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.

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.

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.

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.

Results in the ESPN/ERA-EDTA Registry suggest disparities in access to kidney transplantation but little variation in graft survival of children across Europe.

One of the main objectives of the European health policy framework is to ensure equitable access to high-quality health services across Europe. Here we examined country-specific kidney transplantation and graft failure rates in children and explore their country- and patient-level determinants. Patients under 20 years of age initiating kidney replacement therapy from January 2007 through December 2015 in 37 European countries participating in the ESPN/ERA-EDTA Registry were included in the analyses. Countries were categorized as low-, middle-, and high-income based on gross domestic product. At five years of follow-up, 4326 of 6909 children on kidney replacement therapy received their first kidney transplant. Overall median time from kidney replacement therapy start to first kidney transplantation was 1.4 (inter quartile range 0.3-4.3) years. The five-year kidney transplantation probability was 48.8% (95% confidence interval: 45.9-51.7%) in low-income, 76.3% (72.8-79.5%) in middle-income and 92.3% (91.0-93.4%) in high-income countries and was strongly associated with macro-economic factors. Gross domestic product alone explained 67% of the international variation in transplantation rates. Compared with high-income countries, kidney transplantation was 76% less likely to be performed in low-income and 58% less likely in middle-income countries. Overall five-year graft survival in Europe was 88% and showed little variation across countries. Thus, despite large disparities transplantation access across Europe, graft failure rates were relatively similar. Hence, graft survival in low-risk transplant recipients from lower-income countries seems as good as graft survival among all (low-, medium-, and high-risk) graft recipients from high-income countries.

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.

Molecular analysis of the AGXT gene in patients suspected with hyperoxaluria type 1 and three novel mutations from Turkey.

Primary hyperoxaluria type 1 (PH1) is a rare, autosomal recessive disease, caused by the defect of AGXT gene encoding hepatic peroxisomal alanine glyoxylateaminotransferase (AGT). This enzyme is responsible for the conversion of glyoxylate to glycine. The diagnosis of PH1 should be suspected in infants and children with nephrocalcinosis or nephrolithiasis. Early diagnosis and treatment is crucial in preventing disease progression to end stage kidney disease (ESKD). In this study, AGXT gene sequence analyses were performed in 82 patients who were clinically suspected (hyperoxaluria and nephrolithiasis or nephrocalcinosis with or without renal impairment) to have PH1. Disease causing mutations have been found in fifteen patients from thirteen families (18%). Novel mutations have been found (c.458T>A (p.L153X), c.733_734delAA (p.Lys245Valfs*11), c.52 C>T (p.L18F)) in three of 13 families. There were 3-year lag time between initial symptoms and the time of PH1 is suspected; additionally, 5.5-year lag time between initial symptoms and definitive diagnosis. Consanguinity was detected in 77% of the patients with mutation. After genetic diagnosis, one patient received combined kidney and liver transplantation. AGXT gene sequencing is now the choice of diagnosis of PH1 due to its non-invasive nature compared to liver enzyme assay. Early diagnosis and accurate treatment in PH1 is important for better patient outcomes.