eGFR in Japanese children aged between 2 and 11 years old. Furthermore, we should use serum Cr-based eGFR in Japanese adolescents as well as children with chronic kidney disease for evaluation of renal function. METHODS: The inulin clearance and serum Cr level determined by an enzymatic method were measured in 131 pediatric chronic kidney disease (CKD) patients between the ages of 2 and 18 years old with no underlying disease affecting renal function except CKD to determine the serum Cr-based eGFR in Japanese children and adolescents. RESULTS: We offer the complex estimated GFR equation using polynomial formulae for reference serum creatinine levels with body length in Japanese children except infants, resulting in the following equation:[Formula: see text] Reference serum Cr levels (y) are shown by the following two equations of body length (x):[Formula: see text] CONCLUSION: The new polynomial eGFR formula showing the relationship with body length and serum Cr level may be applicable for clinical screening of renal function in Japanese children and adolescents aged between 2 and 18 years.

Overestimation of the risk of progression to end-stage renal disease in the poor prognosis' group according to the 2002 Japanese histological classification for immunoglobulin A nephropathy.

BACKGROUND: The current (2012) histological classification of immunoglobulin A nephropathy was established using a case-control study of 287 patients. However, the risk of progression to end-stage renal disease (ESRD) has not been validated for the previous (2002) classification. This study aimed to determine whether the previous classification could identify the risk of long-term renal outcome through re-analysis of the 2012 cohort. METHODS: On the basis of the 2002 classification, namely 'good prognosis', 'relatively good prognosis', 'relatively poor prognosis', and 'poor prognosis', we examined the clinical data at the time of biopsy, the correlation between the 2002 classification and long-term renal outcomes, and a patient-by-patient correlation between the 2002 and 2012 classification systems. This was performed by analyzing samples from the 287 patients used to establish the 2012 classification. RESULTS: The rate of decline of estimated glomerular filtration rate was greater and the odds ratio of progression to ESRD was higher in the 'poor prognosis' group. In contrast, the odds ratio for renal death was comparable between the groups described as 'relatively poor prognosis' and 'relatively good prognosis' in the 2002 classification. Many patients in the 2002 classification were classified with a lower histological grade in the current classification, but none were classified with a higher grade. CONCLUSIONS: The 2002 classification could also identify the risk of progression to ESRD. However, it was overestimated for patients in the 'poor prognosis' group in the 2002 classification, as that group included patients with milder histological damage.