Measurement of urinary protein in children

Proteinuria is an early hallmark of kidney disease and a major risk factor for systemic cardiovascular diseases. There are several methods to measure proteinuria, such as the urine dipstick test, 24-hour urinary protein excretion method, and spot urine for the protein-to-creatinine ratio. The urine dipstick test is simple but inaccurate. The 24-hour urinary protein excretion method is the gold standard; however, it is cumbersome, especially in children. Spot urine for the protein-to-creatinine ratio is simple and accurate, but has limitations. Specific urinary protein such as albumin can be measured instead of the total protein content. Tests should be avoided in situations that cause transient proteinuria or false-positive results. It should be performed correctly, and its limitations should be recognized and interpreted accurately.

Hypertensive crisis following mRNA COVID-19 vaccination in adolescents: two case reports

In response to the global coronavirus disease 2019 (COVID-19) pandemic, vaccines were developed and approved quickly. However, numerous cardiovascular adverse events have been reported. We present two adolescent cases who developed a hypertensive crisis following NT162b2 mRNA COVID-19 vaccination. Patient 1 was an 18-year-old male and his systolic blood pressure was 230 mmHg one day after the second vaccine. He was obese. No secondary cause of hypertension other than the vaccine was identified. Patient 2 was an 18-year-old male who complained with palpitation after the first vaccine. His blood pressure was 178/109 mmHg. He had autosomal dominant polycystic kidney disease. Both were treated with continuous infusion of labetalol followed by losartan, and blood pressure was controlled. Patient 2 received second vaccination and his blood pressure did not rise. It is warranted to measure blood pressure in adolescents at high risk of hypertension after NT162b2 mRNA COVID-19 vaccination.

Acute dural venous sinus thrombosis in a child with idiopathic steroid-dependent nephrotic syndrome: a case report

Nephrotic syndrome (NS) is a hypercoagulable state in which children are at risk of venous thromboembolism. A higher risk has been reported in children with steroid-resistant NS than in those with steroid-sensitive NS. The mortality rate of cerebral venous sinus thrombosis (CVST) is approximately 10% and generally results from cerebral herniation in the acute phase and an underlying disorder in the chronic phase. Our patient initially manifested as a child with massive proteinuria and generalized edema. He was treated with albumin replacement and diuretics, angiotensin-converting enzyme inhibitor, and deflazacort. Non-contrast computed tomography showed areas of hyperattenuation in the superior sagittal sinus when he complained of severe headache and vomiting. Subsequent magnetic resonance imaging revealed empty delta signs in the superior sagittal, lateral transverse, and sigmoid sinuses, suggesting acute CVST. Immediate anticoagulation therapy was started with unfractionated heparin, antithrombin III replacement, and continuous antiproteinuric treatment. The current report describes a life-threatening CVST in a child with steroid-dependent NS, initially diagnosed by contrast non-enhanced computed tomography and subsequently confirmed by contrast-enhanced magnetic resonance imaging, followed by magnetic resonance venography for recanalization, addressing successful treatment.

Incidence of Postnatal CMV Infection among Breastfed Preterm Infants:a Systematic Review and Meta-analysis

Background@#We performed a systematic review and meta-analysis to evaluate the incidence of breast milk-acquired cytomegalovirus (CMV) infection in preterm infants born to CMVseropositive mothers. @*Methods@#PubMed, Embase, and Cochrane Library databases were searched using the terms: (“breast feeding” or “breast milk” or “human milk” or “breast”) and (“HCMV” or “cytomegalovirus”) and (“infant, extremely premature” or “premature birth” or “newborn” or “neonate” or “low birth weight” or “very low birth weight” or “premature” or “preterm infant”). Studies that had information on CMV status and breast feeding were included in the meta-analysis. @*Results@#A total of 2,502 newborns from 19 studies were included in this meta-analysis. The rate of postnatally acquired CMV infection among breastfed infants with CMV-seropositive mothers was 16.5% (95% confidence interval [CI], 0.10–0.26; P < 0.001). The infection rate was 26% with fresh breast milk, 8% with a combined diet of fresh and freeze–thawed breast milk, and 11% with freeze–thawed breast milk. Among cases where the CMV status of breast milk was determined, CMV shedding into breast milk occurred in 80.5% (95% CI, 0.71–0.87; P < 0.001) of CMV seropositive mothers. The breast milk-acquired CMV infection rate among infants fed CMV-positive breast milk was 20.7% (95% CI, 0.14–0.30; P < 0.001). @*Conclusion@#This meta-analysis examined the rate of breast milk-acquired CMV infections in preterm infants with CMV-seropositive mothers; the CMV infection rate was higher in preterm infants fed fresh breast milk. Until further data are available, we cautiously suggest the use of freeze–thawed breast milk, rather than fresh breast milk, for preterm infants or very low birth weight infants.

Incidence of Postnatal CMV Infection among Breastfed Preterm Infants:a Systematic Review and Meta-analysis

Background@#We performed a systematic review and meta-analysis to evaluate the incidence of breast milk-acquired cytomegalovirus (CMV) infection in preterm infants born to CMVseropositive mothers. @*Methods@#PubMed, Embase, and Cochrane Library databases were searched using the terms: (“breast feeding” or “breast milk” or “human milk” or “breast”) and (“HCMV” or “cytomegalovirus”) and (“infant, extremely premature” or “premature birth” or “newborn” or “neonate” or “low birth weight” or “very low birth weight” or “premature” or “preterm infant”). Studies that had information on CMV status and breast feeding were included in the meta-analysis. @*Results@#A total of 2,502 newborns from 19 studies were included in this meta-analysis. The rate of postnatally acquired CMV infection among breastfed infants with CMV-seropositive mothers was 16.5% (95% confidence interval [CI], 0.10–0.26; P < 0.001). The infection rate was 26% with fresh breast milk, 8% with a combined diet of fresh and freeze–thawed breast milk, and 11% with freeze–thawed breast milk. Among cases where the CMV status of breast milk was determined, CMV shedding into breast milk occurred in 80.5% (95% CI, 0.71–0.87; P < 0.001) of CMV seropositive mothers. The breast milk-acquired CMV infection rate among infants fed CMV-positive breast milk was 20.7% (95% CI, 0.14–0.30; P < 0.001). @*Conclusion@#This meta-analysis examined the rate of breast milk-acquired CMV infections in preterm infants with CMV-seropositive mothers; the CMV infection rate was higher in preterm infants fed fresh breast milk. Until further data are available, we cautiously suggest the use of freeze–thawed breast milk, rather than fresh breast milk, for preterm infants or very low birth weight infants.

A Premature Baby with Severe Oligohydramnios and Hypotension: a Case Report of Renal Tubular Dysgenesis

Renal tubular dysgenesis (RTD) is a rare fatal disorder in which there is poor development of proximal tubules, leading to oligohydramnios and the Potter sequences. RTD occurs secondary to renin-angiotensin system (RAS) blockade during the early stages of fetal development or due to autosomal recessive mutation of genes in the RAS pathway. A boy born at 33+1 weeks due to cord prolapse was found to be anuric and hypotensive. Pregnancy was complicated by severe oligohydramnios from gestational age 28+4 weeks. Abdominal sonography revealed diffuse globular enlargement of both kidneys with increased cortical parenchymal echogenicity. Infantogram showed a narrow thoracic cage and skull X-ray showed large fontanelles and wide sutures suggestive of ossification delay. Basal plasma renin activity was markedly elevated and angiotensin-converting enzyme was undetectable. Despite adequate use of medications, peritoneal dialysis, and respiratory support, he did not recover and expired on the 23rd day of life. At first, autosomal recessive polycystic kidney disease was suspected, but severe oligohydramnios along with refractory hypotension, anuria, skull ossification delay and high renin levels made RTD suspicious. ACE gene analysis revealed compound heterozygous pathogenic variations of c.1454.dupC in exon 9 and c.2141dupA in exon 14, confirming RTD. Based on our findings, we propose that, although rare, RTD should be suspected in patients with severe oligohydramnios and refractory hypotension.

Pediatric Acute Kidney Injury: Focusing on Diagnosisand Management

Acute kidney injury (AKI) is common in critically ill children, and is associated withincreased mortality and long-term renal sequelae. The definition of pediatric AKIwas standardized based on elevation in serum creatinine levels or decrease inurine output; accordingly, epidemiological studies have ensued. Although newbiomarkers appear to detect AKI earlier and predict prognosis more accuratelythan traditional markers, they are not frequently used in clinical setting. There isno validated pharmacological intervention for AKI, so prevention and early detectionare the mainstays of treatment. For high risk or early stage AKI patients,optimization of volume status and blood pressure, avoidance of nephrotoxins,and sufficient nutritional support are necessary, and have been demonstrated tobe effective in preventing the occurrence of AKI and improving prognosis. Nevertheless,renal replacement therapy is needed when conservative care fails.

Serum uric acid in Korean children and adolescents: reference percentiles and association with metabolic syndrome

Purpose@#To establish age/sex-specific reference intervals for serum uric acid and to examine the associations between serum uric acid level and metabolic syndrome (MetS) and its components in Korean children and adolescents. @*Methods@#We analyzed data for 1,349 subjects aged 10 to 19 years from the Korea National Health and Nutrition Examination Survey 2016–2017. @*Results@#The mean uric acid levels were 5.9±1.3 mg/dL (interquartile range, 5.0–6.8 mg/dL) in males and 4.6±0.9 mg/dL (interquartile range, 3.9–5.2 mg/dL) in females. The mean uric acid level increased significantly from 10–13 years of age in males, but not in females. The overall prevalence of MetS was 5.9% (7.3% in males and 4.3% in females; P=0.022). The prevalences of MetS in the lowest, second, third, and highest quartiles of uric acid level were 4.4%, 3.3%, 6.1%, and 15.2%, respectively, in males (P for trend <0.001) and 1.9%, 0.0%, 4.1%, and 10.9%, respectively, in females (P for trend <0.001). Compared with the lowest quartile of uric acid level, the odds ratio (with 95% confidence interval) for MetS in the highest quartile was 2.897 (1.140–7.361) in males and 5.173 (1.459–18.342) in females. Subjects in the highest quartile exhibited increased risk for abdominal obesity and low high-density lipoprotein cholesterol in both sexes. @*Conclusion@#Serum uric acid level is positively associated with MetS and its components abdominal obesity and low high-density lipoprotein cholesterol.

Urological Problems in Patients with Menkes Disease

BACKGROUND: Menkes disease (MD) is a rare X-linked hereditary multisystemic disorder that is caused by dysfunction of copper metabolism. Patients with MD typically present with progressive neurodegeneration, some connective tissue abnormalities, and characteristic “kinky” hair. In addition, various types of urological complications are frequent in MD because of underlying connective tissue abnormalities. In this study, we studied the clinical features and outcomes of MD, focusing on urological complications. METHODS: A total of 14 unrelated Korean pediatric patients (13 boys and 1 girl) with MD were recruited, and their phenotypes and genotypes were analyzed by retrospective review of their medical records. RESULTS: All the patients had early-onset neurological deficit, including developmental delay, seizures, and hypotonia. The girl patient showed normal serum copper and ceruloplasmin levels as well as milder symptoms. Mutational analysis of the ATP7A gene revealed 11 different mutations in 12 patients. Bladder diverticula was the most frequent urological complication: 8 (57.1%) in the 14 patients or 8 (72.7%) in the 11 patients who underwent urological evaluation. Urological imaging studies were performed essentially for the evaluation of accompanying urinary tract infections. Four patients had stage II chronic kidney disease at the last follow-up. CONCLUSION: Urologic problems occurred frequently in MD, with bladder diverticula being the most common. Therefore, urological imaging studies and appropriate management of urological complications, which may prevent or reduce the development of urinary tract infections and renal parenchymal damage, are required in all patients with MD.

Primary Hyperoxaluria in Korean Pediatric Patients

BACKGROUND: Primary hyperoxaluria (PH), a rare inborn error of glyoxylate meta bolism causing overproduction of oxalate, is classified into three genetic subgroups: type 1–3 (PH1–PH3) caused by AGXT, GRHPR , and HOGA1 gene mutations, respectively. We performed a retrospective case series study of Korean pediatric patients with PH.METHODS: In total, 11 unrelated pediatric patients were recruited and their phenotypes and genotypes were analyzed by a retrospective review of their medical records.RESULTS: Mutational analyses revealed biallelic AGXT mutations (PH1) in nine patients and a single heterozygous GRHPR and HOGA1 mutation in one patient each. The c.33dupC was the most common AGXT mutation with an allelic frequency of 44%. The median age of onset was 3 months (range, 2 months-3 years), and eight patients with PH1 presented with end stage renal disease (ESRD). Patients with two truncating mutations showed an earlier age of onset and more frequent retinal involvement than patients with one truncating mutation. Among eight PH1 patients presenting with ESRD, five patients were treated with intensive dialysis followed by liver transplantation (n=5) with/without subsequent kidney transplantation (n=3).CONCLUSION: Most patients presented with severe infantile forms of PH. Patients with two truncating mutations displayed more severe phenotypes than those of patients with one truncating mutation. Sequential liver and kidney transplantation was adopted for PH1 patients presenting with ESRD. A larger nation-wide multicenter study is needed to confirm the genotype-phenotype correlations and outcomes of organ transplantation.

A Pediatric Case of a D-Penicillamine Induced ANCA-associated Vasculitis Manifesting a Pulmonary-Renal Syndrome

D-penicillamine has been reported to cause antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis presenting as rapidly progressive glomerulonephritis or pulmonary-renal syndrome mostly in adults. We report a pediatric case of D-penicillamine induced ANCA-associated vasculitis that manifests as a pulmonary-renal syndrome with a mild renal manifestation. A 13-year-old girl who has been taking D-penicillamine for five years under the diagnosis of Wilson disease visited the emergency room because of hemoptysis and dyspnea. She had diffuse pulmonary hemorrhage, microscopic hematuria, and proteinuria. Myeloperoxidase ANCA was positive, and a renal biopsy revealed pauci-immune crescentic glomerulonephritis. Under the diagnosis of D-penicillamine-induced ANCA-associated vasculitis, D-penicillamine was switched to trientine, and the patient was treated with plasmapheresis, glucocorticoid, cyclophosphamide, and mycophenolate mofetil. Pulmonary hemorrhage improved rapidly followed by the disappearance of the hematuria and proteinuria five months later.

Erratum: Correction of Error in Result: Urological Problems in Patients with Menkes Disease

The authors regret that there was an important error in the results in Table 1; the ATP7A mutations detected in Patients 2 and 14 were incorrectly noted.

Reninoma: a rare cause of curable hypertension / 소아과

The most common type of refractory hypertension found in children is secondary hypertension, which is a potentially curable disease. Reninoma, a renin-secreting juxtaglomerular cell tumor, is a rare cause of severe hypertension that is usually diagnosed in adolescents and young adults. Surgical resection of the tumor completely cures the hypertension of patients with reninoma. The typical clinical presentation of reninoma includes hypokalemia, metabolic alkalosis, and features secondary to the increased activation of the renin-angiotensin system without renal artery stenosis. We report a case of reninoma in a female adolescent with a typical clinical presentation, in which surgical removal of the tumor completely cured hypertension. We discuss here the clinical features, imaging studies, and immunohistochemical examination of the tumor used to establish the diagnosis of reninoma and for the management of the condition.

Acute kidney injury associated with Yersinia pseudotuberculosis infection: Forgotten but not gone

BACKGROUND: Yersinia pseudotuberculosis is known to cause fever, gastroenteritis, or acute kidney injury (AKI). There have been several Y. pseudotuberculosis infection outbreaks to date associated with ingestion of contaminated food or unsterile water. While this disease was considered to have practically been eradicated with the improvement in public health, we encountered several cases of AKI associated with Yersinia infection. METHODS: We retrospectively collected data from medical records of patients with suspected Y. pseudotuberculosis infection who visited Seoul National University Children’s Hospital in 2017. RESULTS: There were nine suspected cases of Yersinia infection (six males and three females; age range 2.99–12.18 years). Among them, five cases occurred in May, and seven patients were residing in the metropolitan Seoul area. Three patients had history of drinking mountain water. Every patient first presented with fever for a median of 13 days, followed by gastrointestinal symptoms and oliguria. Imaging studies revealed mesenteric lymphadenitis, terminal ileum wall thickening, and increased renal parenchymal echogenicity. Creatinine levels increased to 5.72 ± 2.18 mg/dL. Urinalysis revealed sterile pyuria, proteinuria, and glycosuria. Oliguria continued for 4 to 17 days, and two patients required dialysis; however, all of them recovered from AKI. Mucocutaneous manifestations developed later. In the diagnostic work-up, Yersinia was isolated from the stool culture in one patient. Anti-Yersinia immunoglobulin (Ig) A and IgG were positive in 6 patients. CONCLUSION: Y. pseudotuberculosis infection is an infrequent cause of interstitial nephritis presenting with AKI. When a patient presents with fever, gastroenteritis, and AKI not resolving despite hydration, the clinician should suspect Y. pseudotuberculosis infection.

Acute kidney injury and continuous renal replacement therapy in children; what pediatricians need to know / 소아과

Acute kidney injury (AKI) is characterized by abrupt deterioration of renal function, and its diagnosis relies on creatinine measurements and urine output. AKI is associated with higher morbidity and mortality, and is a risk factor for development of chronic kidney disease. There is no proven medication for AKI. Therefore, prevention and early detection are important. Physicians should be aware of the risk factors for AKI and should monitor renal function in high-risk patients. Management of AKI includes optimization of volume status and renal perfusion, avoidance of nephrotoxic agents, and sufficient nutritional support. Continuous renal replacement therapy is widely available for critically ill children, and this review provides basic information regarding this therapy. Long-term follow-up of patients with AKI for renal function, blood pressure, and proteinuria is recommended.

A Pediatric Case of Inflammatory Bowel Disease with Renal Amyloidosis

Amyloidosis is a rare disease that results from the deposition of extracellular protein in various body tissues, causing progressive organ dysfunction. Secondary renal amyloidosis is a rare but serious complication of chronic inflammatory bowel disease, particularly in patients with Crohn's disease or ulcerative colitis. We report a case of secondary renal amyloidosis in a pediatric patient who reported a 16-year history of “very early onset inflammatory bowel disease”. Intensive treatment including repeated infliximab infusions improved clinical parameters of inflammatory bowel disease, although renal dysfunction showed progression. Amyloidosis should be considered in patients with IBD, particularly if they suffered disease progression.

Acute kidney injury in childhood-onset nephrotic syndrome: Incidence and risk factors in hospitalized patients

BACKGROUND: Nephrotic syndrome (NS) is the most common glomerulopathy in children. Acute kidney injury (AKI) is a common complication of NS, caused by severe intravascular volume depletion, acute tubular necrosis, interstitial nephritis, or progression of NS. However, the incidence and risk factors of childhood-onset NS in Korea are unclear. Therefore, we studied the incidence, causes, and risk factors of AKI in hospitalized Korean patients with childhood-onset NS. METHODS: We conducted a retrospective review of patients with childhood-onset NS who were admitted to our center from January 2015 to July 2017. Patients with decreased renal function or hereditary/secondary NS, as well as those admitted for management of other conditions unrelated to NS, were excluded. RESULTS: During the study period, 65 patients with idiopathic, childhood-onset NS were hospitalized 90 times for management of NS or its complications. Of these 90 cases, 29 met the Kidney Disease Improving Global Outcomes criteria for AKI (32.2%). They developed AKI in association with infection (n = 12), NS aggravation (n = 11), dehydration (n = 3), and intravenous methylprednisolone administration (n = 3). Age ≥ 9 years at admission and combined use of cyclosporine and renin-angiotensin system inhibitors were risk factors for AKI. CONCLUSION: AKI occurred in one-third of the total hospitalizations related to childhood-onset NS, owing to infection, aggravation of NS, dehydration, and possibly high-dose methylprednisolone treatment. Age at admission and use of nephrotoxic agents were associated with AKI. As the AKI incidence is high, AKI should be considered during management of high-risk patients.

Long-term repeated rituximab treatment for childhood steroid-dependent nephrotic syndrome

BACKGROUND: Rituximab (RTX) can be used as a rescue therapy for steroid-dependent nephrotic syndrome (SDNS). However, the efficacy and safety of long-term, repeated use of RTX are not established. This study was conducted to assess the efficacy and safety of long-term, repeated RTX treatment in children. METHODS: Eighteen consecutive child patients with SDNS who were treated with three or more cycles of RTX for one year or longer were recruited, and their medical records were retrospectively reviewed. RESULTS: The patients were followed for 4.7 ± 1.9 years and received 5.2 ± 2.3 cycles of RTX over 2.8 ± 1.1 years. Approximately 70% of the additional RTX cycles were administered due to recovery of B-cells without relapse. The relapse rate decreased from 3.4 ± 2.0 per year initially to 0.4 ± 0.8 per year at the third year after RTX treatment. Approximately 10% of the RTX infusions were accompanied by mild infusion reactions. Eight patients showed sustained remission without any oral medication after the last cycle of RTX, while 10 patients had one or more episodes of relapse after the last cycle of RTX. The relapse rate in the latter group decreased from 2.8 ± 1.5 per year before RTX treatment to 1.3 ± 0.8 per year after cessation of RTX treatment. No significant differences in clinical parameters were found between the two groups. CONCLUSION: This retrospective study showed that pre-emptive and long-term, repeated RTX treatment is relatively effective and safe in children with SDNS. However, well-designed prospective studies are needed to confirm these findings.

Relationship of Renal Echogenicity with Renal Pathology and Function

PURPOSE: Renal ultrasonography has been widely used in children with renal disease. However, the relationship of renal echogenicity with renal pathology and function in children is not well known. METHODS: Ultrasound examination was performed in 75 patients undergoing renal biopsy for suspected renal disease in Konkuk University Medical Center from August 2005 to November 2015. We compared renal echogenicity to pathologic findings and renal function. Renal echogenicity was scored as 0 to 2 by comparing adjacent liver echogenicity. Three histologic characteristics were evaluated: glomerular changes, interstitial infiltration or fibrosis, and tubular atrophy. These were graded as 0 to 3, according to increasing severity. Laboratory results included urine albumin excretion and estimated glomerular filtration rate (eGFR). RESULTS: Among pathologic findings, renal echogenicity revealed a positive correlation with interstitial infiltration or fibrosis (r=0.259, P=0.025), and with tubular atrophy (r=0.268, P=0.02). Renal echogenicity and glomerular changes were not correlated. Renal echogenicity showed a positive correlation with microalbuminuria (r=0.283, P=0.014), but a negative correlation with eGFR (r=-0.352, P=0.002). CONCLUSION: Increased renal echogenicity suggested severe interstitial infiltration or fibrosis and tubular atrophy among the pathologic findings. Moreover, increased echogenicity is correlated with increased urine albumin excretion and decreased eGFR. Echogenicity on ultrasonography is useful for determining the status of renal pathology and function.

Relationship of Renal Echogenicity with Renal Pathology and Function

PURPOSE: Renal ultrasonography has been widely used in children with renal disease. However, the relationship of renal echogenicity with renal pathology and function in children is not well known. METHODS: Ultrasound examination was performed in 75 patients undergoing renal biopsy for suspected renal disease in Konkuk University Medical Center from August 2005 to November 2015. We compared renal echogenicity to pathologic findings and renal function. Renal echogenicity was scored as 0 to 2 by comparing adjacent liver echogenicity. Three histologic characteristics were evaluated: glomerular changes, interstitial infiltration or fibrosis, and tubular atrophy. These were graded as 0 to 3, according to increasing severity. Laboratory results included urine albumin excretion and estimated glomerular filtration rate (eGFR). RESULTS: Among pathologic findings, renal echogenicity revealed a positive correlation with interstitial infiltration or fibrosis (r=0.259, P=0.025), and with tubular atrophy (r=0.268, P=0.02). Renal echogenicity and glomerular changes were not correlated. Renal echogenicity showed a positive correlation with microalbuminuria (r=0.283, P=0.014), but a negative correlation with eGFR (r=-0.352, P=0.002). CONCLUSION: Increased renal echogenicity suggested severe interstitial infiltration or fibrosis and tubular atrophy among the pathologic findings. Moreover, increased echogenicity is correlated with increased urine albumin excretion and decreased eGFR. Echogenicity on ultrasonography is useful for determining the status of renal pathology and function.