- IgM Myeloma: case report and literature review. [Journal Article]
- ABAnn Biol Clin (Paris) 2018 Oct 01; 76(5):575-578
- The presence of serum monoclonal IgM is often associated with the diagnosis of Waldenström macroglobulinemia (WM) or other chronic lymphoproliferative disorders. IgM myeloma is a rare entity (0.5%). ...
The presence of serum monoclonal IgM is often associated with the diagnosis of Waldenström macroglobulinemia (WM) or other chronic lymphoproliferative disorders. IgM myeloma is a rare entity (0.5%). We report the case of an IgM myeloma complicated by systemic amyloidosis AL, with an impure nephrotic syndrome and a factor FX deficiency.
- Network analysis of membranous glomerulonephritis based on metabolomics data. [Journal Article]
- MMMol Med Rep 2018 Sep 12
- Membranous glomerulonephritis (MGN) is one of the most frequent causes of nephrotic syndrome in adults. It is characterized by the thickening of the glomerular basement membrane in the renal tissue. ...
Membranous glomerulonephritis (MGN) is one of the most frequent causes of nephrotic syndrome in adults. It is characterized by the thickening of the glomerular basement membrane in the renal tissue. The current diagnosis of MGN is based on renal biopsy and the detection of antibodies to the few podocyte antigens. Due to the limitations of the current diagnostic methods, including invasiveness and the lack of sensitivity of the current biomarkers, there is a requirement to identify more applicable biomarkers. The present study aimed to identify diagnostic metabolites that are involved in the development of the disease using topological features in the component‑reaction‑enzyme‑gene (CREG) network for MGN. Significant differential metabolites in MGN compared with healthy controls were identified using proton nuclear magnetic resonance and gas chromatography‑mass spectrometry techniques, and multivariate analysis. The CREG network for MGN was constructed, and metabolites with a high centrality and a striking fold‑change in patients, compared with healthy controls, were introduced as putative diagnostic biomarkers. In addition, a protein‑protein interaction (PPI) network, which was based on proteins associated with MGN, was built and analyzed using PPI analysis methods, including molecular complex detection and ClueGene Ontology. A total of 26 metabolites were identified as hub nodes in the CREG network, 13 of which had salient centrality and fold‑changes: Dopamine, carnosine, fumarate, nicotinamide D‑ribonucleotide, adenosine monophosphate, pyridoxal, deoxyguanosine triphosphate, L‑citrulline, nicotinamide, phenylalanine, deoxyuridine, tryptamine and succinate. A total of 13 subnetworks were identified using PPI analysis. In total, two of the clusters contained seed proteins (phenylalanine‑4‑hydroxlylase and cystathionine γ‑lyase) that were associated with MGN based on the CREG network. The following biological processes associated with MGN were identified using gene ontology analysis: 'Pyrimidine‑containing compound biosynthetic process', 'purine ribonucleoside metabolic process', 'nucleoside catabolic process', 'ribonucleoside metabolic process' and 'aromatic amino acid family metabolic process'. The results of the present study may be helpful in the diagnostic and therapeutic procedures of MGN. However, validation is required in the future.
- An update on LDL apheresis for nephrotic syndrome. [Review]
- PNPediatr Nephrol 2018 Sep 14
- Low-density lipoprotein (LDL) apheresis has been used increasingly in clinical practice for the treatment of renal diseases with nephrotic syndrome (NS), specifically focal segmental glomeruloscleros...
Low-density lipoprotein (LDL) apheresis has been used increasingly in clinical practice for the treatment of renal diseases with nephrotic syndrome (NS), specifically focal segmental glomerulosclerosis (FSGS). Persistent hyperlipidemia for prolonged periods is nephrotoxic and leads to chronic progressive glomerular and tubulointerstitial injury. Effective management of hyperlipidemia with HMG-CoA reductase inhibitors or LDL apheresis in drug-resistant NS patients may prevent the progression of renal disease and, in some patients, resolution of NS symptoms. Available literature reveals beneficial effects of LDL apheresis for NS refractory to drug therapy. Here we update on the current understanding of lipid nephrotoxicity and application of LDL apheresis to prevent progression of renal diseases.
- Management of children with congenital nephrotic syndrome: challenging treatment paradigms. [Journal Article]
- NDNephrol Dial Transplant 2018 Jun 21
- CONCLUSIONS: An individualized, stepwise approach with prolonged conservative management may be a reasonable alternative to early bilateral nephrectomies and dialysis in children with CNS and NPHS1 mutations. Further prospective studies are needed to define indications for unilateral nephrectomy.
- Characterization of a novel disease-associated mutation within NPHS1 and its effects on nephrin phosphorylation and signaling. [Journal Article]
- PlosPLoS One 2018; 13(9):e0203905
- Mutations in the transmembrane protein nephrin (encoded by NPHS1) underlie nearly half of all cases of congenital nephrotic syndrome (CNS), which is caused by aberrations in the blood filtering funct...
Mutations in the transmembrane protein nephrin (encoded by NPHS1) underlie nearly half of all cases of congenital nephrotic syndrome (CNS), which is caused by aberrations in the blood filtering function of glomerular podocytes. Nephrin directly contributes to the structure of the filtration barrier, and it also serves as a signaling scaffold in podocytes, undergoing tyrosine phosphorylation on its cytoplasmic tail to recruit intracellular effector proteins. Nephrin phosphorylation is lost in several human and experimental models of glomerular disease, and genetic studies have confirmed its importance in maintenance of the filtration barrier. To date, however, the effect of CNS-associated NPHS1 variants on nephrin phosphorylation remains to be determined, which hampers genotype-phenotype correlations. Here, we have characterized a novel nephrin sequence variant, A419T, which is expressed along with C623F in a patient presenting with CNS. Nephrin localization is altered in kidney biopsies, and we further demonstrate reduced surface expression and ER retention of A419T and C623F in cultured cells. Moreover, we show that both mutations impair nephrin tyrosine phosphorylation, and they exert dominant negative effects on wildtype nephrin signaling. Our findings thus reveal that missense mutations in the nephrin extracellular region can impact nephrin signaling, and they uncover a potential pathomechanism to explain the spectrum of clinical severity seen with mild NPHS1 mutations.
- Modified Huangqi Chifeng decoction inhibits excessive autophagy to protect against Doxorubicin-induced nephrotic syndrome in rats via the PI3K/mTOR signaling pathway. [Journal Article]
- ETExp Ther Med 2018; 16(3):2490-2498
- The aim of the present study was to investigate whether modified Huangqi Chifeng decoction (MHCD) could be an effective treatment against Doxorubicin-induced nephrosis in rats and whether it regulate...
The aim of the present study was to investigate whether modified Huangqi Chifeng decoction (MHCD) could be an effective treatment against Doxorubicin-induced nephrosis in rats and whether it regulates autophagy via the phosphoinositide-3 kinase/mammalian target of rapamycin (PI3K/mTOR) signaling pathway. A total of 40 male Sprague-Dawley rats were randomly divided into blank, model, telmisartan and MHCD groups. The rat model of nephrosis was induced by intragastric administration of Doxorubicin for 8 weeks. Rats were housed in metabolic cages and urine was collected once every 2 weeks to measure 24-h protein levels. Blood samples were obtained from the abdominal aorta and levels of albumin (ALB), total cholesterol (TCH), triacylglyceride (TG) and serum creatinine (Scr) were assessed. Renal pathological changes were examined using hematoxylin-eosin, Masson's trichome and periodic acid-Schiff staining. Podocytes and autophagosomes were observed using an electron microscope. The expression and distribution of microtubule-associated proteins 1A/1B light chain 3B (LC3), LC3-I, LC3-II, beclin-1, PI3K and mTOR were determined using immunohistochemistry and western blotting. At weeks 6 and 8, 24-h proteinuria significantly decreased in the MHCD group compared with the model group (P<0.05). Compared with the model group, the MHCD group exhibited significantly reduced levels of TG, TCH and Scr, as well as significantly increased ALB levels (P<0.05). MHCD was demonstrated to prevent glomerular and podocyte injury. The number of autophagosomes was significantly decreased and the expression of beclin-1, LC3, LC3-I and LC3-II was inhibited following MHCD treatment compared with the model group (P<0.05). MHCD treatment significantly increased the expression of PI3K and mTOR in Doxorubicin nephrotic rats compared with the model group (P<0.05). In conclusion, MHCD was demonstrated to ameliorate proteinuria and protect against glomerular and podocyte injury by inhibiting excessive autophagy via the PI3K/mTOR signaling pathway.
- Idiopathic Nephrotic Syndrome: Characteristics and Identification of Prognostic Factors. [Journal Article]
- JCJ Clin Med 2018 Sep 09; 7(9)
- There are various histopathological forms of idiopathic nephrotic syndrome, including minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS). Whereas some relapse predictor factor...
There are various histopathological forms of idiopathic nephrotic syndrome, including minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS). Whereas some relapse predictor factors have been identified in renal transplantation, the clinical future of idiopathic nephrotic syndrome in the native kidney remains uncertain. We designed a multicentric retrospective descriptive cohort study including all patients aged 15 years and over whose renal biopsy confirmed MCD or FSGS between January 2007 and December 2014. We studied 165 patients with idiopathic nephrotic syndrome; 97 with MCD and 68 with FSGS. In the MCD cohort, 91.7% of patients were treated with corticosteroids for a median total duration of 13 months. During 45 months of follow-up, 92.8% of patients achieved remission and 45.5% experienced relapse. In this cohort, 5% of patients experienced terminal kidney disease. With respect to FSGS patients, 51.5% were treated with corticosteroids for a median total duration of 15 months. During 66 months of follow-up, 73.5% of patients achieved remission and 20% experienced relapse. In this cohort, 26.5% of patients experienced terminal kidney disease. No statistical association was observed between clinical and biological initial presentation and relapse occurrence. This study describes the characteristics of a cohort of patients with the nephrotic idiopathic syndromes of MCD and FSGS from the time of renal biopsy and throughout follow-up.
- Study protocol: high-dose mizoribine with prednisolone therapy in short-term relapsing steroid-sensitive nephrotic syndrome to prevent frequent relapse (JSKDC05 trial). [Journal Article]
- BNBMC Nephrol 2018 Sep 10; 19(1):223
- CONCLUSIONS: The results provide important data on use of high-dose mizoribine to prevent SSNS patients from shifting to FRNS. Since blood concentrations of mizoribine have not been investigated in detail until now, there is a possibility that mizoribine is underestimated in favor of other immunosuppressive drugs. In future, high-dose mizoribine therapy may lead to prevention of relapse in children at high risk of FRNS, and to decreased total dose of prednisolone.
- Disseminated Strongyloidiasis in Association with Nephrotic Syndrome. [Journal Article]
- CRCase Rep Nephrol Dial 2018 May-Aug; 8(2):155-160
- Strongyloidiasis is a well-known parasitic infection endemic in tropical and subtropical areas of the world. While most infected individuals are asymptomatic, strongyloidiasis-related glomerulopathy ...
Strongyloidiasis is a well-known parasitic infection endemic in tropical and subtropical areas of the world. While most infected individuals are asymptomatic, strongyloidiasis-related glomerulopathy has not been well documented. We present a case of disseminated strongyloidiasis in a patient with minimal change nephrotic syndrome treated with high-dose corticosteroids. The remission of nephrotic syndrome after treatment of strongyloidiasis suggests a possible causal relationship between Strongyloides and nephrotic syndrome.
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- Risk factors for early B cell recovery following single-dose rituximab therapy in Japanese children with steroid-dependent nephrotic syndrome. [Letter]
- PNPediatr Nephrol 2018 Sep 08