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1.  Syndrome of Inappropriate Antidiuretic Hormone Secretion and Cerebral/Renal Salt Wasting Syndrome: Similarities and Differences 
Hyponatremia (sodium levels of <135 mEq/L) is one of the most common electrolyte imbalances in clinical practice, especially in patients with neurologic diseases. Hyponatremia can cause cerebral edema and brain herniation; therefore, prompt diagnosis and proper treatment is important in preventing morbidity and mortality. Among various causes of hyponatremia, diagnosing syndrome of inappropriate antidiuretic hormone secretion (SIADH) and cerebral/renal salt wasting syndrome (C/RSW) is difficult due to many similarities. SIADH is caused by excess of renal water reabsorption through inappropriate antidiuretic hormone secretion, and fluid restriction is the treatment of choice. On the other hand, C/RSW is caused by natriuresis, which is followed by volume depletion and negative sodium balance and replacement of water and sodium is the mainstay of treatment. Determinating volume status in hyponatremic patients is the key point in differential between SIADH and C/RSW. However, in most situations, differential diagnosis of these two diseases is difficult because they overlap in many clinical and laboratory aspects, especially to assess differences in volume status of these patients. Although distinction between the SIADH and C/RSW is difficult, improvement of hypouricemia and an increased fractional excretion of uric acid after the correction of hyponatremia in SIADH, not in C/RSW, may be one of the helpful points in discriminating the two diseases. In this review, we compare these two diseases regarding the pathophysiologic mechanisms, diagnosis, and therapeutic point of view.
PMCID: PMC4302789  PMID: 25657991
hyponatremia; syndrome of inappropriate antidiuretic hormone secretion; cerebral/renal salt wasting syndrome; volume status; fractional excretion of urate
2.  Inflammation and hyponatremia: an underrecognized condition? 
Korean Journal of Pediatrics  2013;56(12):519-522.
Timely diagnosis of hyponatremia is important for preventing potential morbidity and mortality as it is often an indicator of underlying disease. The most common cause of eurvolemic hyponatremia is the syndrome of inappropriate antidiuretic hormone (SIADH) secretion. Recent studies have demonstrated that proinflammatory cytokines such as interleukin (IL) 1β and IL-6 are involved in the development of hyponatremia, a condition that is associated with severe inflammation and is related to antidiuretic hormone (ADH) secretion. Serum sodium levels in hyponatremia are inversely correlated with the percentage of neutrophils, C-reactive protein, and N-terminal-pro brain type natriuretic peptide. Additionally, elevated levels of serum IL-6 and IL-1β are found in inflammatory diseases, and their levels are higher in patients with hyponatremia. Because it is significantly correlated with the degree of inflammation in children, hyponatremia could be used as a diagnostic marker of pediatric inflammatory diseases. Based on available evidence, we hypothesize that hyponatremia may be associated with inflammatory diseases in general. Understanding the mechanisms responsible for augmented ADH secretion during inflammation, monitoring patient sodium levels, and selecting the appropriate intravenous fluid treatment are important components that may lower the morbidity and mortality of patients in a critical condition.
PMCID: PMC3885786  PMID: 24416046
Hyponatremia; Inappropriate ADH Syndrome; Cytokines; Inflammatory disease; Critical condition
3.  Outcomes of Peritonitis in Children on Peritoneal Dialysis: A 25-Year Experience at Severance Hospital 
Yonsei Medical Journal  2013;54(4):983-989.
Relatively little is known on the microbiology, risk factors and outcomes of peritoneal dialysis (PD)-associated peritonitis in Korean children. We performed this study in order to evaluate the incidence, treatment and clinical outcomes of peritonitis in pediatric PD patients at Severance Hospital.
Materials and Methods
We analyzed data from 57 PD patients younger than 18 years during the period between June 1, 1986 and December 31, 2011. The collected data included gender, age at commencement of PD, age at peritonitis, incidence of peritonitis, underlying causes of end stage renal disease, microbiology of peritonitis episodes, antibiotics sensitivity, modality and outcomes of PD.
We found 56 episodes of peritonitis in 23 of the 57 PD patients (0.43 episodes/patient-year). Gram-positive bacteria were the most commonly isolated organisms (40 episodes, 71.4%). Peritonitis developed in 17 patients during the first 6 months following initiation of PD (73.9%). Peritonitis episodes rarely resulted in relapse or the need for permanent hemodialysis and no patient deaths were directly attributable to peritonitis. Antibiotic regimens included cefazolin+tobramycin from the years of 1986 to 2000 and cefazolin+ceftazidime from the years of 2001 to 2011. While antibiotic therapy was successful in 48 episodes (85.7%), the treatment was ineffective in 8 episodes (14.3%). The rate of continuous ambulatory PD (CAPD) peritonitis was statistically higher than that of automated PD (APD) (p=0.025).
Peritonitis was an important complication of PD therapy and we observed a higher incidence of PD peritonitis in patients with CAPD when compared to APD.
PMCID: PMC3663235  PMID: 23709435
Peritoneal dialysis; peritonitis; continuous ambulatory peritoneal dialysis; automated peritoneal dialysis; children
4.  Dense Deposit Disease in Korean Children: A Multicenter Clinicopathologic Study 
Journal of Korean Medical Science  2012;27(10):1215-1221.
The purpose of this study was to investigate the clinical, laboratory, and pathologic characteristics of dense deposit disease (DDD) in Korean children and to determine whether these characteristics differ between Korean and American children with DDD. In 2010, we sent a structured protocol about DDD to pediatric nephrologists throughout Korea. The data collected were compared with previously published data on 14 American children with DDD. Korean children had lower 24-hr urine protein excretion and higher serum albumin levels than American children. The light microscopic findings revealed that a higher percentage of Korean children had membranoproliferative glomerulonephritis patterns (Korean, 77.8%; American, 28.6%, P = 0.036), whereas a higher percentage of American children had crescents (Korean, 0%; American, 78.6%, P < 0.001). The findings from the electron microscopy revealed that Korean children were more likely to have segmental electron dense deposits in the lamina densa of the glomerular basement membrane (Korean, 100%; American, 28.6%, P = 0.002); mesangial deposit was more frequent in American children (Korean, 66.7%; American, 100%, P = 0.047). The histological findings revealed that Korean children with DDD were more likely to show membranoproliferative glomerulonephritis patterns than American children. The degree of proteinuria and hypoalbuminemia was milder in Korean children than American children.
PMCID: PMC3468759  PMID: 23091320
Dense Deposit Disease; Membranoproliferative Glomerulonephritis; Electron-Dense Deposit
5.  Cerebral Salt Wasting Treated with Fludrocortisone in a 17-Year-Old Boy 
Yonsei Medical Journal  2012;53(4):859-862.
Cerebral salt wasting is characterized by inappropriate natriuresis and volume contraction with associated cerebral pathology. It is distinct from the syndrome of inappropriate antidiuretic hormone secretion, which is characterized by inappropriate retention of free water. We report a patient with a porencephalic cyst who developed cerebral salt wasting. His initial treatment was supplementation of water and salt, which did not improve natriuresis or volume contraction. Fludrocortisone administration effectively managed the cerebral salt wasting.
PMCID: PMC3381498  PMID: 22665358
Cerebral salt wasting; hyponatremia; fludrocortisone
6.  Acute treatment of hyperammonemia by continuous renal replacement therapy in a newborn patient with ornithine transcarbamylase deficiency 
Korean Journal of Pediatrics  2011;54(10):425-428.
Ornithine transcarbamylase (OTC) deficiency is well known as the most common inherited disorder of the urea cycle, and 1 of the most common causes of hyperammonemia in newborns. We experienced a case of a 3-day-old boy with OTC deficiency who appeared healthy in the first 2 days of life but developed lethargy and seizure soon afterwards. His serum ammonia level was measured as >1700 µg/dL (range, 0 to 45 µg/dL). Continuous renal replacement therapy (CRRT) in the mode of continuous venovenous hemodiafiltration was immediately applied to correct the raised ammonia level. No seizure occurred after the elevated ammonia level was reduced. Therefore, CRRT should be included as 1 of the treatment modalities for newborns with inborn errors of metabolism, especially hyperammonemia. Here, we report 1 case of successful treatment of hyperammonemia by CRRT in a neonate with OTC deficiency.
PMCID: PMC3250597  PMID: 22232626
Ornithine transcarbamylase deficiency; Hyperammonemia; Continuous renal replacement therapy; Infant; Newborn
7.  Complications of nephrotic syndrome 
Korean Journal of Pediatrics  2011;54(8):322-328.
Nephrotic syndrome (NS) is one of the most common glomerular diseases that affect children. Renal histology reveals the presence of minimal change nephrotic syndrome (MCNS) in more than 80% of these patients. Most patients with MCNS have favorable outcomes without complications. However, a few of these children have lesions of focal segmental glomerulosclerosis, suffer from severe and prolonged proteinuria, and are at high risk for complications. Complications of NS are divided into two categories: disease-associated and drug-related complications. Disease-associated complications include infections (e.g., peritonitis, sepsis, cellulitis, and chicken pox), thromboembolism (e.g., venous thromboembolism and pulmonary embolism), hypovolemic crisis (e.g., abdominal pain, tachycardia, and hypotension), cardiovascular problems (e.g., hyperlipidemia), acute renal failure, anemia, and others (e.g., hypothyroidism, hypocalcemia, bone disease, and intussusception). The main pathomechanism of disease-associated complications originates from the large loss of plasma proteins in the urine of nephrotic children. The majority of children with MCNS who respond to treatment with corticosteroids or cytotoxic agents have smaller and milder complications than those with steroid-resistant NS. Corticosteroids, alkylating agents, cyclosporin A, and mycophenolate mofetil have often been used to treat NS, and these drugs have treatment-related complications. Early detection and appropriate treatment of these complications will improve outcomes for patients with NS.
PMCID: PMC3212701  PMID: 22087198
Nephrotic syndrome; Complications; Proteinuria; Child
8.  Effects of Cyclosporin A Therapy Combined with Steroids and Angiotensin Converting Enzyme Inhibitors on Childhood IgA Nephropathy 
Journal of Korean Medical Science  2010;25(5):723-727.
To evaluate the effects of cyclosporin A (CyA) on clinical outcome and pathologic changes in children with IgA nephropathy (IgAN), we retrospectively evaluated 14 children (mean age 8.9±2.9 yr; eight males, six females) who were treated with CyA and steroids. The starting dose of CyA was 5 mg/kg per day, and the drug level was maintained at 100-200 ng/mL. The mean CyA level was 183.8±48.3 ng/mL (range 120.7-276.0 ng/mL) and the mean duration of CyA therapy was 10.9±1.9 months (range 8-12 months). After CyA therapy the mean 24 hr urinary protein excretion declined from 107.1±35.1 mg/m2/hr to 7.4±2.4 mg/m2/hr (P<0.001) and serum albumin increased from 3.3±0.6 g/dL to 4.3±0.3 g/dL (P<0.001). At a follow-up biopsy the histological grade of IgAN was improved in seven (50%) of the 14 patients, remained the same in three (21%), and was aggravated in four (29%). Serum creatinine, creatinine clearance, and blood pressure did not differ before and after CyA therapy. Two patients (14%) showed CyA-induced nephrotoxicity at the second biopsy. Our findings indicate that CyA therapy may be effective in reducing proteinuria and regressing renal pathology in a subset of children with IgAN.
PMCID: PMC2858831  PMID: 20436708
Glomerulonephritis, IGA; Cyclosporine; Heavy Proteinuria; Child
9.  Smoking and Rheumatoid Arthritis 
Rheumatoid arthritis (RA) is a chronic inflammatory disease caused by both genetic and environmental factors. Smoking has been implicated as one of the most important extrinsic risk factors for its development and severity. Recent developments have shed light on the pathophysiology of RA in smokers, including oxidative stress, inflammation, autoantibody formation and epigenetic changes. The association of smoking and the development of RA have been demonstrated through epidemiologic studies, as well as through in vivo and animal models of RA. With increased use of biological agents in addition to standard disease-modifying antirheumatic drugs (DMARDs), there has been interest in how smoking affects drug response in RA treatment. Recent evidence suggests the response and drug survival in people treated with anti-tumour necrosis factor (anti-TNF) therapy is poorer in heavy smokers, and possible immunological mechanisms for this effect are presented in the current paper.
PMCID: PMC4284707  PMID: 25479074
rheumatoid arthritis; smoking; cyclic citrullinated peptide; synovial fibroblasts; drug response
10.  A case of thyrotoxic periodic paralysis as initial manifestation of Graves' disease in a 16-year-old Korean adolescent 
Thyrotoxic periodic paralysis (TPP) is a rare complication of hyperthyroidism, with recurrent muscle paralysis and hypokalemia that are caused by an intracellular shift of potassium. TPP is relatively common in Asian males, but is extremely rare in children and adolescents, even for those of Asian descent. We describe a 16-year-old Korean adolescent presenting with a two-week history of episodic leg weakness in the morning. He showed sinus tachycardia, lower leg weakness, and hypokalemia. Thyroid function test showed hyperthyroidism, and thyroid ultrasonography revealed a diffuse enlarged thyroid with increased vascularity, consistent with Graves' disease. He was treated with β-adrenergic blocker and antithyroid drugs. He has been symptom free for one year, as his hyperthyroidism has been controlled well with antithyroid drugs. TPP should be considered in children and adolescents with acute paralysis of the lower extremities and hypokalemia.
PMCID: PMC4208265  PMID: 25346923
Thyrotoxic periodic paralysis; Graves' disease; Adolescent; Korean
11.  Renovascular Hypertension Treated by Renal Artery Embolization 
Yonsei Medical Journal  2013;55(1):273-275.
Renovascular hypertension is caused by narrowing of the arteries supplying the kidneys. There are several methods to treat renal artery stenosis, such as medications, percutaneous transluminal renal angioplasty, and atherosclerosis. A boy presented to our hospital with severe hypertension. Computed tomography angiogram revealed severe narrowing of the left renal artery and hypoplastic left kidney. Total renal artery embolizaton was performed to make a complete occlusion of the left renal artery. Follow-up renin and aldosterone levels were gradually decreased. The main advantage of renal artery embolization is that it is minimally invasive compared with extensive surgical procedures. Therefore, renal artery embolization should be considered as an alternative to surgical nephrectomy in pediatric patients with renovascular hypertension.
PMCID: PMC3874892  PMID: 24339318
Renovascular hypertension; renal artery embolization; children
12.  Spot Urine Albumin to Creatinine Ratio and Serum Cystatin C are Effective for Detection of Diabetic Nephropathy in Childhood Diabetic Patients 
Journal of Korean Medical Science  2012;27(7):784-787.
Spot urinary albumin to creatinine ratio (ACR) measurement has been suggested as a surrogate to 24-hr urine collection for the assessment of microalbuminuria, and cystatin C (cysC) is known as an advantageous marker for renal function. The aim of this study was to evaluate the clinical values of spot urinary ACR and serum cysC for the assessment of diabetic nephropathy instead of 24-hr urine microalbumin in children and adolescents with diabetes. A total of 113 children and adolescents (age 12-19 yr, M:F = 47:66) with type 1 or 2 diabetes were enrolled. We evaluated the validity of spot urine ACR and serum cysC, and then compared them to 24-hr urine microalbumin and creatinine clearance. Spot urine ACR was correlated with 24-hr urine albumin excretion (R2 = 0.828, P = 0.001) and creatinine clearance (R2 = 0.249, P = 0.017). The ROC curve analysis of serum cysC demonstrated higher diagnostic accuracy than that of serum creatinine (AUC 0.732 vs 0.615). Both the measurements of spot urine ACR and serum cysC might better predict the presence of diabetic nephropathy than 24-hr urine microalbumin in childhood diabetic patients.
PMCID: PMC3390728  PMID: 22787375
Diabetic Nephropathies; Albumin to Creatinine Ratio; Cystatin C; Childhood Diabetes
13.  Urinary bladder rupture during voiding cystourethrography 
Korean Journal of Pediatrics  2012;55(5):181-184.
Voiding cystourethrography (VCUG) is a commonly performed diagnostic procedure for the evaluation of vesicoureteral reflux with urinary tract infection or congenital renal diseases in children. The procedure is relatively simple and cost-effective, and complications are very rare. The iatrogenic complication of VCUG range from discomfort, urinary tract infection to bacteremia, as well as bladder rupture. Bladder rupture is a rare complication of VCUG, and only a few cases were reported. Bladder rupture among healthy children during VCUG is an especially uncommon event. Bladder rupture associated with VCUG is usually more common in chronically unused bladders like chronic renal failure. Presented is a case of bladder rupture that occurred during a VCUG in a healthy 9-month-old infant, due to instilled action of dye by high pressure. This injury completely healed after 7 days of operation, and it was confirmed with a postoperative cystography. The patient's bladder volume, underlying disease, velocity of the contrast media instilled, catheter size, and styles of instillation are important factors to prevent bladder rupture during VCUG. Management of bladder rupture should be individualized, but the majority of infants are treated with the operation. In conclusion, bladder rupture is a rare complication, however, delicate attention is needed in order to prevent more dire situations.
PMCID: PMC3362733  PMID: 22670154
Urinary bladder; Rupture; Radiography
14.  The First Case of Familial Mediterranean Fever Associated with Renal Amyloidosis in Korea 
Yonsei Medical Journal  2012;53(2):454-458.
Familial Mediterranean fever (FMF) is an auto-inflammatory disease characterized by periodic episodes of fever and recurrent polyserositis. It is caused by a dysfunction of pyrin (or marenostrin) as a result of a mutation within the MEFV gene. It occurs mostly in individuals of Mediterranean origin; however, it has also been reported in non-Mediterranean populations. In this report, we describe the first case of FMF in a Korean child. As eight-year-old boy presented recurrent febrile attacks from an unknown cause, an acute scrotum and renal amyloidosis. He also showed splenomegaly, lymphadenopathy, pleural effusion, ascites and elevated acute phase reactants. After MEFV gene analysis, he was diagnosed as FMF combined with amyloidosis.
PMCID: PMC3282977  PMID: 22318840
Familial Mediterranean fever; amyloidosis; marenostrin
15.  Fulminant and Fatal Multiple Organ Failure in a 12-Year-Old Boy With Mycoplasma pneumoniae Infection 
Mycoplasma pneumoniae (Mp) is a unique pathogen that causes not only pulmonary but also extrapulmonary manifestations that must be rapidly diagnosed. A 12-year-old boy, with no relevant medical history, presented with fever, severe epigastric pain, and vomiting. Laboratory findings showed fulminant and cholestatic hepatitis, hemolytic anemia, thrombocytopenia, acute kidney injury, disseminated intravascular coagulopathy, acute myocardial infarction, and rhabdomyolysis. His clinical condition rapidly deteriorated during intubation and continuous renal replacement therapy. Despite intensive treatment, he did not recover. We report a case of fulminant and fatal multiple organ failure in a previously healthy boy with Mp infection, describing the possible pathomechanisms of multiple organ failure involved in the disease.
PMCID: PMC3242064  PMID: 22211173
Mycoplasma pneumoniae; multiple organ failure; rhabdomyolysis
16.  Renal Stone Associated with the Ketogenic Diet in a 5-Year Old Girl with Intractable Epilepsy 
Yonsei Medical Journal  2010;51(3):457-459.
In this paper, we report on a 5-year-old girl who developed a renal stone while following the ketogenic diet to treat refractory seizure disorder. Three months after initiating the ketogenic diet, she developed severe abdominal pain and vomiting. The spot urine calcium-to-creatinine (Ca/Cr) ratio and 24-hour urine evaluation showed hypercalciuria. Computed tomography (CT) imaging revealed a stone in the right ureteropelvic junction, resulting in hydronephrosis of the right kidney. The renal stone disappeared 5 days after conservative treatment; the patien's microscopic hematuria resolved concurrently. In light of this case report, we recommend regularly monitoring the urine Ca/Cr ratio with ultrasonography for further development of renal stones in patients following the ketogenic diet. If these patients exhibit evidence of symptomatic hypercalciuria or cyristalluria, liberalization of fluid restriction and urine alkalization using oral potassium citrate should be considered.
PMCID: PMC2852806  PMID: 20376903
Renal stone; ketogenic diet; epilepsy
17.  False Positive Immunoglobulin M Antibody to Cytomegalovirus in Child with Infectious Mononucleosis Caused by Epstein-Barr Virus Infection 
Yonsei Medical Journal  2009;50(5):713-716.
A 16-month-old boy was admitted because of cough that had lasted for 10 days. The patient showed severe hepatomegaly incidentally, and dual positivity of Immunoglobulin (Ig) M to Epstein-Barr virus (EBV) viral capsid antigen (VCA) and cytomegalovirus (CMV). On the basis of seroconversion to Epstein-Barr nuclear antigen (EBNA) Ig G positivity and reduced CMV Ig M titer with persistently negative CMV Ig G, a definite diagnosis of EBV-induced infectious mononucleosis was established 1 year 2 month later.
PMCID: PMC2768249  PMID: 19881978
Hepatomegaly; Epstein-Barr virus; cytomegalovirus
18.  Coinfection of Viral Agents in Korean Children with Acute Watery Diarrhea 
Journal of Korean Medical Science  2008;23(6):937-940.
Currently, there are a few reports on viral coinfection that causes an acute watery diarrhea in Korean children. So, to evaluate the features of coinfectious viral agents in children with acute watery diarrhea, we enrolled 155 children with acute watery diarrhea from July 2005 to June 2006. Fecal samples were collected and evaluated for various viral infections such as rotavirus, norovirus, adenovirus and astrovirus. The mean (±standard deviation) age of the children was 2.71±2.37 yr. The detection rate of viral agents was most common in children between the ages of 1 and 3 yr. Rotavirus was detected in 63 children (41.3%), norovirus in 56 (36.2%), adenovirus in 11 (7.1%), and astrovirus in 1 (0.6%). Regarding rotavirus, there were 38 (60.3%) cases with monoinfection and 25 (39.7%) with coinfection. For norovirus, there were 33 (58.9%) cases with monoinfection and 23 (41.1%) with coinfection. Coinfection with rotavirus and norovirus was most common, and occurred in 20/155 cases (12.9%) including coinfection with adenovirus. So, rotavirus and norovirus were the most common coinfectious viral agents in our study population with acute watery diarrhea.
PMCID: PMC2610655  PMID: 19119432
Coinfection; Watery Diarrhea; Rotavirus; Norovirus; Children
19.  Intravenous Cyclophosphamide Therapy in Adults with Henoch-Schönlein Purpura 
Clinics (Sao Paulo, Brazil)  2008;63(4):555-556.
PMCID: PMC2664137  PMID: 18719772
21.  Effect of renal Doppler ultrasound on the detection of nutcracker syndrome in children with hematuria 
European Journal of Pediatrics  2006;166(5):399-404.
To assess the detection rate of nutcracker syndrome in children with isolated hematuria, renal Doppler ultrasound examinations were routinely performed on 216 consecutive children (176 microscopic hematuria and 40 gross hematuria). Renal Doppler ultrasound was also performed on 32 healthy normal children. The peak velocity (PV) was measured at the hilar portion of the left renal vein (LRV) and at the LRV between the aorta and the superior mesenteric artery. The PV at the aortomesenteric portion (P=0.003) and the PV ratios of the LRV (P=0.003) were significantly higher in children with hematuria than in normal children, while the PV at the hilar portion was not different. If a PV ratio of the LRV of at least 4.1 (the cut-off level set at the mean ±2 SD of the value for the normal children) was defined as abnormal, 72 cases (33.3%) in children with hematuria and no cases in normal children were diagnosed as having nutcracker syndrome. The prevalence of nutcracker syndrome is relatively high in children with isolated hematuria, and the inclusion of renal Doppler ultrasound as a screening examination has a substantial effect on the detection of nutcracker syndrome.
PMCID: PMC1829442  PMID: 17051355
Nutcracker syndrome; Hematuria; Renal Doppler ultrasound; Screening examination

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