Outcome of immunosuppression in children with IgA vasculitis-related nephritis.

BACKGROUND: Immunoglobulin A vasculitis with nephritis (IgAVN) is the most common vasculitis in children. Due to a lack of evidence, treatment recommendations are based on expert opinion, resulting in variation. The aim of this study was to describe the clinical presentation, treatment and outcome of an extremely large cohort of children with biopsy-proven IgAVN in order to identify prognostic risk factors and signals of treatment efficacy. METHODS: Retrospective data were collected on 1148 children with biopsy-proven IgAVN between 2005 and 2019 from 41 international paediatric nephrology centres across 25 countries and analysed using multivariate analysis. The primary outcome was estimated glomerular filtration rate (eGFR) and persistent proteinuria at last follow-up. RESULTS: The median follow-up was 3.7 years (interquartile range 2-6.2). At last follow-up, 29% of patients had an eGFR <90 mL/min/1.73 m2, 36% had proteinuria and 3% had chronic kidney disease stage 4-5. Older age, lower eGFR at onset, hypertension and histological features of tubular atrophy and segmental sclerosis were predictors of poor outcome. There was no evidence to support any specific second-line immunosuppressive regimen being superior to others, even when further analysing subgroups of children with reduced kidney function, nephrotic syndrome or hypoalbuminemia at onset. Delayed start of immunosuppressive treatment was associated with a lower eGFR at last follow-up. CONCLUSION: In this large retrospective cohort, key features associated with disease outcome are highlighted. Importantly, there was no evidence to support that any specific immunosuppressive treatments were superior to others. Further discovery science and well-conducted clinical trials are needed to define accurate treatment and improve outcomes of IgAVN.

Acute kidney injury in children with moderate-severe COVID-19 and multisystem inflammatory syndrome in children: a referral center experience.

BACKGROUND: Data on the characteristics of acute kidney injury (AKI) in pediatric COVID-19 and MIS-C are limited. We aimed to define the frequency, associated factors and early outcome of AKI in moderate, severe or critical COVID-19 and MIS-C; and to present a tertiary referral center experience from Türkiye. METHODS: Hospitalized patients ≤ 18 years of age with confirmed COVID-19 or MIS-C at Ihsan Dogramaci Children's Hospital, Hacettepe University, between March 2020-December 2021 were enrolled. The characteristics of AKI in the COVID-19 group were investigated in moderate, severe and critically ill patients; patients with mild COVID-19 were excluded. RESULTS: The median (Q1-Q3) age in the COVID-19 (n = 66) and MIS-C (n = 111) groups was 10.7 years (3.9-15.2) and 8.7 years (4.5-12.7), respectively. The frequency of AKI was 22.7% (15/66) in COVID-19 and 15.3% (17/111) in MIS-C; all MIS-C patients with AKI and 73.3% (11/15) of COVID-19 patients with AKI had AKI at the time of admission. Multivariate analyses revealed need for vasoactive/inotropic agents [Odds ratio (OR) 19.233, p = 0.002] and presence of vomiting and/or diarrhea (OR 4.465, p = 0.036) as independent risk factors of AKI in COVID-19 patients; and need for vasoactive/inotropic agents (OR 22.542, p = 0.020), procalcitonin and ferritin levels as independent risk factors of AKI in the MIS-C group. Age was correlated with lymphocyte count (r = -0.513, p < 0.001) and troponin level (r = 0.518, p < 0.001) in MIS-C patients. Length of hospital stay was significantly longer in both groups with AKI, compared to those without AKI. Mortality was 9.1% in the COVID-19 group; and was associated with AKI (p = 0.021). There was no mortality in MIS-C patients. AKI recovery at discharge was 63.6% in COVID-19 survivors and 100% in MIS-C patients. CONCLUSIONS: Independent risk factors for AKI were need for vasoactive/inotropic agents and vomiting/diarrhea in moderate, severe or critical COVID-19 patients; and need for vasoactive/inotropic agents and severe inflammation in MIS-C patients. Our findings suggest that inflammation and cardiac dysfunction are associated with AKI in MIS-C patients; and the association with age in this group merits further studies in larger groups. Early outcome is favorable; long-term follow-up for kidney functions is needed.

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.

COVID-19 vaccination among adolescents and young adults with chronic kidney conditions: a single-center experience.

BACKGROUND: Following the pandemic of COVID-19, the main focus has been on COVID-19 vaccines and herd immunity. Although the safety of the COVID-19 vaccines has been shown in clinical trials, children with chronic diseases were not included. We investigated the side effect profile and safety of the COVID-19 vaccines in adolescents with kidney disease. METHODS: A questionnaire including demographic information, history of COVID-19, vaccination status, and vaccine-related side effects was administered to the patients with chronic kidney disease (CKD) stage 2-5, glomerular disease treated with immunosuppression, and kidney transplant recipients. RESULTS: Ninety-eight patients were vaccinated with CoronaVac-inactivated SARS-CoV-2 (n=16) or BNT162b2 messenger RNA (mRNA) COVID-19 (n=82) vaccine. The mean age was 16.90±2.36 years. The most common side effects were local pain, fatigue, and fever. No serious side effects or renal disease flare were observed. There was no significant difference in the side effects reported after the BNT162b2 mRNA-RNA as compared to the Corona Vac-inactivated SARS-CoV-2 vaccine. No significant relationship was found between the frequency of side effects according to age, glomerular filtration rate, immunosuppressive treatments, CKD stage, and the underlying disease. CONCLUSION: Although the reported data are subjective because they were obtained through a questionnaire and studies with long-term follow-up are needed, our early experience suggests that the vaccine is safe and adolescents and young adults should be encouraged to be vaccinated.

COVID-19 in Children with Chronic Kidney Disease; Does it Differ Much?

BACKGROUND: COVID-19 is known to have a mild course in children, however more data on pediatric chronic kidney disease (CKD) is needed. We aimed to assess the incidence and severity of COVID-19 in pediatric CKD patients. METHODS: A questionnaire including demographics, COVID-19 history, symptoms, and vaccination status was applied to patients with CKD. We also retrospectively reviewed the presentation and outcomes of SARS-CoV-2 infection in this patient group from March 2020 to December 2021. RESULTS: 220 patients were included, 48 were found to have experienced COVID-19. There was no significant difference regarding age, gender, underlying kidney disease, CKD stage, dialysis status, type or number of immunosuppressive medications, and glomerular filtration rate between patients with and without COVID-19. Most were infected by a household member (43.8%) and during outpatient or inpatient care (18.8%). Four (8.3%) were asymptomatic, and 43 (89.6%) had mild infection. Severe COVID-19 was observed in only one patient. Eleven (22.9%) patients with COVID-19 were previously vaccinated. Acute kidney injury was detected in 4 (8.3%); as stage 1 in all. Median follow-up after COVID-19 was 4.6 months. All patients fully recovered, and no renal disease flare or death was observed. CONCLUSIONS: Although the vaccination rate was low in our cohort, the majority of the children with COVID-19 showed a mild course. Along with the vaccination, general precautions seemed to be successful for this population.

Long-term kidney follow-up after pediatric acute kidney support therapy for children less than 15 kg.

BACKGROUND: In small children, acute dialysis (pediatric acute kidney support therapy (paKST)) is increasingly used; however, it is challenging for many reasons. We compared clinical characteristics and predictors of long-term outcomes of patients < 15 kg on peritoneal dialysis (PD), hemodialysis (HD), and continuous kidney replacement therapy (CKRT). METHODS: Patients with history of paKST (CKRT, HD, PD) weighing < 15 kg and ≥ 6 months of follow-up at Hacettepe University were included. Surviving patients were evaluated at last visit. RESULTS: 109 patients (57 females) were included. Median age at paKST was 10.1 months (IQR: 2-27 months). In total, 43 (39.4%) patients received HD, 37 (34%) PD, and 29 (26.6%) CKRT. 64 (58.7%) patients died a median 3 days (IQR: 2-9.5 days) after paKST. Percentages of patients using vasopressor agents, with sepsis, and undergoing mechanical ventilation were lower in those who survived. After mean follow-up of 2.9 ± 2.1 years, 34 patients were evaluated at mean age 4.7 ± 2.4 years. Median spot urine protein/creatinine was 0.19 (IQR: 0.13-0.37) and 12 patients (35.3%) had non-nephrotic proteinuria. Three patients had estimated glomerular filtration rate (eGFR) < 90 mL/min/1.73m2 and 2 (6%) had hyperfiltration. In total 22 patients (64.7%) had ≥ 1 kidney risk factor (elevated blood pressure/hypertension, hyperfiltration, eGFR < 90 ml/min/1.73m2, and/or proteinuria) at last visit. Among 28 patients on paKST < 32 months, 21 had ≥ 1 risk factor (75%), whereas among 6 patients who had paKST ≥ 32 months, one patient had ≥ 1 risk factor (16.7%), (p = 0.014). CONCLUSIONS: Patients on paKST who undergo mechanical ventilation and vasopressor treatment should be followed-up more closely. After surviving the acute period, patients on paKST need to be followed-up closely during the chronic stage. A higher resolution version of the Graphical abstract is available as Supplementary information.

Presentation, treatment, and outcome of renovascular hypertension below 2 years of age.

Renovascular hypertension in most cases requires endovascular treatment and/or surgery. This is technically much more difficult in small children and there is very limited published knowledge in this age group. We here present treatment and outcome of young children with renovascular hypertension at our institution. Children below 2 years of age, with renovascular hypertension between January 1998 and March 2020 were retrospectively reviewed. Demographics and treatment modalities were noted. Primary outcome was blood pressure within a week after the procedures and at last available visit. Sixty-six angiographies were performed in 34 patients. Median age at time of first angiography was 1.03 (interquartile range (IQR) 0.4-1.4) years and systolic blood pressure at presentation 130 (IQR 130-150) mm Hg. Thirty-eight percent (13/34) of children were incidentally diagnosed and 18% (6/34) presented with heart failure. Twenty-six (76%) children had main renal artery stenosis and 17 (50%) mid-aortic syndrome. Seventeen (50%) children showed intrarenal, six (18%) mesenteric, and three (9%) cerebrovascular involvement. Twenty patients underwent 45 percutaneous transluminal angioplasty procedures and seven children surgeries. In 44% of the 16 patients who underwent only percutaneous transluminal angioplasty blood pressure was normalized, 38% had improvement on same or decreased treatment and 19% showed no improvement. Complications were seen in 7.5% (5/66) of angiographies. In four of the seven (57%) children who underwent surgery blood pressure was normalized, two had improved (29%) and one unchanged (14%) blood pressure. CONCLUSION: In small children with renovascular hypertension below the age of 2 years, percutaneous transluminal angioplasty caused significant improvement in blood pressure with low complication profile. Surgery can be recommended where percutaneous transluminal angioplasty and medical treatments failed. WHAT IS KNOWN: • Renovascular hypertension is diagnosed in all age groups from a few weeks of life until adulthood. • Both angioplasty and surgery are significantly more difficult to perform in small children and the published information on short and long-term outcome in these children is very scarce. WHAT IS NEW: • Children below the age of two years can safely and successfully undergo selective renal angiography and also safely be treated with angioplasty. • We here present a large group of babies and infants where angioplasty and in some cases surgery effectively and safely improved their blood pressure.

Biopsy-proven Henoch-Schönlein purpura nephritis: a single center experience.

BACKGROUND: Knowledge on normal progress and treatment of Henoch-Schönlein purpura nephritis (HSPN) is limited. This study reviews outcome, clinical, pathological, and therapeutic factors affecting the prognosis of HSPN patients. METHODS: Forty-nine children with biopsy-confirmed HSPN diagnosed between September 2008 and 2018 were included. Demographics, clinical and laboratory data, treatment, and outcome were recorded at the time of biopsy, 3, 6, 12, and 24 months and at last visit. Clinical outcome was graded according to Meadow's criteria. RESULTS: The median age at time of biopsy was 10.1 years (IQR:5.7) and female/male ratio 24/25. At presentation, 40.8% of patients had nonnephrotic proteinuria, 18.4% nephrotic syndrome (NS), 4.1% nephritic syndrome (NephrS), and 36.7% NephrS+NS. There were 11 patients with an estimated glomerular filtration rate below 90 ml/min/1.73 m2. Biopsy specimens were classified according to International Study of Kidney Diseases in Children (ISKDC) and Oxford Classification MEST-C scoring systems. Forty-one patients received angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, 37 patients steroids, and 35 patients other immunosuppressive medications. At last visit, 24 patients had stage 1 chronic kidney disease (CKD), three stage 2 CKD, and two had stage 5 CKD. Neither clinical parameters nor ISKDC biopsy grade or treatment modalities effected the final outcome. The Oxford classification showed significantly increased segmental glomerulosclerosis in patients with unfavorable outcome. Favorable outcome was associated with shorter time from kidney involvement to biopsy and start of treatment. CONCLUSION: A large proportion of patients continued to show signs of CKD at last follow-up while only a small proportion developed stage 5 CKD.

Favipiravir use in children with COVID-19 and acute kidney injury: is it safe?

BACKGROUND: The rising number of infections due to Severe Acute Respiratory Syndrome Coronavirus-2 (popularly known as COVID-19) has brought to the fore new antiviral drugs as possible treatments, including favipiravir. However, there is currently no data regarding the safety of this drug in patients with kidney impairment. The aim of this paper, therefore, is to share our experience of the use of favipiravir in pediatric patients affected by COVID-19 with any degree of kidney impairment. METHODS: The study enrolled pediatric patients aged under 18 years and confirmed as suffering from COVID-19 and multisystem inflammatory syndrome in children (MIS-C) with any degree of kidney injury, who were treated with favipiravir at the time of admission. RESULTS: Out of a total of 11 patients, 7 were diagnosed with MIS-C and 4 with severe COVID-19. The median age of the cases was 15.45 (9-17.8) years and the male/female ratio was 7/4. At the time of admission, the median serum creatinine level was 1.1 mg/dl. Nine patients were treated with favipiravir for 5 days, and 2 patients for 5 days followed by remdesivir for 5-10 days despite kidney injury at the time of admission. Seven patients underwent plasma exchange for MIS-C while 2 severely affected cases underwent continuous kidney replacement therapy (CKRT) as well. One severe COVID-19 patient received plasma exchange as well as CKRT. Serum creatinine values returned to normal in mean 3.07 days. CONCLUSIONS: Favipiravir seems a suitable therapeutic option in patients affected by COVID-19 with kidney injury without a need for dose adjustment.

Clinical characteristics of childhood acute tubulointerstitial nephritis.

BACKGROUND: Acute tubulointerstitial nephritis (ATIN) is a rare cause of acute kidney injury in children that can lead to chronic kidney disease. The aim of this study was to describe the presenting features, etiology, and clinical characteristics of childhood ATIN, and to evaluate treatment modalities and renal outcomes. METHODS: The study included 38 patients who had been diagnosed with ATIN, were younger than 18 years old, and were admitted for at least 6 months of follow up. RESULTS: The median age at diagnosis was 13.1 years (range 1.2-16.6 years). The female / male ratio was 1.37. The most common symptoms were abdominal pain (65.7%) and nausea / vomiting (55.2%). Twenty-three of the patients had a history of drug intake (60.5%), and the most active drugs in the etiology were non-steroidal anti-inflammatory drugs (56.5%). Eleven patients were given steroid therapy due to severe kidney involvement and rapid increases in serum creatinine values, and ten of those patients were drug-related ATIN cases. Other patients were given symptomatic treatment. Four patients needed several sessions of dialysis due to the severity of their acute renal failure. The follow-up creatinine and estimated glomerular filtration rate levels were not statistically different between the symptomatic and corticosteroid treated groups (P > 0.05). CONCLUSIONS: Although our study was unable to show the beneficial effect of corticosteroid therapy on the extent of renal recovery, the use of steroids may be preferable in severe nephritis because of the rapid recovery of estimated glomerular filtration rate with corticosteroid therapy.

The changing resistance patterns of bacterial uropathogens in children.

BACKGROUND: Increased antimicrobial resistance is a problem in managing urinary tract infections (UTI). With this study we assessed the resistance patterns of urinary isolates in children with UTI between January 2017 and January 2018. METHODS: A retrospective cohort study was conducted. Among 5,443 isolates, a total of 776 UTI episodes in 698 patients were included. Patients' gender, age, voiding dysfunction, UTI history, prophylaxis status, and presence of vesicoureteral reflux were noted. Patients were divided into three age groups: group 1 for ages ≤12 months; group 2 for ages 13-60 months; and group 3 for ages >60 months. The susceptibilities of etiologic agents to different antimicrobials were explored. RESULTS: Median age was 54 months (range 1 month-21 years); male to female ratio was 1:5. The most common causative agent was Escherichia coli (83% of the cases), followed by Klebsiella pneumoniae (7.5%). Resistance to ampicillin (62.6%) and co-trimoxazole (39.8%) were remarkable in all isolates. Overall extended-spectrum beta-lactamase (ESBL) positivity was 23.5%. The highest resistance rates, higher ESBL positivity (28.6%), and K. pneumoniae frequency (13.5%) were observed in group 1. Ceftriaxone resistance was significantly low (0.5%) in the ESBL (-) group, which constituted the majority of the isolates. Higher resistance rates were observed among the patients on prophylaxis compared to those off prophylaxis (P < 0.001). CONCLUSION: Ceftriaxone can still be used for empirical treatment; however, initial urine culture results are crucial due to high ESBL positivity. Special consideration must be taken for patients under 1 year of age. Periodical surveillance studies are needed to explore the changing resistance patterns of uropathogens and modify treatment plans.

Proteinuria in pediatric renal transplant recipients.

Proteinuria has been shown to be an important and potentially treatable risk factor for graft loss. The aim of this study was to evaluate prevalence, etiology, and outcome of proteinuria during the follow-up of children with renal transplantation. We retrospectively reviewed the files of renal transplanted children between 2006 and 2016 in our center. All patients were interpreted with respect to the demographic data and clinical and laboratory features including information about proteinuria. Chi-square test and Mann-Whitney U test were used for analysis. Fifty-two children were eligible for the study. Proteinuria was observed in 34 (65%) and nephrotic range proteinuria was detected in 5 (9.6%) patients. Etiology of proteinuria could be identified in 21 patients. Acute rejection and uncontrolled hypertension were the most frequent causes of proteinuria. Proteinuria had resolved during the follow-up in 59% of the patients. We found that children with and without proteinuria had similar glomerular filtration rate at the end of 50 months of follow-up period. Proteinuria seems to be a common complication in renal transplant recipients. Graft functions can be preserved by immediate evaluation of increasing proteinuria, and by fixing treatable causes rapidly and efficiently during the follow-up in majority of the patients.

Retrospective analysis of simple and stage II renal cysts: Pediatric nephrology point of view.

BACKGROUND: Increased ultrasonography (US) use has been correlated with an increased incidence of pediatric renal cysts. For simple and stage II cysts, the malignancy risk is low in adulthood, no follow up is recommended; but there is no consensus on childhood management. Given that pediatric renal cysts may be manifestations of hereditary cystic diseases, a different approach and follow up should be taken for these patients. Herein we present the clinical characteristics and follow-up data of pediatric patients with simple and stage II renal cysts. METHODS: This cross-sectional study involved 57 children (mean age, 12.44 ± 3.65 years) with simple (n = 35) and stage II cysts (n = 22) who were diagnosed and followed at the present institution for ≥2 years. RESULTS: The median follow-up period was 2.84 years for simple and 3.10 years for stage II cysts. None of the patients developed complications. No change in cyst diameter was detected in 65.7% of simple or in 45.5% of stage II cysts, whereas 13 simple cysts (37.1%) and eight stage II cysts (36.4%) increased in diameter. The diameter change per year was significantly higher in the stage II cysts than in the simple cysts (P = 0.017). Overall, 13 patients (22%) had an estimated glomerular filtration rate <90 mL/min/1.73 m2 , and two patients had hypertension. CONCLUSION: Although the malignancy risk of simple and stage II kidney cysts is low for this age group, potential complications such as renal dysfunction, hypertension and hereditary cystic disease should be closely monitored.

Hypertension and improved left ventricular mass index in children after renal transplantation.

This study was conducted to evaluate the changes in BP and LVH after the transplantation and to evaluate the effect of BP changes in LVH. Forty-three pediatric renal transplant patients, with a mean age of 16.99 ± 3.88 years, were enrolled in this study. Twenty-three (53.5%) of the patients were male. Medical records for pretransplantation period (closest to the time of transplantation) and for post-transplantation period (9-12 months after transplantation) were reviewed. All the patients had BP measurements and echocardiographic evaluation in pre- and post-transplantation period. Hypertension was defined as an average systolic and/or diastolic BP that is ≥95th percentile for sex, age, and height. Although the number of patients with hypertension increased from 30 (69.76%) to 35 (81.4%), the number of patients with LVH decreased from 19 (44.1%) to 9 (20.9%) after the transplantation. Although the only significant difference in BP measurements was between the mean Z scores of 24 hour and nighttime mean DBP before and after the transplantation; the mean LVMI, and the prevalence of LVH was significantly lower after the transplantation. There was no significant correlation between the LVMI and the BP measurements. Even though hypertension may persist, there is significant improvement in LVH after renal transplantation.