[Clinical characteristics and prognosis of 12 cases of lupus nephritis complicated with thrombotic microangiopathy]. / 12ä¾‹ç‹¼ç–®æ€§è‚¾ç‚Žåˆå¹¶è¡€æ “æ€§å¾®è¡€ç®¡ç— å˜ä¸´åºŠç‰¹ç‚¹åŠé¢„åŽåˆ†æž.

OBJECTIVES: To investigate the clinical characteristics, pathological features, treatment regimen, and prognosis of children with lupus nephritis (LN) and thrombotic microangiopathy (TMA), as well as the treatment outcome of these children and the clinical and pathological differences between LN children with TMA and those without TMA. METHODS: A retrospective analysis was conducted on 12 children with LN and TMA (TMA group) who were admitted to the Department of Nephrology, Children's Hospital of Nanjing Medical University, from December 2010 to December 2021. Twenty-four LN children without TMA who underwent renal biopsy during the same period were included as the non-TMA group. The two groups were compared in terms of clinical manifestations, laboratory examination results, and pathological results. RESULTS: Among the 12 children with TMA, 8 (67%) had hypertension and 3 (25%) progressed to stage 5 chronic kidney disease. Compared with the non-TMA group, the TMA group had more severe tubulointerstitial damage, a higher Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score at onset, and higher cholesterol levels (P<0.05). There were no significant differences between the two groups in the percentage of crescent bodies and the levels of hemoglobin and platelets (P>0.05). CONCLUSIONS: There is a higher proportion of individuals with hypertension among the children with LN and TMA, as well as more severe tubulointerstitial damage. These children have a higher SLEDAI score and a higher cholesterol level.

Monogenic Causes Identified in 23.68% of Children with Steroid-Resistant Nephrotic Syndrome: A Single-Centre Study.

Introduction: Steroid-resistant nephrotic syndrome (SRNS) is the second most common cause of end-stage kidney disease in children, mostly associated with focal segmental glomerulosclerosis (FSGS). Advances in genomic science have enabled the identification of causative variants in 20-30% of SRNS patients. Methods: We used whole exome sequencing to explore the genetic causes of SRNS in children. Totally, 101 patients with SRNS and 13 patients with nephrotic proteinuria and FSGS were retrospectively enrolled in our hospital between 2018 and 2022. For the known monogenic causes analysis, we generated a known SRNS gene list of 71 genes through reviewing the OMIM database and literature. Results: Causative variants were identified in 23.68% of our cohort, and the most frequently mutated genes in our cohort were WT1 (7/27), NPHS1 (3/27), ADCK4 (3/27), and ANLN (2/27). Five patients carried variants in phenocopy genes, including MYH9, MAFB, TTC21B, AGRN, and FAT4. The variant detection rate was the highest in the two subtype groups with congenital nephrotic syndrome and syndromic SRNS. In total, 68.75% of variants we identified were novel and have not been previously reported in the literature. Conclusion: Comprehensive genetic analysis is key to realizing the clinical benefits of a genetic diagnosis. We suggest that all children with SRNS undergo genetic testing, especially those with early-onset and extrarenal phenotypes.

Diagnosis of cobalamin C deficiency with renal abnormality from onset in a Chinese child by next generation sequencing: A case report.

The aim of the present study was to present the diagnosis and treatment course of a patient with cobalamin C deficiency (cblC) hospitalized with renal function abnormality from the onset. A female, 7-year-old patient who presented with a cough and progressive dyspnea for 1 day was admitted to the Children's Hospital of Nanjing Medical University (Nanjing, China). A routine clinical examination was performed, including physical examination, routine blood and urine tests, blood gas analysis, computed tomography scans of the head, chest and abdomen, electrocardiogram, echocardiography and abdominal ultrasonography. In addition, laboratory tests were performed, including tests for viral infection and markers of autoimmunity, humoral immunity, myocardial enzymes and tumors. Tandem mass analysis and renal biopsy were conducted. Next generation sequencing (NGS) was performed to identify mutated genes, and structural investigation was conducted to identify the key residue mutations in the patient. Routine clinical examination revealed that the patient had multiple organ failure, indicating the presence of metabolic disease. Tandem mass analysis and renal biopsy also indicated that the patient had methylmalonic acidemia (MMA) and thrombotic microangiopathy combined with focal renal cortical necrosis. Furthermore, next-generation sequencing identified the presence of two heterozygous mutations in the MMA cblC type with homocystinuria (MMACHC) gene. Structural analysis demonstrated that the two mutations were in key components of the MMACHC protein. The patient was finally diagnosed with cblC according to the results obtained. In conclusion, NGS may aid in the diagnosis and therapeutic management of cblC with renal abnormality from the onset in children.

Crescentic acute glomerulonephritis with isolated C3 deposition: a case report and review of literature.

An eight-year-old girl, presenting with palpebral edema, gross hematuria, and foam in urine, was admitted to our hospital. Investigations indicated increased serum antistreptolysin O (ASO) and anti-mycoplasma antibody titers. Renal biopsy showed crescentic poststreptococcal acute glomerulonephritis (CPAGN) with isolated C3 deposition in the glomeruli. Electro-microscope examination showed subepithelial deposition of electron dense material. She received the double pulse therapies of methylprednisolone and cyclophosphamide as well as the treatment of oral prednisolone, angiotensin converting enzyme-II (ACE-II) inhibitor, dipyridamole and traditional Chinese medicine. The complete clinical remission was achieved after 9 months. No serious adverse effects were observed during the follow-up. Our findings indicated that CPAGN with isolated C3 deposition might have a favorable prognosis after aggressive immunosuppressive treatment. However, the influence of isolated C3 deposition on CPAGN prognosis remains to be clarified.

Clinico-pathological association of Henoch-Schoenlein purpura nephritis and IgA nephropathy in children.

OBJECTIVE: Henoch-Schonlein purpura nephritis (HSPN) and IgA nephropathy (IgAN) are similar syndromes. We aimed to determine whether the crescent formation/immunocomplex in glomeruli is associated with the differences of the biochemical indexes between HSPN and IgAN. METHODS: We investigated the medical records of 137 HSPN cases and 41 IgAN cases from January 2009 to April 2014 in Nanjing Children's Hospital of Nanjing Medical University. The clinical and pathological data were analyzed and compared between HSPN and IgAN. RESULTS: HSPN patients had markedly higher levels of blood white blood cell (WBC), hemoglobulin (Hb) and platelet (PLT), lower levels of hematuria, blood nitrogen (BUN) and C4 compared with IgAN cases. Crescents formation and C3 deposition in the kidney did not affect these differences. Significantly lower levels of hematuria, blood IgG, IgM and C4 in HSPN compared with IgAN cases were observed among patients with IgG deposition. Markedly higher levels of WBC and Hb, lower levels of hematuria, creatinine (Cr), C4 in HSPN compared with IgAN cases were observed among patients with IgM deposition. No marked differences of the biochemical indexes were noted between HSPN and IgAN cases among patients with C1q deposition. Markedly higher levels of WBC and Hb, lower level of blood C4 in HSPN compared with IgAN cases were observed among patients with fibrogen deposition. CONCLUSIONS: The different levels of biochemical indexes at presentation between HSPN and IgAN may be associated with the deposition of IgG, IgM, C1q and fibrogen in the kidney.