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.

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

BACKGROUND AND HYPOTHESIS: IgA vasculitis with nephritis (IgAVN) is the most common vasculitis in children. Treatment recommendations are, due to a lack of evidence, based on expert opinion resulting in variation. The aim of this study was to describe clinical presentation, treatment and outcome of an extremely large cohort of children with biopsy proven IgAVN 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 analyzed 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 (IQR 2-6.2). At last follow up, 29% of patients had an eGFR < 90 ml/min/1.73m2, 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 to be 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.

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.

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.

The outcomes of renin-angiotensin-aldosterone system inhibition and immunosuppressive therapy in children with X-linked Alport syndrome.

BACKGROUND: Alport syndrome (AS) is characterized by progressive kidney disease. There is increasing evidence that renin-angiotensin-aldosterone system (RAAS) inhibition delays chronic kidney disease (CKD) while the effectiveness of immunosuppressive (IS) therapy in AS is still uncertain. In this study, we aimed to analyze the outcomes of pediatric patients with X-linked AS (XLAS) who received RAAS inhibitors and IS therapy. METHODS: Seventy-four children with XLAS were included in this multicenter study. Demographic features, clinical and laboratory data, treatments, histopathological examinations, and genetic analyses were analyzed retrospectively. RESULTS: Among 74 children, 52 (70.2%) received RAAS inhibitors, 11 (14.9%) received RAAS inhibitors and IS, and 11 (14.9%) were followed up without treatment. During follow-up, glomerular filtration rate (GFR) decreased < 60 ml/min/1.73 m2 in 7 (9.5%) of 74 patients (M/F=6/1). In male patients with XLAS, kidney survival was not different between RAAS and RAAS+IS groups (p=0.42). The rate of progression to CKD was significantly higher in patients with nephrotic range proteinuria and nephrotic syndrome (NS), respectively (p=0.006, p=0.05). The median age at the onset of RAAS inhibitors was significantly higher in male patients who progressed to CKD (13.9 vs 8.1 years, p=0.003). CONCLUSIONS: RAAS inhibitors have beneficial effects on proteinuria and early initiation of therapy may delay the progression to CKD in children with XLAS. There was no significant difference between the RAAS and RAAS+IS groups in kidney survival. AS patients presenting with NS or nephrotic range proteinuria should be followed up more carefully considering the risk of early progression to CKD.

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.

Alemtuzumab as a Successful Antirejection Therapy: Experience in a Pediatric Renal Transplant Patient.

Alemtuzumab is a monoclonal antibody against CD52 that is being increasingly used in renal transplantation as a lymphocyte-depleting agent. Data on alemtuzumab use in resistant rejection episodes are scarce, especially in children. Here, we present a 14-year-old renal transplant patient with acute cellular and humoral rejection who was treated with pulse steroids, plasmapheresis, and intravenous immunoglobulin with no success. He had 2 previous rejection episodes that were treated with antithymocyte globulin. In the third episode, alemtuzumab was given as a rescue therapy, and the patient benefited from the treatment. No complications were observed. Alemtuzumab can be a treatment option in pediatric patients with refractory rejection episodes.

Two tales of LPIN1 deficiency: from fatal rhabdomyolysis to favorable outcome of acute compartment syndrome.

LPIN1 deficiency is an autosomal recessive disease caused by biallelic mutations in LPIN1, where impaired fatty acid metabolism leads to stress in skeletal muscle, resulting in severe rhabdomyolysis, often triggered by fever, exercise, fasting, and anesthesia. It is the second most common cause of severe, recurrent episodes of rhabdomyolysis in early childhood which can result in serious morbidity and mortality. To date, 71 patients have been published in 20 clinical studies in the form of case series. We describe two previously unreported cases, one with a novel LPIN1 mutation that resulted in mortality, and another, to the best of our knowledge, with the first reported compartment syndrome managed with a favorable outcome in this disorder. Recognition of the complications including ventricular arrythmias, acute renal failure and compartment syndrome on the severe end of the spectrum may change the outcome and prognosis of this devastating condition.

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.

Clinical spectrum of immunoglobulin A vasculitis in children and determining the best timing of urine examination to predict renal involvement.

BACKGROUND: Immunoglobulin A (IgA) vasculitis (also known as Henoch-Schonlein purpura) is the most common small vessel vasculitis of childhood. The long-term prognosis depends on renal involvement. The aim of this study was to evaluate the risk factors associated with renal involvement in children with IgA vasculitis and to investigate the best timing of urine examination to predict the presence of renal involvement at the sixth month after the diagnosis. METHODS: In this prospective observational study, medical records, demographic data, clinical findings, laboratory tests, and urine microscopic examinations of pediatric patients diagnosed with IgA vasculitis were evaluated to identify potential risk factors associated with renal involvement. RESULTS: A total of 178 patients with a median age of 6 years were involved in the study. Renal involvement was found in 24 (13.5%) patients. Most of the patients (85.7%), whose urine examination was found to be abnormal at the sixth month after the diagnosis, also had abnormalities in the first month urine examination. Factors significantly associated with renal involvement were as follows: older age, presence of hematuria and or proteinuria in the first month urine examination and patients who presented the disease in the spring season. Multivariate logistic regression analysis showed age ≥8 years (p = 0.005), the season of onset (p = 0.025), serum creatinine levels (p = 0.016), and abnormal urine examinations at the first-month visits (p = 0.005) significantly increased the risk of renal involvement. CONCLUSION: This study has demonstrated that the optimal date to predict the presence of hematuria and/or proteinuria in the sixth month is the urine examination performed in the first month of the disease. Therefore, we think that patients with IgA vasculitis who show a presence of hematuria and/or proteinuria in the first-month urine examination should be followed more closely.

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.

Infantile systemic lupus erythematous presenting as nephrotic syndrome in a 12-month-old boy: a case report.

BACKGROUND: Systemic lupus erythematous (SLE) is extremely rare in infants and has been reported to be a much more severe disease with higher prevalence of critical organ involvement. Herein we present the clinical and laboratory features of infantile SLE (iSLE) with an onset of nephrotic syndrome (NS) during the first year of life. CASE: A 12-month-old boy was suffering from generalized edema for two months. He had thrombocytopenia, hemolytic anemia with positive direct and indirect Coombs tests and proteinuria of nephrotic-range. Other laboratory studies revealed slightly decreased C3, low C1q and normal ANA and C4 levels; anti-phospholipid and anti-cardiolipin antibodies were also found to be negative. Renal biopsy revealed Class IV lupus nephritis. The patient also suffered from massive pulmonary thromboembolism. Complete remission was achieved with steroid, cyclophosphamide, mycophenolate mofetil and anticoagulant therapy. CONCLUSION: iSLE should be kept in mind especially in infantile NS with multisystem involvement. Renal biopsy is mandatory for early diagnosis. Although the disease was reported to have poor prognosis, complete remission could be achieved with intensive immunosuppressive therapy.

C3 glomerulopathy: experience of a pediatric nephrology center.

Background: C3 glomerulopathy (C3G) is an uncommon disease characterized by the deposition of complement factors in the glomeruli due to overactivation and dysregulation of the alternative pathway of complement.Objectives: This study aimed to describe the clinicopathological features, laboratory testing, clinical course, treatment, and outcomes of pediatric patients with C3G.Patients and Methods: We reviewed retrospectively the laboratory testing, kidney biopsy reports, and clinical features of 18 patients at our hospital from 2007 to 2019.Results: There were 18 cases, and the majority of the patients were girls (61.1%). The mean age at diagnosis was 11.3 ± 3.7 (5-17) years, and nephritic-nephrotic syndrome presentation in patients was more common (11 cases, 61.1%). Hematuria was found in 66.7% of the patients, of which the majority had microscopic hematuria (58.3%). Hypertension was observed in 10 (55.6%) patients. The mean glomerular filtration rate (eGFR) was 95.7 ± 47.3 mL/min/1.73 m2, and 24-h urinary protein excretion was 76.2 ± 48.6 mg/m2/h. Sixteen patients (88.9%) received renin-angiotensin-aldosterone system blockers (RASB), and two of them were taking RASB only. The majority of patients (83.3%) were treated with immunosuppressive therapy. Eculizumab was also given to one of them. At the last follow-up, two patients had levels of less than 60 mL/min/1.73 m2 for eGFR. Seven patients with immunosuppressive treatment achieved complete remission.Conclusion: C3G shows a variable clinical presentation and response to immunosuppressive therapy. In the present study, we observed that the most common presentation was nephritic and/or nephrotic syndrome and partially responded to treatment to RASB and immunosuppressants.

Gastric duplication cyst in an infant with Finnish-type congenital nephrotic syndrome: concurrence or coincidence?

Congenital nephrotic syndrome (CNS) is a rare disorder characterized by massive proteinuria and marked edema manifesting in utero or during the first 3 months of life. CNS can be caused by congenital infections, allo-immune maternal disease or due to the genetic defects of podocyte proteins most commonly NPHS1. Here we present a case of Finnish-type congenital nephrotic syndrome along with feeding problems and abdominal distention which was diagnosed during follow-up as a gastric-duplication cyst with a novel mutation in the nephrin gene. CNS feeding problems are attributed mainly to primary disease but in literature there are case reports of patients with CNS and hypertrophic pyloric stenosis. NPHS1 is also expressed in the stomach tissue. Physicians should be aware of this rare extra-renal manifestation or coincidence of this rare disease.

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.