Stabilization of serum alkaline phosphatase in hemodialysis patients by implementation of local chronic kidney disease-mineral bone disorder management strategy: A quality improvement study

Jin, Kyubok,Ban, Tae Hyun,Jung, Ji Yong,Kim, Ae Jin,Kim, Yaerim,Lee, So-Young,Yang, Dong Ho,Choi, Bum Soon,Oh, Kook-Hwan,Kim, Jieun,Kwon, Young Joo,Choi, Jong Wook,Kim, Gheun-Ho Korean Society of Nephrology 2018 Kidney Research and Clinical Practice Vol.37 No.2

<P><B>Background</B></P><P>The aim of this study is to narrow the gap between global guidelines and local practices, we recently established domestic recommendations by adapting the international guidelines for management of chronic kidney disease-mineral bone disorder (CKD-MBD) in patients on maintenance hemodialysis (MHD). This study was undertaken to determine whether application of this guideline adaptation was associated with improved serum mineral profiles in patients with CKD-MBD.</P><P><B>Methods</B></P><P>A total of 355 patients on MHD were enrolled from seven dialysis units. After adhering to our strategy for one year, serum phosphorus, calcium, intact parathyroid hormone (iPTH), and alkaline phosphatase (AP) levels were compared with the baseline. The endpoint was improvement in the proportion of patients with serum mineral levels at target recommendations.</P><P><B>Results</B></P><P>The median serum phosphorus level and proportion of patients with serum phosphorus within the target range were not changed. Although the median serum calcium level was significantly increased, the proportion of patients with serum calcium within the target range was not significantly affected. The proportion of patients with serum iPTH at the target level was not altered, although the median serum iPTH was significantly decreased. However, both median serum AP and the proportion of patients with serum AP at the target level (70.4% vs. 89.6%, <I>P</I> < 0.001) were improved.</P><P><B>Conclusion</B></P><P>In our patients with MHD, serum mineral profiles were altered and the serum AP level stabilized after implementing our recommendations. Long-term follow-up evaluations are necessary to determine whether uremic bone disease and cardiovascular calcifications are affected by these recommendations.</P>

Timing for initiation of sequential continuous renal replacement therapy in patients on extracorporeal membrane oxygenation

Paek, Jin Hyuk,Park, Seohyun,Lee, Anna,Park, Seokwoo,Chin, Ho Jun,Na, Ki Young,Lee, Hajeong,Park, Jung Tak,Kim, Sejoong Korean Society of Nephrology 2018 Kidney Research and Clinical Practice Vol.37 No.3

<P><B>Background</B></P><P>Extracorporeal membrane oxygenation (ECMO) is a lifesaving therapy used in critically ill patients with severe cardiopulmonary dysfunction. Continuous renal replacement therapy (CRRT) is supplemented to treat fluid overload, acute kidney injury, and electrolyte disturbances during ECMO. However, the best time to initiate CRRT is not well-defined. We performed this study to identify the optimal timing of CRRT for ECMO.</P><P><B>Methods</B></P><P>We conducted a multicenter retrospective cohort study of 296 patients over 12 years. Patients received CRRT during ECMO at Seoul National University Hospital, Seoul National University Bundang Hospital, or Yonsei University Hospital. We assigned patients to an early or late CRRT group depending on the CRRT initiation time. We considered early CRRT to be CRRT instituted within 72 hours of ECMO initiation.</P><P><B>Results</B></P><P>Among 296 patients, 212 patients (71.6%) received early CRRT. After using a propensity score matching method, 47 patients were included in each group. The time from ECMO initiation to CRRT initiation was 1.1 ± 0.9 days in the early CRRT group and 14.6 ± 18.6 days in the late CRRT group. No difference in patients’ mortality (<I>P</I> = 0.834) or hospital stay (<I>P</I> = 0.627) between the early and late CRRT groups was found. After adjusting all covariables, there was no significant difference in mortality between the early and late CRRT groups (hazard ratio, 0.697; 95% confidence interval, 0.410–1.184; <I>P</I> = 0.182).</P><P><B>Conclusion</B></P><P>This study showed that early CRRT may not be superior to late CRRT in ECMO patients. Further clinical trials are warranted.</P>

Anti-phospholipase A2 receptor antibody as a prognostic marker in patients with primary membranous nephropathy

Song, Eun Joo,Jeong, Kye Hwa,Yang, Young Ae,Lim, Jeong-Hoon,Jung, Hee-Yeon,Choi, Ji-Young,Cho, Jang-Hee,Kim, Chan-Duck,Kim, Yong-Lim,Park, Sun-Hee Korean Society of Nephrology 2018 Kidney Research and Clinical Practice Vol.37 No.3

<P><B>Background</B></P><P>Phospholipase A2 receptor (PLA2R) has been identified as a major autoantigen in primary membranous nephropathy (MN). We evaluated the association between anti-PLA2R antibodies and clinical outcome in Korean patients with primary MN.</P><P><B>Methods</B></P><P>A total of 66 patients with biopsy-proven MN were included. Serum level of anti-PLA2R antibodies was measured by enzyme-linked immunosorbent assay. Biochemical parameters were estimated initially and at follow-up.</P><P><B>Results</B></P><P>Anti-PLA2R antibodies were detected in 52.1% and 27.8% of patients with primary and secondary MN, respectively. Forty-eight patients with primary MN were grouped based on presence or absence of anti-PLA2R antibodies. Proteinuria was more severe in anti-PLA2R-positive patients than in anti-PLA2R-negative patients (urine protein/creatinine ratio 7.922 ± 3.985 g/g vs. 4.318 ± 3.304 g/g, <I>P</I> = 0.001), and anti-PLA2R antibody level was positively correlated with proteinuria. The incidence of chronic kidney disease stage ≥ 3 was higher in anti-PLA2R-positive patients compared with anti-PLA2R-negative patients (<I>P</I> = 0.004). The probabilities of spontaneous remission were higher in anti-PLA2R-negative patients compared with anti-PLA2R-positive patients (<I>P</I> < 0.001). Multivariate analysis demonstrated that anti-PLA2R antibodies are an independent risk factor for developing chronic kidney disease stage ≥ 3 and for not reaching spontaneous remission.</P><P><B>Conclusion</B></P><P>Detection of anti-PLA2R antibodies at diagnosis in patients with primary MN can predict prognosis and guide treatment decisions.</P>

Clinical Manifestation Patterns and Trends in Poststreptococcal Glomerulonephritis

Kim, Kee Hyuck Korean Society of Pediatric Nephrology 2016 Childhood kidney diseases Vol.20 No.1

Poststreptococcal glomerulonephritis (PSGN) is one of the most recognized diseases in pediatric nephrology. Typical clinical features include rapid onset of gross hematuria, edema, and hypertension, and cases are typically preceded by an episode of group A ${\beta}$-hemolytic streptococcus pharyngitis or pyoderma. The most common presenting symptoms of PSGN are the classic triad of glomerulonephritis: gross hematuria, edema, and hypertension. However, patients with PSGN sometimes present with unusual or atypical clinical symptoms that often lead to delayed diagnosis or misdiagnosis of the disease and increased morbidity. Additionally, the epidemiology of postinfectious glomerulonephritis (PIGN), including PSGN, has changed over the past few decades. This paper reviews atypical clinical manifestations of PSGN and discusses the changing demographics of PIGN with a focus on PSGN.

Vitamin D Dependent Rickets Type 1A Caused by CYP27B1 Mutation

Bak, Na Ry,Song, Eun Song,Yang, Eun Mi,Kim, Chan Jong Korean Society of Pediatric Nephrology 2019 Childhood kidney diseases Vol.23 No.2

Vitamin D dependent rickets type 1A (VDDR1A) is an autosomal recessive disorder caused by mutations in CYP27B1. Clinical findings are growth retardation, hypotonia, muscle weakness, hypocalcemic seizures, and radiological features of rickets. We aimed to present the VDDR1A case with a genetic study of CYP27B1. The 14-month-old boy was admitted to the hospital due to a seizure. Serum calcium, phosphorus, alkaline phosphatase, parathyroid hormone (PTH), 25(OH) vitamin D, and 1,25(OH)2 vitamin D values were 5.1 mg/dL, 3.7 mg/dL, 705 IU/L, 429 pg/mL, 24.9 ng/mL, and 8.8 pg/mL, respectively. Radiological study showed cupping and fraying of the distal ulna and radius. The molecular genetic study revealed that the patient had a compound heterozygous mutation, $Phe443Profs^*24$ and c.589+1G>A, in CYP27B1. Genetic analysis of the family members presented that the mother was heterozygous for the mutation c.589+1G>A, and that the father was heterozygous for $Phe443Profs^*24$. The patient was treated with calcium lactate and calcitriol. Until now, six Korean patients with VDDR1A have been studied. Including this case, Korean patients with VDDR1A were found to have only three different mutations in 14 alleles, indicating that the mutation in the CYP27B1 gene is homogeneous in the Korean population.

Clinical Guideline for Childhood Urinary Tract Infection (Second Revision)

Lee, Seung Joo Korean Society of Pediatric Nephrology 2015 Childhood kidney diseases Vol.19 No.2

To revise the clinical guideline for childhood urinary tract infections (UTIs) of the Korean Society of Pediatric Nephrology (2007), the recently updated guidelines and new data were reviewed. The major revisions are as follows. In diagnosis, the criterion for a positive culture of the catheterized or suprapubic aspirated urine is reduced to 50,000 colony forming uits (CFUs)/mL from 100,000 CFU/mL. Diagnosis is more confirmatory if the urinalysis is abnormal. In treating febrile UTI and pyelonephritis, oral antibiotics is considered to be as effective as parenteral antibiotics. In urologic imaging studies, the traditional aggressive approach to find primary vesicoureteral reflux (VUR) and renal scar is shifted to the targeted restrictive approach. A voiding cystourethrography is not routinely recommended and is indicated only in atypical or complex clinical conditions, abnormal ultrasonography and recurrent UTIs. $^{99m}Tc$-DMSA renal scan is valuable in diagnosing pyelonephritis in children with negative culture or normal RBUS. Although it is not routinely recommended, normal scan can safely avoid VCUG. In prevention, a more natural approach is preferred. Antimicrobial prophylaxis is not supported any more even in children with VUR. Topical steroid (2-4 weeks) to non-retractile physiologic phimosis or labial adhesion is a reasonable first-line treatment. Urogenital hygiene is important and must be adequately performed. Breast milk, probiotics and cranberries are dietary factors to prevent UTIs. Voiding dysfunction and constipation should be properly treated and prevented by initiating toilet training at an appropriate age (18-24 months). The follow-up urine test on subsequent unexplained febrile illness is strongly recommended. Changes of this revision is not exclusive and appropriate variation still may be accepted.

Novel SLC5A2 Mutations and Genetic Characterization in Korean Patients with Familial Renal Glucosuria

Lee, Weon Kyung,Oh, Seung Hwan,Chung, Woo Yeong Korean Society of Pediatric Nephrology 2018 Childhood kidney diseases Vol.22 No.2

Purpose: Familial renal glucosuria (FRG, OMIM #233100) is a rare but relatively benign genetic condition characterized by persistent isolated glucosuria with a normal blood glucose level. We report three additional SLC5A2 mutations and examine their phenotypic and genetic characteristics in a Korean FRG cohort. We also reviewed the literature and summarized the genotypes of all Korean patients with FRG. Methods: A genetic analysis was conducted by directly sequencing all 14 exons of the SLC5A2 gene and their flanking regions in six unrelated Korean children with FRG and their family members. Novel non-synonymous single-nucleotide polymorphisms were identified and compared with known mutations that are repeatedly detected in the Korean population. Results: We found two novel mutations [c.274G>A (G92S) and c.1168C>T (L390F)] and one known [c.1382G>A (S461N)] mutation in each family and one recurrent mutation [c.1346G>A (G449D) (rs768392222)] in two pedigrees. The recurrent G449D was predicted to be "possibly damaging," with a score of 0.883 in Polyphen-2, while G92S, L390F, and S461N were predicted to be "probably damaging," with scores of 1.000, 0.999, and 0.996, respectively. Conclusions: Two novel, one previously reported, and one recurrent mutation were identified in six Korean FRG pedigrees as causative mutations of renal glucosuria. Sequence variations in the SLC5A2 gene were frequently detected in children with persistent isolated glucosuria. A long-term follow-up of this FRG cohort is needed to understand how these specific SGLT2 mutations impair kidney function and energy homeostasis.

Genetic Basis of Steroid Resistant Nephrotic Syndrome

Park, Eujin Korean Society of Pediatric Nephrology 2019 Childhood kidney diseases Vol.23 No.2

Steroid-resistant nephrotic syndrome (SRNS) has long been a challenge for clinicians due to its poor responsiveness to immunosuppressants, and rapid progression to end-stage renal disease. Identifying a monogenic cause for SRNS may lead to a better understanding of podocyte structure and function in the glomerular filtration barrier. This review focuses on genes associated with slit diaphragm, actin cytoskeleton, transcription factors, nucleus, glomerular basement membrane, mitochondria, and other proteins that affect podocyte biology.

Effects of Rituximab Including Long-term Maintenance Therapy in Children with Nephrotic Syndrome in a Single Center of Korea

Kim, Seong Heon,Lim, Taek Jin,Song, Ji Yeon,Kim, Su Young Korean Society of Pediatric Nephrology 2018 Childhood kidney diseases Vol.22 No.1

Rituximab (RTX) is a chimeric monoclonal antibody that inhibits CD20-mediated B-cell proliferation and differentiation. Several studies have examined its use in intractable nephrotic syndrome (NS) with some positive results. However, those studies examined such effects for a short-term period of 1 year, and some patients continued to relapse after a lapse in RTX treatment. Our use of RTX as a maintenance therapy (RTX injection when the CD19 cell count exceeded $100-200/{\mu}L$ before relapse) showed some noticeable efficacy. We used RTX in 19 patients with steroid-dependent NS (SDNS). In 12 patients treated with RTX maintenance therapy, only one relapse occurred. The mean treatment period was $23.4{\pm}12.7months$, and the mean number of RTX administrations was $3.9{\pm}1.6$. The relapse rates were decreased (from 2.68/year to 0.04/year), and the drug-free period also increased (from 22.5 days/year to 357.1 days/year) during maintenance therapy. The other seven patients were treated with one cycle of RTX or additional cycles in case of relapse (non-maintenance therapy). Relapse rates were significantly decreased after RTX treatment (from 1.76/year to 0.96/year, P=0.017). The relapse-free period was $15.55{\pm}7.38$ (range, 5.3-30.7) months. No severe side effects of RTX were found except for a hypersensitivity reaction such as fever and chills during its infusion. In conclusion, RTX is considered an effective and safe option to reduce the relapse rate by a single- or maintenance-interval therapy in SDNS.

Cell-derived Secretome for the Treatment of Renal Disease

Kim, Michael W.,Ko, In Kap,Atala, Anthony,Yoo, James J. Korean Society of Pediatric Nephrology 2019 Childhood kidney diseases Vol.23 No.2

Kidney disease is a major global health issue. Hemodialysis and kidney transplantation have been used in the clinic to treat renal failure. However, the dialysis is not an effective long-term option, as it is unable to replace complete renal functions. Kidney transplantation is the only permanent treatment for end-stage renal disease (ESRD), but a shortage of implantable kidney tissues limits the therapeutic availability. As such, there is a dire need to come up with a solution that provides renal functions as an alternative to the current standards. Recent advances in cell-based therapy have offered new therapeutic options for the treatment of damaged kidney tissues. Particularly, cell secretome therapy utilizing bioactive compounds released from therapeutic cells holds significant beneficial effects on the kidneys. This review will describe the reno-therapeutic effects of secretome components derived from various types of cells and discuss the development of efficient delivery methods to improve the therapeutic outcomes.