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.

Etiologic-sociodemographic assessment and comparison of dialysis modalities in pediatric Syrian migrants with chronic kidney disease.

BACKGROUND: Chronic kidney disease (CKD) and end-stage renal disease (ESRD) are among the important causes of mortality and morbidity in childhood. Early diagnosis and treatment of the underlying primary disease may prevent most of CKD patients from progressing to ESRD. There is no study examining chronic kidney diseases and dialysis modalities in Syrian immigrant children. We aimed to retrospectively research the etiologic, sociodemographic, and clinical factors in CKD among Syrian refugee children, and at the same time, to compare the clinical characteristics of patients with ESRD on peritoneal dialysis and hemodialysis. METHODS: Our study included a total of 79 pediatric Syrian patients aged from 2-16 years monitored at Hatay State Hospital pediatric nephrology clinic with diagnosis of various stages of CKD and with ESRD. Physical-demographic features and clinical-laboratory information were retrospectively screened. RESULTS: The most common cause of CKD was congenital anomalies of the kidneys and urinary tracts (CAKUT) (37.9%). Other causes were urolitiasis (15.1%), nephrotic syndrome (10.1%), spina bifida (8.8%), hemolytic uremic syndrome (7.5%), and glomerulonephritis (7.5%). Twenty-five patients used hemodialysis due to bad living conditions. Only 2 of the patients with peritoneal dialysis were using automatic peritoneal dialysis (APD), with 5 using continuous ambulatory peritoneal dialysis (CAPD). Long-term complications like left ventricle hypertrophy and retinopathy were significantly higher among hemodialysis patients. There was no difference identified between the groups in terms of hypertension and sex. CONCLUSION: Progression to ESRD due to preventable reasons is very frequent among CKD patients. For more effective use of peritoneal dialysis in pediatric patients, the responsibility of states must be improved.

COVID-19 in pediatric nephrology centers in Turkey.

BACKGROUND: There is limited data on COVID-19 disease in children with kidney disease. We aimed to investigate the characteristics and prognosis of COVID-19 in pediatric nephrology patients in Turkey. METHODS: This was a national, multicenter, retrospective cohort study based on an online survey evaluating the data between 11th March 2020 and 11th March 2021 as an initial step of a detailed pediatric nephrology COVID-19 registry. RESULTS: Two hundred and three patients (89 girls and 114 boys) were diagnosed with COVID-19. One-third of these patients (36.9%) were between 10-15 years old. Half of the patients were on kidney replacement therapy: kidney transplant (KTx) recipients (n = 56, 27.5%), patients receiving chronic hemodialysis (n = 33, 16.3%) and those on peritoneal dialysis (PD) (n = 18, 8.9%). Fifty-four (26.6%) children were asymptomatic. Eighty-two (40.3%) patients were hospitalized and 23 (28%) needed intensive care unit admission. Fifty-five percent of the patients were not treated, while the remaining was given favipiravir (20.7%), steroid (16.3%), and hydroxychloroquine (11.3%). Acute kidney injury developed in 19.5% of hospitalized patients. Five (2.4%) had MIS-C. Eighty-three percent of the patients were discharged without any apparent sequelae, while 7 (3.4%) died. One hundred and eight health care staff were infected during the study period. DISCUSSION: COVID-19 was most commonly seen in patients who underwent KTx and received HD. The combined immunosuppressive therapy and frequent exposure to the hospital setting may increase these patients' susceptibility. Staff infections before vaccination era were alarming, various precautions should be taken for infection control, particularly optimal vaccination coverage.

Respiratory function in children with nephrotic syndrome: Comparative evaluation of impulse oscillometry and spirometry.

AIM: To evaluate the respiratory functions of children with nephrotic syndrome (NS) by impulse oscillometry (IOS) and its correlation with spirometry. METHODS: Fifty-five NS patients aged 3-18 years were included as the study group and 40 healthy children of the same age formed the control group. Patients were divided into nephrotic phase (first attack and relapse) and remission. Demographic, anthropometric, and laboratory data of the children were recorded. Respiratory functions were evaluated by IOS and spirometry. Children over 6-years old performed both IOS and spirometry while children under 6 years performed only IOS. RESULTS: The R (R5%, R10%, R5-20), AX and Z5% values of IOS in patients with nephrotic phase were higher than remission patients and control group while spirometry indices of PEF% and MEF25-75% were lower. Z scores of MEF25-75 were significantly negatively correlated with z scores of R5, R10, Z5, and Fres while they were significantly positively correlated with z scores of X values (5, 10, 15, and 20 Hz). Z scores of forced expiratory volume in 1 /forced vital capacity significantly negatively correlated with z scores of R values (R5, R10), Z5 and AX and positively correlated with z scores of X values (X5, X10, X15 Hz). CONCLUSION: Our study demonstrated that respiratory functions measured by IOS and spirometry were affected at the time of nephrotic phase in NS patients. IOS, a novel method easily applicable even in small children, is a potentially valuable tool to detect this condition; given its good correlation with spirometry.

Rituximab treatment for difficult-to-treat nephrotic syndrome in children: a multicenter, retrospective study

Background/aim: This study aimed to evaluate the efficacy of rituximab in children with difficult-to-treat nephrotic syndrome, considering the type of disease (steroid-sensitive or ­resistant) and the dosing regimen. Materials and methods: This multicenter retrospective study enrolled children with difficult-to-treat nephrotic syndrome on rituximab treatment from 13 centers. The patients were classified based on low (single dose of 375 mg/m2) or high (2-4 doses of 375 mg/m2) initial dose of rituximab and the steroid response. Clinical outcomes were compared. Results: Data from 42 children [20 steroid-sensitive (frequent relapsing / steroid-dependent) and 22 steroid-resistant nephrotic syndrome, aged 1.9­17.3 years] were analyzed. Eleven patients with steroid-sensitive nephrotic syndrome (55%) had a relapse following initial rituximab therapy, with the mean time to first relapse of 8.4 ± 5.2 months. Complete remission was achieved in 41% and 36% of steroid-resistant patients, with the median remission time of 3.65 months. At Year 2, eight patients in steroid-sensitive group (40%) and four in steroid-resistant group (18%) were drug-free. Total cumulative doses of rituximab were higher in steroid-resistant group (p = 001). Relapse rates and time to first relapse in steroid-sensitive group or remission rates in steroid-resistant group did not differ between the low and high initial dose groups. Conclusion: The current study reveals that rituximab therapy may provide a lower relapse rate and prolonged relapse-free survival in the steroid-sensitive group, increased remission rates in the steroid-resistant group, and a significant number of drug-free patients in both groups. The optimal regimen for initial treatment and maintenance needs to be determined.

Non-dipping phenomenon effects in monosymptomatic nocturnal enuresis treatment?

BACKGROUND: Monosymptomatic enuresis nocturna patients are shown to have disrupted blood-pressure regulation accompanying polyuria. In our study, we aimed to research the desmopressin response of enuresis patients with blood-pressure regulation problems. METHODS: The study included 175 patients, aged from 6-15 years, with a diagnosis of monosymptomatic enuresis nocturna. Before treatment, 24 h ambulatory blood-pressure monitoring (ABPM) was used to identify 52 non-dipper patients and 73 patients with normal results. The responses to desmopressin treatment and clinical and demographic characteristics affecting response were compared. RESULTS: The response to desmopressin treatment was found to be significantly low in the patients who were non-dippers on 24 h ABPM before treatment compared to those with normal ABPM results (P < 0.05). Similarly, the waking problems in the non-dipper group were found to be high by a significant degree (P < 0.05). In the non-dipper group, the systolic non-dipping rate was higher. CONCLUSIONS: Before desmopressin use, assessment of patients with a 24 h ABPM may be beneficial to select the method to be used for treatment.

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.

CFH and CFB mutations in Shiga toxin-associated haemolytic uraemic syndrome in a 6-year-old boy.

Haemolytic uraemic syndrome (HUS) is most commonly associated with Shiga toxin-producing Escherichia coli (STEC) while the recurrent hereditary atypical (aHUS) form secondary to complement system control protein mutations is relatively rare. A 6-year-old boy with complement factor H (CFH) and factor B (CFB) mutations and a history of bloody diarrhoea and PCR positivity for Shiga toxin was initially diagnosed as STEC+HUS. Acute kidney injury resolved with Eculizumab but he remains with chronic renal failure. Although the exact role of STEC in the pathogenesis of aHUS in this patient is not certain, there seems to be a relationship. However, several issues remain to be explained including the effect of genetic and environmental factors in modifying susceptibility to develop aHUS in some patients following STEC infection.Abbreviations: aHUS: atypical haemolytic uraemic syndrome; ANA: anti-nuclear antibody; ANCA: anti-neutrophil cytoplasmic antibody; ASO: anti-streptolysin O; BUN: blood urea nitrogen; CFB: complement factor B; CFH: complement factor H; EHEC: enterohaemorrhagic Escherichia coli; MCP: membrane co-factor protein; PD: peritoneal dialysis; STEC: Shiga toxin-producing Escherichia coli; STX 1-2: Shiga toxins 1-2.

Outcome of posterior urethral valve in 64 children: a single center's 22-year experience.

BACKGROUND: Posterior urethral valve (PUV) is the most serious form of congenital anomalies of kidney and urinary tract (CAKUT) in boys with significant risk of progression to chronic kidney disease (CKD). We present our long-term results in children with PUV. METHODS: Retrospective chart review of 113 children with PUV followed within the years of 1996-2018 was performed. Clinical, laboratory and epidemiologic parameters were analyzed for their impact on renal outcome. RESULTS: The median age of diagnosis was 1.00 month (1.00-132.00) and the median follow-up period was 70 months (60.00-216.00). Antenatal diagnosis was present in 33 patients (51.5%) mainly with bilateral hydronephrosis and oligohydramnios. The most common postnatal presentation was recurrent urinary tract infection (UTI) in 14 cases (21.9%) and incontinence in three cases (4.7%). Vesicoureteral-reflux (VUR) was present in 31 cases (48.4%). All patients had surgery and urinary diversion was needed in 18 (28.2%). Varying stages of chronic kidney disease (CKD) developed in 23 cases (35.9%) and rise in serum creatinine was especially prominent after the 4th year of follow-up. Of 23 CKD patients, seven (10.9%) were in ESRD and on dialysis. Mortality occurred in one (1.5%) patient. Hypertension, proteinuria and high initial serum creatinine (>1.28 mg/dL) were statistically significant risk factors for CKD, as expected. Surprisingly VUR and UTI did not show such a significant impact on CKD development. Antenatal detection was with significantly less risk for CKD. CONCLUSIONS: Our results confirm that PUV has a considerable risk for CKD development. Antenatal diagnosis, management of proteinuria and hypertension may modify this progression. But already injured kidneys still have a potential risk. The need for further research to evaluate the impact of any intervention on long term renal outcome is obvious.

Anca-associated crescentic glomerulonephritis in a child with isolated renal involvement.

Pauci-immune glomerulonephritis (GN) is more common in elderly people compared to children and the etiology is not completely understood yet. Antineutrophil cytoplasmic antibody (ANCA) positivity occurs in 80% of the patients. We report a case of a 7-year-old girl who presented with malaise and mildly elevated creatinine diagnosed as ANCA-associated pauci-immune crescentic glomerulonephritis with crescents in 20 of 25 glomeruli (80%). Of these 20 crescents, 12 were cellular, 4 fibrocellular, and 4 globally sclerotic. She did not have purpura, arthritis, or systemic symptoms and she responded well to initial immunosuppressive treatment despite relatively severe histopathology. The patient was given three pulses of intravenous methylprednisolone (30 mg/kg on alternate days) initially and continued with cyclophosphamide (CYC; 2 mg/kg per day) orally for 3 months with prednisone (1 mg/kg per day). In one month, remission was achieved with normal serum creatinine and prednisone was gradually tapered. The case of this child with a relatively rare pediatric disease emphasizes the importance of early and aggressive immunosuppressive treatment in patients with renal-limited ANCA-associated pauci-immune crescentic GN even if with a mild clinical presentation. As in our patient, clinical and laboratory findings might not always exactly reflect the severity of renal histopathology and thus kidney biopsy is mandatory in such children to guide the clinical management and predict prognosis.