Low C3 in a 4-month-old baby: is it a problem?

A 4-month-old male baby was admitted because his father and uncles had chronic kidney disease. His father was diagnosed with membranoproliferative glomerulonephritis at the age of 5, underwent a kidney transplant at the age of 22, and lost the graft due to recurrence of the disease. In contrast, the young uncle was diagnosed with C3 glomerulopathy and mycophenolate mofetil and eculizumab were initiated early. It was remarkable that our patient had normal kidney function and urine analyses but low serum C3 level (0.56 g/L; N, 0.9-1.8 g/L). In the disease-associated clinical exome analysis, a heterozygous change in the CFH gene was found. The same mutation was found homozygous in the uncle. In genetically inherited diseases, findings may occur sequentially; early screening of at-risk individuals contributes to kidney survival.

Therapeutic apheresis: is it safe in children with kidney disease?

BACKGROUND: Therapeutic apheresis (TA) is already used to treat various diseases in the field of nephrology. The aim of this study was to evaluate the frequency and types of complications that occur during TA in children with kidney disease. METHODS: Records of children (≤ 18 years) who underwent TA between 2007 and 2022 were retrospectively reviewed. Children with missing data and those with a diagnosis of nonnephrological disease were excluded. RESULTS: A total of 1214 TA sessions, including 1147 therapeutic plasma exchange (TPE) sessions and 67 immunoadsorption (IA) sessions, were performed on the 108 patients enrolled in the study. Forty-seven percent of the patients were male, and the mean age was 12.22 ± 4.47 years. Posttransplant antibody-mediated rejection (64.8%) and hemolytic uremic syndrome (14.8%) were the most common diagnoses indicating TA. Overall, 17 different complications occurred in 58 sessions (4.8%), and 53 sessions (4.6%) were not completed because of these complications. The distribution of complications among the patients was as follows: 41.4% had technical complications, 25.9% had allergic complications, and 32.7% had others. The most common technical complication was insufficient flow (37.5%). The incidence of complications was greater in patients aged 3-6 years than in patients in the other age groups (p = 0.031). The primary disease, type of vascular access, and rate of fresh frozen plasma/albumin use were similar between patients with and without complications (p values of 0.359 and 0.125 and 0.118, respectively). CONCLUSIONS: Our study showed that complications occurred in only 4.8% of TA sessions. The most common complication was technical problems.

Complement gene mutations in children with C3 glomerulopathy: do they affect the response to mycophenolate mofetil?

BACKGROUND: C3 glomerulopathy (C3G) is a complement-mediated disease. Although genetic studies are not required for diagnosis, they are valuable for treatment planning and prognosis prediction. The aim of this study is to investigate the clinical phenotypes, kidney survival, and response to mycophenolate mofetil (MMF) treatment in pediatric C3G patients with and without mutations in complement-related genes. METHODS: Sixty pediatric C3G patients were included, divided into two groups based on complement-related gene mutations. Demographic and clinical-pathological findings, treatment modalities, and outcome data were compared, and Kaplan-Meier analysis was performed for kidney survival. RESULTS: Out of the 60 patients, 17 had mutations. The most common mutation was in the CFH gene (47%). The mean age at diagnosis was higher in the group with mutation (12.9 ± 3.6 vs. 11.2 ± 4.1 years, p = 0.039). While the patients without mutation most frequently presented with nephritic syndrome (44.2%), the mutation group was most likely to have asymptomatic urinary abnormalities (47.1%, p = 0.043). Serum parameters and histopathological characteristics were similar, but hypoalbuminemia was more common in patients without mutation. During 45-month follow-up,10 patients progressed to chronic kidney disease stage 5 (CKD5), with 4 having genetic mutation. The time to develop CKD5 was longer in the mutation group but not significant. MMF treatment had no effect on progression in either group. CONCLUSIONS: This study is the largest pediatric C3G study examining the relationship between genotype and phenotype. We showed that the mutation group often presented with asymptomatic urinary abnormalities, was diagnosed relatively late but was not different from the without mutation group in terms of MMF treatment response and kidney survival.

Urine soluble TLR4 levels may contribute to predict urinary tract infection in children: the UTILISE Study.

BACKGROUND: One of the most common bacterial infections in childhood is urinary tract infection (UTI). Toll-like receptors (TLRs) contribute to immune response against UTI recognizing specific pathogenic agents. Our aim was to determine whether soluble TLR4 (sTLR4), soluble TLR5 (sTLR5) and interleukin 8 (IL-8) can be used as biomarkers to diagnose UTI. We also aimed to reveal the relationship between urine Heat Shock Protein 70 (uHSP70) and those biomarkers investigated in this study. METHODS: A total of 802 children from 37 centers participated in the study. The participants (n = 282) who did not meet the inclusion criteria were excluded from the study. The remaining 520 children, including 191 patients with UTI, 178 patients with non-UTI infections, 50 children with contaminated urine samples, 26 participants with asymptomatic bacteriuria and 75 healthy controls were included in the study. Urine and serum levels of sTLR4, sTLR5 and IL-8 were measured at presentation in all patients and after antibiotic treatment in patients with UTI. RESULTS: Urine sTLR4 was higher in the UTI group than in the other groups. UTI may be predicted using 1.28 ng/mL as cut-off for urine sTLR4 with 68% sensitivity and 65% specificity (AUC = 0.682). In the UTI group, urine sTLR4 levels were significantly higher in pyelonephritis than in cystitis (p < 0.0001). Post-treatment urine sTLR4 levels in the UTI group were significantly lower than pre-treatment values (p < 0.0001). CONCLUSIONS: Urine sTLR4 may be used as a useful biomarker in predicting UTI and subsequent pyelonephritis in children with UTI. A higher resolution version of the Graphical abstract is available as Supplementary information.

Characteristics and predictors of chronic kidney disease in children with myelomeningocele: a nationwide cohort study.

BACKGROUND: Myelomeningocele (MMC) is highly prevalent in developing countries, and MMC-related neurogenic bladder is an important cause of childhood chronic kidney disease (CKD). This nationwide study aimed to evaluate demographic and clinical features of pediatric patients with MMC in Turkey and risk factors associated with CKD stage 5. METHODS: Data from children aged 0-19 years old, living with MMC in 2022, were retrospectively collected from 27 pediatric nephrology centers. Patients > 1 year of age without pre-existing kidney abnormalities were divided into five groups according to eGFR; CKD stages 1-5. Patients on dialysis, kidney transplant recipients, and those with eGFR < 15 ml/min/1.73 m2 but not on kidney replacement therapy at time of study constituted the CKD stage 5 group. RESULTS: A total of 911 (57.8% female) patients were enrolled, most of whom were expectantly managed. Stages 1-4 CKD were found in 34.3%, 4.2%, 4.1%, and 2.4%, respectively. CKD stage 5 was observed in 5.3% of patients at median 13 years old (range 2-18 years). Current age, age at first abnormal DMSA scan, moderate-to-severe trabeculated bladder on US and/or VCUG, and VUR history were independent risk factors for development of CKD stage 5 (OR 0.752; 95%; CI 0.658-0.859; p < 0.001; OR 1.187; 95% CI 1.031-1.367; p = 0.017; OR 10.031; 95% CI 2.210-45.544; p = 0.003; OR 2.722; 95% CI 1.215-6.102; p = 0.015, respectively). Only eight CKD stage 5 patients underwent surgery related to a hostile bladder between 1 and 15 years old. CONCLUSION: MMC-related CKD is common in childhood in Turkey. A proactive approach to neurogenic bladder management and early protective surgery in selected cases where conservative treatment has failed should be implemented to prevent progressive kidney failure in the pediatric MMC population in our country.

Adolescence-onset atypical hemolytic uremic syndrome: is it different from infant-onset?

BACKGROUND: Atypical hemolytic uremic syndrome (aHUS) is a rare, mostly complement-mediated thrombotic microangiopathy. The majority of patients are infants. In contrast to infantile-onset aHUS, the clinical and genetic characteristics of adolescence-onset aHUS have not been sufficiently addressed to date. METHODS: A total of 28 patients (21 girls, 7 boys) who were diagnosed as aHUS between the ages of ≥10 years and <18 years were included in this study. All available data in the Turkish Pediatric aHUS registry were collected and analyzed. RESULTS: The mean age at diagnosis was 12.8±2.3 years. Extra-renal involvement was noted in 13 patients (46.4%); neurological involvement was the most common (32%). A total of 21 patients (75%) required kidney replacement therapy. Five patients (17.8%) received only plasma therapy and 23 (82%) of the patients received eculizumab. Hematologic remission and renal remission were achieved in 25 (89.3%) and 17 (60.7%) of the patients, respectively. Compared with the infantile-onset aHUS patients, adolescent patients had a lower complete remission rate during the first episode (p = 0.002). Genetic analyses were performed in all and a genetic variant was detected in 39.3% of the patients. The mean follow-up duration was 4.9±2.6 years. At the last visit, adolescent patients had lower eGFR levels (p = 0.03) and higher rates of chronic kidney disease stage 5 when compared to infantile-onset aHUS patients (p = 0.04). CONCLUSIONS: Adolescence-onset aHUS is a rare disease but tends to cause more permanent renal dysfunction than infantile-onset aHUS. These results may modify the management approaches in these patients.

Comprehensive evaluation of patients with primary hyperoxaluria type 1: A nationwide study.

BACKGROUND: Primary hyperoxaluria type 1 (PH1) is characterized by increased endogenous oxalate production and deposition as calcium oxalate crystals. The main manifestations are nephrocalcinosis/nephrolithiasis, causing impaired kidney function. We aimed to evaluate the clinical characteristics and overall outcomes of paediatric PH1 patients in Turkey. METHODS: This is a nationwide, multicentre, retrospective study evaluating all available paediatric PH1 patients from 15 different paediatric nephrology centres in Turkey. Detailed patient data was collected which included demographic, clinical and laboratory features. Patients were classified according to their age and characteristics at presentation: patients presenting in the first year of life with nephrocalcinosis/nephrolithiasis (infantile oxalosis, Group 1), cases with recurrent nephrolithiasis diagnosed during childhood (childhood-onset PH1, Group 2), and asymptomatic children diagnosed with family screening (Group 3). RESULTS: Forty-eight patients had a mutation consistent with PH1. The most common mutation was c.971_972delTG (25%). Infantile oxalosis patients had more advanced chronic kidney disease (CKD) or kidney failure necessitating dialysis (76.9% vs. 45.5%). These patients had much worse clinical course and mortality rates seemed to be higher (23.1% vs. 13.6%). Patients with fatal outcomes were the ones with significant comorbidities, especially with cardiovascular involvement. Patients in Group 3 were followed with better outcomes, with no kidney failure or mortality. CONCLUSION: PH1 is not an isolated kidney disease but a systemic disease. Family screening helps to preserve kidney function and prevent systemic complications. Despite all efforts made with traditional treatment methods including transplantation, our results show devastating outcomes or mortality.

Comparison of EULAR/PRINTO/PReS Ankara 2008 and 2022 ACR/EULAR Classification Criteria for Granulomatosis with Polyangiitis in Children.

OBJECTIVE: Granulomatosis with polyangiitis (GPA) is an antineutrophil cytoplasmic antibody-associated vasculitis. The 2022 American College of Rheumatology/European Alliance of Associations for Rheumatology (ACR/EULAR)-endorsed classification criteria for GPA was derived using data only from adult patients. We aimed to assess the performance of the ACR/EULAR classification criteria for GPA in pediatric patients and compare it with the EULAR/Pediatric Rheumatology International Trials Organization (PRINTO)/Pediatric Rheumatology European Society (PReS)-endorsed Ankara 2008 criteria for GPA. METHODS: Retrospective data of pediatric patients with GPA in 20 centers from 9 countries were evaluated. The diagnosis of GPA was made according to the expert opinion. The sensitivity, specificity, positive predictive value, and negative predictive value of the criteria sets were evaluated. RESULTS: The study included 77 patients with GPA and 108 controls (immunoglobulin A vasculitis (n = 44), Takayasu's arteritis (n = 20), microscopic polyangiitis (n = 16), polyarteritis nodosa (n = 14), Behçet's disease (n = 12), eosinophilic granulomatosis with polyangiitis (n = 1), and Cogan's syndrome (n = 1)) with a median age of 17.8 and 15.2 years, respectively. Of patients with GPA, constitutional symptoms (85.7%) and ear-nose-throat involvement (79.2%) were the most common presentations. In the GPA group, 73 patients fulfilled the Ankara 2008 criteria and 69 the ACR/EULAR classification criteria. Sensitivities of the Ankara 2008 criteria and the ACR/EULAR classification criteria were 94.8% and 89.6%, while specificities were 95.3% and 96.3%, respectively. No significant difference was found between sensitivities and specificities of both classification criteria (p= 0.229 and p= 0.733, respectively). CONCLUSION: In children, both the ACR/EULAR and EULAR/PRINTO/PReS Ankara 2008 classification criteria for GPA perform well and similarly.

Urinary HSP70 improves diagnostic accuracy for urinary tract infection in children: UTILISE study.

BACKGROUND: The accuracy of conventional urinalysis in diagnosing urinary tract infection (UTI) in children is limited, leading to unnecessary antibiotic exposure in a large fraction of patients. Urinary heat shock protein 70 (uHSP70) is a novel marker of acute urinary tract inflammation. We explored the added value of uHSP70 in discriminating UTI from other infections and conditions confused with UTI. METHODS: A total of 802 children from 37 pediatric centers in seven countries participated in the study. Patients diagnosed with UTI (n = 191), non-UTI infections (n = 178), contaminated urine samples (n = 50), asymptomatic bacteriuria (n = 26), and healthy controls (n = 75) were enrolled. Urine and serum levels of HSP70 were measured at presentation in all patients and after resolution of the infection in patients with confirmed UTI. RESULTS: Urinary (u)HSP70 was selectively elevated in children with UTI as compared to all other conditions (p < 0.0001). uHSP70 predicted UTI with 89% sensitivity and 82% specificity (AUC = 0.934). Among the 265 patients with suspected UTI, the uHSP70 > 48 ng/mL criterion identified the 172 children with subsequently confirmed UTI with 90% sensitivity and 82% specificity (AUC = 0.862), exceeding the individual diagnostic accuracy of leukocyturia, nitrite, and leukocyte esterase positivity. uHSP70 had completely normalized by the end of antibiotic therapy in the UTI patients. Serum HSP70 was not predictive. CONCLUSIONS: Urine HSP70 is a novel non-invasive marker of UTI that improves the diagnostic accuracy of conventional urinalysis. We estimate that rapid urine HSP70 screening could spare empiric antibiotic administration in up to 80% of children with suspected UTI. A higher resolution version of the Graphical abstract is available as Supplementary information.

Kidney disease profile and encountered problems during follow-up in Syrian refugee children: a multicenter retrospective study.

BACKGROUND: Children are one of the most vulnerable groups in conflict zones, especially those with chronic diseases. This study aimed to investigate kidney disease profiles and problems during follow-up in a population of Syrian refugee children residing in Turkey. METHODS: Syrian refugee children aged between 0 and 18 years were included in the study. Demographic data, diagnosis, particular interventions due to nephrological problems, and problems encountered during follow-up were obtained from all participating pediatric nephrology centers. RESULTS: Data from 633 children from 22 pediatric nephrology centers were included. Mean age of the children was 94.8 ± 61.7 months and 375 were male (59%). 57.7% had parental consanguinity and 23.3% had a close relative(s) with kidney disease. The most common kidney diseases were congenital anomalies of the kidney and urinary tract (CAKUT) (31.0%), glomerular disease (19.9%), chronic kidney disease (CKD) (14.8%), and urolithiasis (10.7%). Frequent reasons for CAKUT were nonobstructive hydronephrosis (23.0%), vesico-ureteral reflux (18.4%), and neurogenic bladder (15.8%). The most common etiology of glomerular diseases was nephrotic syndrome (69%). Ninety-four children had CKD, and 58 children were on chronic dialysis. Six children had kidney transplantation. Surgical intervention was performed on 111 patients. The language barrier, lack of medical records, and frequent disruptions in periodic follow-ups were the main problems noted. CONCLUSIONS: CAKUT, glomerular disease, and CKD were highly prevalent in Syrian refugee children. Knowing the frequency of chronic diseases and the problems encountered in refugees would facilitate better treatment options and preventive measures.

A rare complication of Behçet's disease in a 12-year-old girl: a large intracardiac thrombosis.

Behcet's disease is a multi-systemic inflammatory disease with a clinical spectrum as a triple complex of recurrent oral, genital ulcers, and uveitis. Cardiac involvement in patients with Behcet's disease is extremely rare and often associated with poor prognosis. Behcet's disease should be considered in the differential diagnosis of right ventricular mass especially in young adults, even there is no typical clinical features of Behcet's disease. In this case, a 12-year-old girl who admitted with chest pain and haemoptysis and then was diagnosed with intracardiac thrombus related to Behcet's disease during follow-up was described.

Thrombotic Microangiopathy Associated with Macrophage Activation Syndrome: A Multinational Study of 23 Patients.

OBJECTIVE: To describe the clinical characteristics, treatment, and outcomes of a multinational cohort of patients with macrophage activation syndrome (MAS) and thrombotic microangiopathy (TMA). STUDY DESIGN: International pediatric rheumatologists were asked to collect retrospectively the data of patients with the co-occurrence of MAS and TMA. Clinical and laboratory features of patients with systemic juvenile idiopathic arthritis (sJIA)-associated MAS and TMA were compared with those of an historical cohort of patients with sJIA and MAS. RESULTS: Twenty-three patients with MAS and TMA were enrolled: 17 had sJIA, 2 systemic lupus erythematosus, 1 juvenile dermatomyositis, 1 mixed connective tissue disease, and 2 undifferentiated connective tissue disease. Compared with the historical cohort of MAS, patients with sJIA with coexistent MAS and TMA had higher frequencies of renal failure and neurologic involvement, hemorrhage, jaundice, and respiratory symptoms, as well as more severe anemia and thrombocytopenia, higher levels of alanine aminotransferase, lactate dehydrogenase, bilirubin and D-dimer, and lower levels of albumin and fibrinogen. They also required admission to the intensive care unit more frequently. Among patients tested, complement abnormalities and reduced ADAMTS13 activity were observed in 64.3% and 44.4% of cases, respectively. All patients received glucocorticoids. Treatment for TMA included plasma-exchange, eculizumab, and rituximab. CONCLUSIONS: The possible coexistence of MAS and TMA in rheumatic diseases may be underrecognized. This association should be considered in patients with MAS who develop disproportionate anemia, thrombocytopenia, and lactate dehydrogenase increase, or have multiorgan failure.

Transplantation in pediatric aHUS within the era of eculizumab therapy.

aHUS is caused by the over-activation and dysregulation of the alternative complement pathway. Data regarding outcomes of pediatric aHUS patients after kidney transplantation are still very scarce. Accordingly, the aim of this study was to describe the clinical findings and outcomes of pediatric aHUS patients after renal transplantation. This is a retrospective, multicenter study including 12 patients from the national registry system. Among the 12 patients, eight had received prophylactic eculizumab and none of those patients (except one) had experienced aHUS recurrence during a median follow-up period of 58.5 (min-max, 4-94) months. Although eculizumab had been started on the day before transplantation in one of them, aHUS recurrence occurred during the transplantation procedure. Eculizumab had been stopped in only one patient who had no complement gene mutation after 35 months of therapy, and recurrence had not been observed during the 19 months of follow-up. In three patients, maintenance doses had been spaced out without any recurrence. One additional patient with anti-CFH antibody received only two doses of eculizumab for transplantation and had been followed for 46 months without aHUS recurrence. The remaining three patients had not received anti-C5 therapy and none of those patients experienced aHUS recurrence during a median follow-up period of 21 (min-max, 9-42) months. Prophylactic eculizumab is a safe and effective treatment for the prevention of aHUS recurrence. Eculizumab interval prolongation, discontinuation, and transplantation without eculizumab prophylaxis can be tried in selected patients with close follow-up.

Evaluation of non-infectious complications of peritoneal dialysis in children: a multicenter study.

BACKGROUND: Peritoneal dialysis (PD) is the most common kidney replacement therapy in children. Complications associated with PD affect treatment success and sustainability. The aim of this study was to investigate the frequency of PD-related non-infectious complications and the predisposing factors. METHODS: Retrospective data from 11 centers in Turkey between 1998 and 2018 was collected. Non-infectious complications of peritoneal dialysis (NICPD), except metabolic ones, in pediatric patients with regular follow-up of at least 3 months were evaluated. RESULTS: A total of 275 patients were included. The median age at onset of PD and median duration of PD were 9.1 (IQR, 2.5-13.2) and 7.6 (IQR, 2.8-11.9) years, respectively. A total of 159 (57.8%) patients encountered 302 NICPD within the observation period of 862 patient-years. The most common NIPCD was catheter dysfunction (n = 71, 23.5%). At least one catheter revision was performed in 77 patients (28.0%). Longer PD duration and presence of swan neck tunnel were associated with the development of NICPD (OR 1.191; 95% CI 1.079-1.315, p = 0.001 and OR 1.580; 95% CI 0.660-0.883, p = 0.048, respectively). Peritoneal dialysis was discontinued in 145 patients; 46 of whom (16.7%) switched to hemodialysis. The frequency of patients who were transferred to hemodialysis due to NICPD was 15.2%. CONCLUSIONS: Peritoneal dialysis-related non-infectious complications may lead to discontinuation of therapy. Presence of swan neck tunnel and long duration of PD increased the rate of NICPD. Careful monitoring of patients is necessary to ensure that PD treatment can be maintained safely.

Predictors of poor kidney outcome in children with C3 glomerulopathy.

BACKGROUND: C3 glomerulopathy (C3G) is characterized by heterogeneous clinical presentation, outcome, and predominant C3 accumulation in glomeruli without significant IgG. There is scarce outcome data regarding childhood C3G. We describe clinical and pathological features, treatment and outcomes, and risk factors for progression to chronic kidney disease stage 5 (CKD5) in the largest pediatric series with biopsy-proven C3G. METHODS: Sixty pediatric patients with C3G from 21 referral centers in Turkey were included in this retrospective study. Patients were categorized according to CKD stage at last visit as CKD5 or non-CKD5. Demographic data, clinicopathologic findings, treatment, and outcome data were compared and possible risk factors for CKD5 progression determined using Cox proportional hazards model. RESULTS: Mean age at diagnosis was 10.6 ± 3.0 years and follow-up time 48.3 ± 36.3 months. Almost half the patients had gross hematuria and hypertension at diagnosis. Nephritic-nephrotic syndrome was the commonest presenting feature (41.6%) and 1/5 of patients presented with nephrotic syndrome. Membranoproliferative glomerulonephritis was the leading injury pattern, while 40 patients had only C3 staining. Patients with DDD had significantly lower baseline serum albumin compared with C3GN. Eighteen patients received eculizumab. Clinical remission was achieved in 68.3%. At last follow-up, 10 patients (16.6%) developed CKD5: they had lower baseline eGFR and albumin and higher frequency of nephrotic syndrome and dialysis requirement than non-CKD5 patients. Lower serum albumin and eGFR at diagnosis were independent predictors for CKD5 development. CONCLUSIONS: Children with C3G who have impaired kidney function and hypoalbuminemia at diagnosis should be carefully monitored for risk of progression to CKD5. Graphical abstract.

A nationwide retrospective study in Turkish children with nephrocalcinosis.

BACKGROUND: Nephrocalcinosis (NC) is defined as calcium deposition in the kidney parenchyma and tubules. This study aims to determine the etiology, risk factors, and follow-up results of patients with NC in Turkey. METHODS: Patients diagnosed with NC in the pediatric nephrology Department Units of 19 centers from all geographical regions of Turkey over a 10-year period (2010-2019) were included in the study. The medical records from the centers were reviewed and demographic data, admission complaints, medical history, systemic and genetic disorders, risk factors for NC, treatment details, and presence of NC after one-year follow-up, were recorded retrospectively. RESULTS: The study sample included 195 patients (88 females, 107 males). The mean age at diagnosis was 39.44 ± 47.25 (0.5-208) months; 82/190 patients (43.2%) were diagnosed incidentally; 46/195 patients (23.6%) had an underlying disease; idiopathic hypercalciuria was detected in 75/195 (38.4%) patients. The most common systemic diseases were distal renal tubular acidosis in 11/46 patients (23.9%), primary hyperoxaluria in 9/46 patients (19.6%) and Bartter syndrome in 7/46 patients (15.3%). After one year of follow-up, NC resolved in 56/159 patients (35.2%) and they all did not have an underlying systemic disease. DISCUSSION: The most common presentation of NC was incidental. Distal renal tubular acidosis and primary hyperoxaluria were the main systemic diseases leading to NC, while hypercalciuria was the most common metabolic risk factor. Nephrocalcinosis was found to remain in most of the patients at a one-year follow-up. It may resolve particularly in patients with no underlying systemic disease.

Orthostatic proteinuria: an overestimated phenomenon?

BACKGROUND: Although orthostatic proteinuria (OP) is the most common cause of childhood proteinuria, excluding transient proteinuria, data regarding prevalence and long-term prognosis are limited. We aimed to determine prevalence of OP in healthy schoolchildren evaluating relationships with age, gender and body mass index, and determine follow-up. METHODS: A total of 1701 healthy children aged 6-15 years were selected using a population-based, stratified, cluster-sampling method; and random urine samples were taken. For proteinuria ≥ 1+ in first urine samples, second and third random samples were taken at least 2 weeks apart to exclude transient proteinuria. For continuing proteinuria after third samples, first morning urine samples were collected. Cases where proteinuria was not detected in first morning urine samples were diagnosed as OP. RESULTS: Sixty-four of 1701 children (3.7%) had proteinuria on first random urine samples. After second and third urine samples, proteinuria persisted in only 16 (0.94%). OP was detected in 11 (0.65%). Prevalence of OP tended to decrease with increasing BMI, though not statistically significant. All 7 cases with OP who were re-evaluated later, had no proteinuria 3 years after diagnosis. CONCLUSIONS: Prevalence of OP in our study was lower than the literature. At least three random urine samples should be taken to exclude transient proteinuria in an asymptomatic child/adolescent before making a diagnosis of OP using first morning urine samples. OP is a benign condition and resolves spontaneously in most cases. Underweight children had a tendency for OP compared with overweight and obese children; however, further studies with larger number of patients are needed.

Clinical and histopathological prognostic factors affecting the renal outcomes in childhood ANCA-associated vasculitis.

OBJECTIVE: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) are very rare in childhood with an increased risk of morbidity and mortality. We aimed to evaluate renal prognostic factors in childhood AAV from the perspective of ANCA serotype, histopathological classification, and five-factor score (FFS). METHODS: Pediatric AAV patients from 11 referral centers in Turkey had been included to the study. The demographics, clinical findings, AAV subtypes, outcomes, and FFS were evaluated retrospectively. Kidney biopsies were classified histopathologically. RESULTS: Totally, 39 patients were enrolled in the study. Among all patients, 74.4% had renal involvement, 56.4% ear-throat-nose involvement, and 51.3% had musculoskeletal involvement. Proteinase 3 (PR3)-ANCA was positive in 48.7%, and myeloperoxidase (MPO)-ANCA was positive in 30.8%. 69.2% of patients had impaired renal function, and 28.2% had progressed to end-stage renal disease (ESRD) during the follow-up. At the time of diagnosis, FFS was ≥ 2 in 53.8%. The most common histopathologic classifications were as follows: crescentic type in 40.7% and sclerotic type in 25.9%. Gastrointestinal and renal involvement, MPO-ANCA positivity, serum creatinine levels, and impaired renal function during the follow-up were significantly higher in patients with FFS ≥ 2, compared to patients with FFS < 2. Patients with FFS ≥ 2 had more common crescentic, mixed and sclerotic histopathologic findings in biopsies. By logistic regression analysis forward method, the strongest single-risk factor among all the parameters was the initial level of creatinine in patients with ESRD, compared to the other patients (p = 0,007). CONCLUSIONS: Evaluation of the FFS, ANCA serology, and the creatinine levels may help to predict renal prognosis.