Tubulopathy: the clinical and genetic approach in diagnosis

Remarkable advances in genetic diagnosis expanded our knowledge about inherited tubulopathies and other genetic kidney diseases. This review suggests a simple categorization of inherited tubular disease, clarifies the concept of autosomal dominant tubulointerstitial kidney disease (ADTKD), and introduces novel therapies developed for tubulopathies. Facing patients with suspicious tubular disorders, clinicians should first evaluate the status of volume and acid-base. This step helps the clinicians to localize the affected segment and to confirm genetic diagnosis. ADTKD is a recently characterized disease entity involving tubules. The known causative genes are UMOD, MUC1, REN, and HNF1β. Still, only half of ADTKD patients show mutations for these four identified genes. Whole exome sequencing is a suitable diagnostic tool for tubulopathies, especially for ADTKD. Genetic approaches to treat tubulopathies have progressed recently. Despite the practical obstacles, novel therapies targeting inherited tubulopathies are currently in development.

Diverse renal manifestations of Alagille syndrome in Korean children

Purpose@#To determine the prevalence, clinical manifestations, and outcomes of renal involvements in pediatric Alagille syndrome (ALGS). @*Methods@#A total of 21 patients diagnosed with ALGS at age under 18 years who visited Samsung Medical Center from March 1999 to March 2022 were enrolled. ALGS was diagnosed either by clinical manifestations, targeted JAG1 sequencing, and/or liver biopsy. Medical records including sex, age, renal manifestations, urinalysis, serum creatinine, JAG1 sequencing, and ultrasonography were retrospectively reviewed. @*Results@#The male to female ratio was 9:12. The mean age of patients at confirmative diagnosis of ALGS was 18.4 months. Sanger sequencing was performed for 17 patients. Sixteen of 21 patients (76.1%) showed JAG1 mutations. Renal involvement was found in 10 patients (47.6%). The most common type of anomaly was renal dysplasia (40%). One patient having renal dysplasia was pathologically confirmed with glomerular lipid deposition. Two patients (20%) manifested nephrocalcinosisephrolithiasis. Among eight renal-involved patients who survived, four (50%) progressed to chronic kidney disease stage 3. Two of these chronic kidney disease patients were diagnosed with hepatorenal syndrome. The other four patients had renal functions preserved, including two without any interventions and two who underwent urological interventions. @*Conclusions@#The current study revealed a high prevalence of renal involvement in Korean pediatric ALGS with diverse phenotypes.

Intellectual Functioning of Pediatric Patients with Chronic Kidney Disease:Results from the KNOW-Ped CKD

Background@#Chronic kidney disease (CKD) has a negative impact on growth and development in children and is a risk factor for neurocognitive impairment; however, there is limited research on the cognitive function of children and adolescents with CKD. This study therefore aimed to investigate the mean intelligence and risk factors for low intelligence in children and adolescents with CKD. @*Methods@#Eighty-one patients with CKD under 18 years old were included in the KoreaN cohort study for Outcomes in patients With Pediatric Chronic Kidney Disease (KNOW-Ped CKD). Participants completed either the Wechsler Intelligence Scale for Children (6–16 years), or Wechsler Adult Intelligence Scale (> 16 years). @*Results@#The mean full-scale intelligence quotient (IQ) was 91 ± 19; 24.7% of participants scored a full-scale IQ below 80. Participants with a short stature (height Z scores < −1.88), failure to thrive (weight Z scores < −1.65), more severe CKD stage (≥ IIIb), longer duration of CKD (≥ 5 years), and those who were Medicare or Medicaid beneficiaries, had significantly lower mean full-scale IQs. @*Conclusion@#On linear regression analysis, the association between the full-scale IQ, and longer duration of CKD and growth failure, remained significant after controlling for demographic and clinical variables. It is therefore necessary to investigate cognitive impairment in pediatric patients with CKD who exhibit growth failure or for a longer postmorbid period. It is believed that early interventions, such as kidney transplantation, will have a positive effect on IQ in children with CKD, as the disease negatively affects IQ due to poor glomerular filtration rate over time.

Intellectual Functioning of Pediatric Patients with Chronic Kidney Disease:Results from the KNOW-Ped CKD

Background@#Chronic kidney disease (CKD) has a negative impact on growth and development in children and is a risk factor for neurocognitive impairment; however, there is limited research on the cognitive function of children and adolescents with CKD. This study therefore aimed to investigate the mean intelligence and risk factors for low intelligence in children and adolescents with CKD. @*Methods@#Eighty-one patients with CKD under 18 years old were included in the KoreaN cohort study for Outcomes in patients With Pediatric Chronic Kidney Disease (KNOW-Ped CKD). Participants completed either the Wechsler Intelligence Scale for Children (6–16 years), or Wechsler Adult Intelligence Scale (> 16 years). @*Results@#The mean full-scale intelligence quotient (IQ) was 91 ± 19; 24.7% of participants scored a full-scale IQ below 80. Participants with a short stature (height Z scores < −1.88), failure to thrive (weight Z scores < −1.65), more severe CKD stage (≥ IIIb), longer duration of CKD (≥ 5 years), and those who were Medicare or Medicaid beneficiaries, had significantly lower mean full-scale IQs. @*Conclusion@#On linear regression analysis, the association between the full-scale IQ, and longer duration of CKD and growth failure, remained significant after controlling for demographic and clinical variables. It is therefore necessary to investigate cognitive impairment in pediatric patients with CKD who exhibit growth failure or for a longer postmorbid period. It is believed that early interventions, such as kidney transplantation, will have a positive effect on IQ in children with CKD, as the disease negatively affects IQ due to poor glomerular filtration rate over time.

Characteristics of pediatric rhabdomyolysis and the associated risk factors for acute kidney injury: a retrospective multicenter study in Korea

Background@#The clinical features of pediatric rhabdomyolysis differ from those of the adults with rhabdomyolysis; however, multicenter studies are lacking. This study aimed to investigate the characteristics of pediatric rhabdomyolysis and reveal the risk factors for acute kidney injury (AKI) in such cases. @*Methods@#This retrospective study analyzed the medical records of children and adolescents diagnosed with rhabdomyolysis at 23 hospitals in South Korea between January 2007 and December 2016. @*Results@#Among 880 patients, those aged 3 to 5 years old composed the largest subgroup (19.4%), and all age subgroups were predominantly male. The incidence of AKI was 11.3%. Neurological disorders (53%) and infection (44%) were the most common underlying disorder and cause of rhabdomyolysis, respectively. The median age at diagnosis in the AKI subgroup was older than that in the non-AKI subgroup (12.2 years vs. 8.0 years). There were no significant differences in body mass index, myalgia, dark-colored urine, or the number of causal factors between the two AKI-status subgroups. The multivariate logistic regression model indicated that the following factors were independently associated with AKI: multiorgan failure, presence of an underlying disorder, strong positive urine occult blood, increased aspartate aminotransferase and uric acid levels, and reduced calcium levels. @*Conclusions@#Our study revealed characteristic clinical and laboratory features of rhabdomyolysis in a Korean pediatric population and highlighted the risk factors for AKI in these cases. Our findings will contribute to a greater understanding of pediatric rhabdomyolysis and may enable early intervention against rhabdomyolysis-induced AKI.

Consensus regarding diagnosis and management of atypical hemolytic uremic syndrome

Thrombotic microangiopathy (TMA) is defined by specific clinical characteristics, including microangiopathic hemolytic anemia, thrombocytopenia, and pathologic evidence of endothelial cell damage, as well as the resulting ischemic end-organ injuries. A variety of clinical scenarios have features of TMA, including infection, pregnancy, malignancy, autoimmune disease, and medications. These overlapping manifestations hamper differential diagnosis of the underlying pathogenesis, despite recent advances in understanding the mechanisms of several types of TMA syndrome. Atypical hemolytic uremic syndrome (aHUS) is caused by a genetic or acquired defect in regulation of the alternative complement pathway. It is important to consider the possibility of aHUS in all patients who exhibit TMA with triggering conditions because of the incomplete genetic penetrance of aHUS. Therapeutic strategies for aHUS are based on functional restoration of the complement system. Eculizumab, a monoclonal antibody against the terminal complement component 5 inhibitor, yields good outcomes that include prevention of organ damage and premature death. However, there remain unresolved challenges in terms of treatment duration, cost, and infectious complications. A consensus regarding diagnosis and management of TMA syndrome would enhance understanding of the disease and enable treatment decision-making.

Therapeutic Drug Level Monitoring of Teicoplanin in Korean Pediatric Patients with Normal versus Impaired Renal Function

Background@#Teicoplanin is used to treat serious gram-positive infections. Optimal teicoplanin trough levels are considered to be ≥ 10 μg/mL. Despite its wide use in various clinical settings, data on teicoplanin trough level in pediatric patients are limited. Therefore, the aim of this study was to investigate the therapeutic drug level monitoring of teicoplanin in Korean pediatric patients, including those with impaired renal function. @*Methods@#A retrospective study was performed in pediatric patients (age ≤ 18 years old) who received teicoplanin from September 2014 to April 2018. The regimen included a loading dose of 10 mg/kg/dose at 12 hours' interval three times in a row, and a maintenance dose of 10 mg/kg/dose commenced at 24 hours of interval after the loading dose, with a maximum of 400 mg/dose, respectively. The first therapeutic drug levels were measured. Distribution and characteristics of trough levels in patients with decreased renal function and those with bacteremia were also assessed. @*Results@#A total of 187 trough levels were collected from 143 patients. Hematologic and oncologic diseases were the most common underlying diseases (83.2%, n = 119). One hundred eighty trough levels were first measured, and their median value was 16.2 μg/mL (range, 2.3–100 μg/mL) and the median interval between initial teicoplanin injection and 1st trough level was 96.5 hours (range 47.6–179.3 hours). Lower steady-state levels were observed in younger age group (median, 13.5 vs. 18.0 μg/mL, P = 0.038). Median trough levels were higher in patients with decreased renal functions (P < 0.001). In addition, among eight with gram-positive bacteremia, seven of them had a favorable outcome. @*Conclusion@#This study provides additive information on trough level monitoring of teicoplanin in children with impaired renal function and treatment effect in patients with gram-positive bacteremia. Careful monitoring for steady state trough levels of teicoplanin is warranted.

Pediatric Hemodialysis

Hemodialysis is rarely used in neonates and infants due to the risk of major complications in the very young. Nevertheless, there are clinical situations where hemodialysis is needed and may be helpful in small children. Recently, new developments in specialized hemodialysis equipment and specifically trained personnel have made it possible to implement hemodialysis in neonates and infants. In this review, we will discuss hemodialysis for the treatment of small children with renal replacement therapy-requiring conditions, and consider indications, prescriptions, complications, and ethical issues.

Effect of Hypertension on Childhood-onset Systemic Lupus Erythematous in a Tertiary Medical Center in Korea

Purpose@#The purpose of this study was to evaluate the prevalence, clinical characteristics, and long-term clinical effects of hypertension in Korean childhood-onset systemic lupus erythematous (SLE) patients. @*Methods@#The medical records of SLE patients, diagnosed by 2019 SLE European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) classification criteria, who visited Samsung Medical Center from January 2009 to May 2019 were reviewed. Disease activity and long-term damage were evaluated using the Modified Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) and the Pediatric Systemic Lupus International Collaborating Clinics/ACR Damage Index (Ped-SDI), respectively. The sex-, age- and height-blood pressure standards recommended by the American Academy of Pediatrics 2017 guideline was used to define hypertension. @*Results@#A total of 32 patients were enrolled in this study. The median follow-up duration was 7.3 years and females were predominant. The median ages at SLE and hypertension diagnoses were 14.2 and 14.3 years, respectively. The biopsyproven lupus nephritis was detected in 90.6% and 37.5% were class IV. During the follow-up, 12 patients (37.5%) had hypertension. Among them, 2 patients had 3 episodes of posterior reversible encephalopathy syndrome and 5 patients had left ventricular hypertrophy (LVH). Univariate analysis showed baseline hypertension was significantly correlated with a lower estimated glomerular filtration rate, higher body mass index and SLEDAI at baseline. The development of hypertension during the follow-up was significantly correlated with obesity, LVH, and higher Ped-SDI. @*Conclusion@#Our study revealed that hypertension in pediatric SLE is associated with obesity and renal function at SLE diagnosis and could affect long-term damage.

Clinical manifestations of BK virus infection in pediatric kidney transplant patients / 소아과

BACKGROUND: Polyomavirus BK (BKV) infection is an important cause of graft loss in kidney transplant patients.PURPOSE: The purpose of this study was to evaluate clinical findings and risk factors for BKV in pediatric patients after kidney transplantation.METHODS: This retrospective single-center study included 31 pediatric kidney transplant recipients from January 2002 to December 2017. Two patients received 2 transplantations during the study period, and each transplant was analyzed independently. Total number of cases is 33 cases with 31 patients. BKV infection was confirmed from blood samples via periodic quantitative polymerase chain reaction.RESULTS: The mean age at kidney transplantation was 11.0±4.7 years, and the male-to-female ratio was 2.7:1. Three patients had a past medical history of high-dose chemotherapy and autologous stem-cell transplantation for solid tumors. Nine patients (27.3%) developed BKV infection. The median period from kidney transplantation to BKV detection in blood was 5.6 months. There was no statistically significant difference in estimated glomerular filtration rate between patients with and those without BKV infection. Among 9 patients with BKV viremia, 7 were treated by reducing their immunosuppressant dose, and BKV was cleared in 6 of these 7 patients. In the other 2 BKV-positive patients, viremia improved without immunosuppressant reduction.CONCLUSION: BKV infection is common in children with kidney transplantation and might not have affected short-term renal function in our patient sample due to early immunosuppressant reduction at the time of BKV detection.

Renal replacement therapy in neonates with an inborn error of metabolism / 소아과

Hyperammonemia can be caused by several genetic inborn errors of metabolism including urea cycle defects, organic acidemias, fatty acid oxidation defects, and certain disorders of amino acid metabolism. High levels of ammonia are extremely neurotoxic, leading to astrocyte swelling, brain edema, coma, severe disability, and even death. Thus, emergency treatment for hyperammonemia must be initiated before a precise diagnosis is established. In neonates with hyperammonemia caused by an inborn error of metabolism, a few studies have suggested that peritoneal dialysis, intermittent hemodialysis, and continuous renal replacement therapy (RRT) are effective modalities for decreasing the plasma level of ammonia. In this review, we discuss the current literature related to the use of RRT for treating neonates with hyperammonemia caused by an inborn error of metabolism, including optimal prescriptions, prognosis, and outcomes. We also review the literature on new technologies and instrumentation for RRT in neonates

Acute kidney injury in pediatric patients with rhabdomyolysis / 소아과

PURPOSE: This study aimed to evaluate the clinical findings in pediatric rhabdomyolysis and the predictive factors for acute kidney injury (AKI) in Korean children. METHODS: Medical records of 39 Korean children, who were newly diagnosed with rhabdomyolysis from January 2008 to December 2015, were retrospectively analyzed. The diagnosis was made from the medical history, elevated serum creatinine kinase level >1,000 IU/L, and plasma myoglobin level >150 ng/mL. Patients with muscular dystrophy and myocardial infarction were excluded. RESULTS: The median patient age at diagnosis was 14.0 years (range, 3–18 years), and the male to female ratio was 2.5. The most common presenting symptom was myalgia (n=25, 64.1%), and 14 patients (35.9%) had rhabdomyolysis-induced AKI. Eighteen patients (46.2%) had underlying diseases, such as epilepsy and psychotic disorders. Ten of these patients showed rhabdomyolysis-induced AKI. The common causes of rhabdomyolysis were infection (n=12, 30.7%), exercise (n=9, 23.1%), and trauma (n=8, 20.5%). There was no difference in the distribution of etiology between AKI and non-AKI groups. Five patients in the AKI group showed complete recovery of renal function after stopping renal replacement therapy. The median length of hospitalization was 7.0 days, and no mortality was reported. Compared with the non-AKI group, the AKI group showed higher levels of peak creatinine kinase and myoglobin, without statistical significance. CONCLUSION: The clinical characteristics of pediatric rhabdomyolysis differ from those observed in adult patients. Children with underlying diseases are more vulnerable to rhabdomyolysis-induced AKI. AKI more likely develops in the presence of a high degree of albuminuria.

Publication of the Korea-WHO Cooperation History — 70 Years of Working Together for Heath: World Health Organization and the Republic of Korea

The World Health Organization (WHO) have been in collaborative efforts with the Republic of Korea in keeping of and for better health for all for the past decades. From the control of parasites to building of community health system in rural places, the works has now resulted in healthier Korea than ever, and has transformed the role of engaging as the world leader in contribution of health and development. Seventy years of independence, war, and poverty, transforming from a recipient country of official development assistance to a significant donor to the global society, we have emphasized the importance of international cooperation and the role of WHO in the past years in Korea and neighboring countries. Looking back of the past is meaningful to diagnose the present problems, and to foresee the future of our world.

Posterior reversible encephalopathy syndrome caused by presumed Takayasu arteritis / 소아과

Takayasu arteritis (TA) is a chronic inflammatory disease of unknown etiology that affects mainly the aorta, main aortic branches, and pulmonary arteries. Diverse neurological manifestations of TA have rarely been reported in children. Posterior reversible encephalopathy syndrome (PRES) is a neuroradiological condition that presents with headache, seizure, visual disturbances, and characteristic lesions on imaging. Inflammatory condition and severe hypertension in TA can cause PRES. We report of a 5-year-old girl with presumed TA who presented with PRES and chronic total occlusion in the renal artery. The findings on magnetic resonance imaging suggested PRES. Left nephrectomy was performed for total occlusion of the left renal artery, and the confirmatory diagnosis of TA was based on the pathologic findings of the renal artery.

A novel mutation of CLCNKB in a Korean patient of mixed phenotype of Bartter-Gitelman syndrome / 소아과

Bartter syndrome (BS) is an inherited renal tubular disorder characterized by low or normal blood pressure, hypokalemic metabolic alkalosis, and hyperreninemic hyperaldosteronism. Type III BS is caused by loss-of-function mutations in CLCNKB encoding basolateral ClC-Kb. The clinical phenotype of patients with CLCNKB mutations has been known to be highly variable, and cases that are difficult to categorize as type III BS or other hereditary tubulopathies, such as Gitelman syndrome, have been rarely reported. We report a case of a 10-year-old Korean boy with atypical clinical findings caused by a novel CLCNKB mutation. The boy showed intermittent muscle cramps with laboratory findings of hypokalemia, severe hypomagnesemia, and nephrocalcinosis. These findings were not fully compatible with those observed in cases of BS or Gitelman syndrome. The CLCNKB mutation analysis revealed a heterozygous c.139G>A transition in exon 13 [p.Gly(GGG)465Glu(GAG)]. This change is not a known mutation; however, the clinical findings and in silico prediction results indicated that it is the underlying cause of his presentation.

Clinical Practice Guidelines for the Management of Atypical Hemolytic Uremic Syndrome in Korea

Atypical hemolytic uremic syndrome (aHUS) is a rare syndrome characterized by micro-angiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury. The major pathogenesis of aHUS involves dysregulation of the complement system. Eculizumab, which blocks complement C5 activation, has recently been proven as an effective agent. Delayed diagnosis and treatment of aHUS can cause death or end-stage renal disease. Therefore, a diagnosis that differentiates aHUS from other forms of thrombotic microangiopathy is very important for appropriate management. These guidelines aim to offer recommendations for the diagnosis and treatment of patients with aHUS in Korea. The guidelines have largely been adopted from the current guidelines due to the lack of evidence concerning the Korean population.

Prevention of Pediatric Acute Kidney Injury

The incidence of acute kidney injury (AKI) in critically ill pediatric patients has been reported as increasing to 25 %, depending on population characteristics. The etiology of AKI has changed over the last 10-20 years from primary renal disease to the renal conditions associated with systemic illness. The AKI in pediatric population is associated with increased mortality and morbidity, and prevention is needed to reduce the consequence of AKI. It is known that the most important risk factors for AKI in critically ill pediatric patients are clinical conditions to be associated with decreased renal blood flow, direct renal injury, and illness severity. Renal hypoperfusion leads to neurohormonal activation including renin-angiotensinaldosterone system, sympathetic nervous system, antidiuretic hormone, and prostaglandins. Prolonged renal hypoperfusion can result in acute tubular necrosis. The direct renal injury can be predisposed under the condition of renal hypoperfusion, and appropriate treatment of volume depletion is important to prevent AKI. The preventable causes of AKI include contrast-induced nephropathy, hemodynamic instability, inappropriate mediation use, and multiple nephrotoxic insults. Given the evidence of preventable factors for AKI, several actions such as the use of protocol for prevention of contrast-induced nephropathy, appropriate treatment of volume depletion, vigorous treatment of sepsis, avoidance of combinations of nephrotoxic medications, and monitoring of levels of drugs should be recommended.

Burkholderia Cepacia Causing Nosocomial Urinary Tract Infection in Children

PURPOSE: Burkholderia cepacia is an aerobic, glucose-non-fermenting, gramnegative bacillus that mainly affects immunocompromised and hospitalized patients. Burkholderia cepacia has high levels of resistance to many antimicrobial agents, and therapeutic options are limited. The authors sought to analyze the incidence, clinical manifestation, risk factors, antimicrobial sensitivity and outcomes of B. cepacia urinary tract infection (UTI) in pediatric patients. METHODS: Pediatric patients with urine culture-proven B. cepacia UTI between January 2000 and December 2014 at Samsung Medical Center, a tertiary referral hospital in Seoul, Republic of Korea, were included in a retrospective analysis of medical records. RESULTS: Over 14 years, 14 patients (male-to-female ratio of 1:1) were diagnosed with B. cepacia UTI. Of 14 patients with UTI, 11 patients were admitted to the intensive care unit, and a bladder catheter was present in 9 patients when urine culture was positive for B. cepacia. Patients had multiple predisposing factors for UTI, including double-J catheter insertion (14.2%), vesico-ureteral reflux (28. 6%), congenital heart disease (28.6%), or malignancy (21.4%). Burkholderia cepacia isolates were sensitive to piperacillin-tazobactam and sulfamethoxazole-trimethoprim, and resistant to amikacin and colistin. Treatment with parenteral or oral antimicrobial agents including piperacillin-tazobactam, ceftazidime, meropenem, and sulfamethoxazole-trimethoprim resulted in complete recovery from UTI. CONCLUSION: Burkholderia cepacia may be a causative pathogen for nosocomial UTI in pediatric patients with predisposing factors, and appropriate selection of antimicrobial therapy is necessary because of high levels of resistance to empirical therapy, including aminoglycosides.

The Antibiotic Resistance Pattern of Gram-Negative Bacteria in Children Younger Than 24 Months with a Urinary Tract Infection: A Retrospective Single-Center Study over 15 Consecutive Years

PURPOSE: We investigated trends in antibiotic resistance for gram-negative bacteria in infants with a urinary tract infection (UTI) over 15 years at a single institution. METHODS: A retrospective chart review was conducted for children younger than 24 months who visited the emergency room and were diagnosed with a UTI between January 2000 and December 2014. We selected urine culture data that grew Escherichia coli and Klebsiella pneumoniae. Baseline clinical information and results of antimicrobial susceptibility tests were analyzed by dividing the 15-year study time frame into three periods (A: 2000-2004, B: 2005-2009, and C: 2010-2014). RESULTS: During the study period, 478 applicable children were identified (E. coli, 89.7% and K. pneumoniae, 10.3%). Antibiotic resistance to third-generation cephalosporins was increased from period A to period C (A, 2.1%; B, 8.3%; C, 8.8%; P=0.025). Resistance to quinolones also showed a steady pattern during periods A to C, although it was not statistically significant (A, 7.9%; B, 9.7%; C, 12.4%; P=0.221). The incidence of Extended-spectrum beta-lactamase (ESBL)-producing gram-negative bacteria increased from period A to period C (A, 1.4%; B, 7.6%; C, 8.2%; P=0.012). CONCLUSION: This study revealed that the common uropathogens E. coli and K. pneumoniae experienced increasing resistance rates against third-generation cephalosporins and a constant antibiotic resistance to quinolones in children younger than 24 months. We also showed a recent increased incidence of ESBL-producing gram-negative bacteria in patients with community-acquired UTIs. Therefore, it is necessary to actively surveil resistance in order to properly select empirical antibiotics.

Complement regulation: physiology and disease relevance / 소아과

The complement system is part of the innate immune response and as such defends against invading pathogens, removes immune complexes and damaged self-cells, aids organ regeneration, confers neuroprotection, and engages with the adaptive immune response via T and B cells. Complement activation can either benefit or harm the host organism; thus, the complement system must maintain a balance between activation on foreign or modified self surfaces and inhibition on intact host cells. Complement regulators are essential for maintaining this balance and are classified as soluble regulators, such as factor H, and membrane-bound regulators. Defective complement regulators can damage the host cell and result in the accumulation of immunological debris. Moreover, defective regulators are associated with several autoimmune diseases such as atypical hemolytic uremic syndrome, dense deposit disease, age-related macular degeneration, and systemic lupus erythematosus. Therefore, understanding the molecular mechanisms by which the complement system is regulated is important for the development of novel therapies for complement-associated diseases.