OBJECTIVE: To explore the clinical characteristics and genetic etiology for a child with atypical Hemolytic uremic syndrome (aHUS) in conjunct with nephrotic level proteinuria. METHODS: A child patient who had visited the Affiliated Hospital of Qingdao University on June 25, 2020 was selected as the study subject. Clinical data of the patient was collected. Whole exome sequencing (WES) was carried out for the child, and candidate variant was verified by Sanger sequencing of the child and his parents. RESULTS: The child, an 8-month-old male, had presented mainly with edema, oliguria, hematuria, nephrotic level proteinuria, anemia, thrombocytopenia, increased creatinine and urea, hypercholesterolemia but normal complement levels. Genetic testing revealed that he has harbored compound heterozygous variants of the DGKE gene, namely c.12_18dupGAGGCGG (p.P7fs*37) and c.1042G>T (p.D348Y), which were respectively inherited from his father and mother. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variants were classified as likely pathogenic and variant of uncertain significance, respectively. By combining his clinical manifestations and results of genetic testing, the child was diagnosed with aHUS with nephrotic level proteinuria. CONCLUSION For infants and young children with aHUS in conjunct with nephrotic level proteinuria, variants of the DGKE gene should be screened. Above finding has expanded the mutational spectrum of the DGKE gene.
Infant ; Female ; Humans ; Child ; Male ; Child, Preschool ; Atypical Hemolytic Uremic Syndrome/diagnosis* ; Mutation ; Genetic Testing ; Thrombocytopenia/genetics* ; Proteinuria/genetics*

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.
Adolescent ; Adult ; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis ; Antibodies, Antineutrophil Cytoplasmic ; Biopsy ; Child ; Cyclophosphamide ; Diagnosis ; Dyspnea ; Emergency Service, Hospital ; Female ; Glomerulonephritis ; Hematuria ; Hemoptysis ; Hemorrhage ; Hepatolenticular Degeneration ; Humans ; Penicillamine ; Peroxidase ; Plasmapheresis ; Proteinuria ; Trientine ; Vasculitis

Nephrotic syndrome in the first year of life, characterized by renal dysfunction and proteinuria, is associated with a heterogeneous group of disorders. These disorders are often related to genetic mutations, but the syndrome can also be caused by a variety of other diseases. We report an infant with nephrotic syndrome associated with a neuroblastoma. A 6-month-old girl was admitted with a 10% weight loss over 10 days and nephrotic-range proteinuria. She was ill-looking, and her blood pressure was higher than normal for her age. Her cystatin-C glomerular filtration rate was decreased, and levels of plasma renin, aldosterone, and catecholamines were elevated. Renal ultrasonography and abdominal computed tomography showed a retroperitoneal prevertebral mass encasing both renal arteries and the left renal vein. The mass was partially resected laparoscopically, and the pathologic diagnosis was neuroblastoma. Findings on a simultaneous renal biopsy were unremarkable. The patient was treated with chemotherapy and several anti-hypertensive drugs, including an alpha blocker. Two months later, the mass had decreased in size and the proteinuria and hypertension were gradually improving. In an infant with abnormal renin-angiotensin system activation, severe hypertension, and nephrotic-range proteinuria, neuroblastoma can be considered in the differential diagnosis.
Aldosterone ; Antihypertensive Agents ; Biopsy ; Blood Pressure ; Catecholamines ; Diagnosis ; Diagnosis, Differential ; Drug Therapy ; Female ; Glomerular Filtration Rate ; Humans ; Hypertension ; Infant ; Nephrotic Syndrome ; Neuroblastoma ; Plasma ; Proteinuria ; Renal Artery ; Renal Veins ; Renin ; Renin-Angiotensin System ; Ultrasonography ; Weight Loss

C4 glomerulopathy is a recently introduced entity that presents with bright C4d staining and minimal or absent immunoglobulin and C3 staining. We report a case of a 62-year-old man with C4 glomerulonephritis (GN) and uveitis. He presented to the nephrology department with proteinuria and hematuria. The patient also had intermediate uveitis along with proteinuria and hematuria. A kidney biopsy that was performed in light of continuing proteinuria and hematuria showed a focal proliferative, focal sclerotic glomerulopathy pattern on light microscopy, absent staining for immunoglobulin or C3 by immunofluorescence microscopy, with bright staining for C4d on immunohistochemistry, and electron-dense deposits on electron microscopy. Consequently, C4 GN was suggested as the pathologic diagnosis. Although laser microdissection and mass spectrometry for glomerular deposit and pathologic evaluation of the retinal tissue were not performed, this is the first report of C4 GN in Korea and the first case of coexisting C4 GN and uveitis in the English literature.
Biopsy ; Diagnosis ; Glomerulonephritis* ; Hematuria ; Humans ; Immunoglobulins ; Immunohistochemistry ; Kidney ; Korea ; Mass Spectrometry ; Microdissection ; Microscopy ; Microscopy, Electron ; Microscopy, Fluorescence ; Middle Aged ; Nephrology ; Proteinuria ; Retinaldehyde ; Uveitis ; Uveitis, Intermediate*

BACKGROUND: 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. METHODS: 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. RESULTS: 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, P = 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 (P = 0.004). The probabilities of spontaneous remission were higher in anti-PLA2R-negative patients compared with anti-PLA2R-positive patients (P < 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. CONCLUSION: Detection of anti-PLA2R antibodies at diagnosis in patients with primary MN can predict prognosis and guide treatment decisions.
Antibodies ; Diagnosis ; Enzyme-Linked Immunosorbent Assay ; Follow-Up Studies ; Glomerulonephritis, Membranous* ; Humans ; Incidence ; Multivariate Analysis ; Prognosis ; Proteinuria ; Receptors, Phospholipase A2 ; Remission, Spontaneous ; Renal Insufficiency, Chronic ; Risk Factors

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.
Acute Kidney Injury* ; Blood Pressure ; Child* ; Creatinine ; Critical Illness ; Diagnosis ; Follow-Up Studies ; Humans ; Mortality ; Nutritional Support ; Perfusion ; Proteinuria ; Renal Insufficiency, Chronic ; Renal Replacement Therapy* ; Risk Factors

Heavy proteinuria in the nephrotic range is an uncommon, often unrecognized manifestation of graft-versus-host disease (GVHD) following hematopoietic stem cell transplantation. A few isolated case reports have been published in the Korean literature involving a small number of patients who developed membranous nephropathy as GVHD after peripheral blood stem cell transplantation (PBSCT). A 17-year-old female was diagnosed with non-Hodgkin's lymphoma. Following remission, she underwent allogeneic PBSCT. Shortly thereafter, she developed acute GVHD, which was managed by medical therapy with prednisolone and cyclosporine. Approximately 13 months following PBSCT, the patient developed proteinuria without peripheral edema. Pulsed steroid therapy was initiated three times, but her condition did not improve. Twenty months after PBSCT, she developed nephrotic range proteinuria. A renal biopsy was performed, and the diagnosis was histologically consistent with membranous nephropathy. Because the response to steroids was not satisfactory, the dose of cyclosporine was increased. Approximately 3 months after renal biopsy, the proteinuria disappeared. Given the recent increase in the incidence of GVHD-mediated renal disease, in particular, renal biopsy is indispensable to the diagnosis of nephropathy and to the prevention of disease progression.
Adolescent ; Biopsy ; Cyclosporine ; Diagnosis ; Disease Progression ; Edema ; Female ; Glomerulonephritis, Membranous* ; Graft vs Host Disease* ; Hematopoietic Stem Cell Transplantation ; Humans ; Incidence ; Lymphoma, Non-Hodgkin ; Peripheral Blood Stem Cell Transplantation ; Prednisolone ; Proteinuria ; Stem Cells* ; Steroids

Glomerulonephritis (GN) is sometimes associated with infective endocarditis (IE). Bartonella endocarditis is difficult to diagnose because it is rare and cannot be detected by blood culture. This is the first report of cytoplasmic anti-neutrophil cytoplasmic antibody-positive subacute endocarditis-associated GN caused by Bartonella infection in South Korea. A 67-year-old man was hospitalized due to azotemia. He complained of weight loss and anorexia for 6 months. A diagnosis of IE was made based upon echocardiographic detection of vegetations on the mitral and aortic valves and a Bartonella antibody titer of 1:2,048. Renal histology identified focal crescentic GN. Azotemia and proteinuria improved after doxycycline and rifampin treatment combining with steroid therapy.
Aged ; Anorexia ; Aortic Valve ; Azotemia ; Bartonella Infections* ; Bartonella* ; Cytoplasm ; Diagnosis ; Doxycycline ; Echocardiography ; Endocarditis* ; Glomerulonephritis* ; Humans ; Korea ; Proteinuria ; Rifampin ; Weight Loss

Gitelman syndrome is characterized by hypokalemia, metabolic alkalosis, hypocalciuria, and hypomagnesemia. The clinical course of Gitelman syndrome in pregnant women remains unclear, but it is thought to be benign. We report here the first Korean case of atypical eclampsia in a 31-year-old who was diagnosed with Gitelman syndrome incidentally during an antenatal screening test. The patient did well during pregnancy despite significant hypokalemia. At 33 weeks’ gestation, the patient exhibited eclampsia, hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome, and renal insufficiency without significant hypertension or proteinuria. We explain this unusual clinical course through a review of the relevant literature.
Adult ; Alkalosis ; Eclampsia ; Female ; Gitelman Syndrome* ; HELLP Syndrome* ; Hemolysis ; Humans ; Hypertension ; Hypokalemia ; Liver ; Pregnancy ; Pregnant Women ; Prenatal Diagnosis ; Proteinuria ; Renal Insufficiency

Focal segmental glomerulosclerosis (FSGS) in children, which is a kind of nephrotic syndrome showing steroid resistance, usually progresses to a substantial number of end stage renal disease (ESRD). Although the pathogenesis of primary FSGS is unclear, several recent studies have reported that FSGS is associated with circulating immune factors such as soluble urokinase-type plasminogen activator receptor (suPAR) or anti-CD40 autoantibody. We report a successfully treated case of a 19-year-old female patient who experienced a recurrence of primary FSGS. After the diagnosis of FSGS, the patient progressed to ESRD and received a kidney transplantation (KT). Three days later, recurrence was suspected through proteinuria and hypoalbuminemia. She has been performed plasmapheresis and high dose methylprednisolone pulse therapy and shown remission status without increasing proteinuria for four years after KT. In conclusion, strong immunosuppressive therapy may be helpful for a good prognosis of recurrent FSGS, suppressing several immunologic circulating factors related disease pathogenesis.
Child ; Diagnosis ; Female ; Glomerulosclerosis, Focal Segmental* ; Humans ; Hypoalbuminemia ; Immunologic Factors ; Kidney Failure, Chronic ; Kidney Transplantation ; Methylprednisolone* ; Nephrotic Syndrome ; Plasmapheresis* ; Prognosis ; Proteinuria ; Recurrence ; Urokinase-Type Plasminogen Activator ; Young Adult