- The clinical pattern of nephrotic syndrome in children has no effect on the concentration of soluble urokinase receptor (suPAR) in serum and urine. [Journal Article]
- PMPol Merkur Lekarski 2018 Apr 23; 44(262):183-187
- CONCLUSIONS: Serum and urine concentration of suPAR did not different between different clinical patterns of nephrotic syndrome in children, regardless the immunosuppressive treatment used.
- COL4A5 and LAMA5 variants co-inherited in familial hematuria: digenic inheritance or genetic modifier effect? [Journal Article]
- BNBMC Nephrol 2018 May 16; 19(1):114
- CONCLUSIONS: A modifier role of LAMA5 on the background of a hypomorphic Alport syndrome causing mutation is a possible explanation of our findings. Digenic inheritance is another scenario, following the concept that mutations at both loci more accurately explain the spectrum of symptoms, but further investigation is needed under this concept. This is the third report linking a LAMA5 variant with human renal disease and expanding the spectrum of genes involved in glomerular pathologies accompanied by familial hematurias. The cystic phenotype overlaps with that of a mouse model, which carried a Lama5 hypomorphic mutation that caused severely reduced Lama5 protein levels and produced kidney cysts.
- Glucocorticoids in the treatment of patients with primary focal segmental glomerulosclerosis and moderate proteinuria. [Journal Article]
- CEClin Exp Nephrol 2018 May 14
- CONCLUSIONS: Additional glucocorticoids therapy is more efficacious compared to ACEI/ARB alone in the treatment of patients with pFSGS and moderate proteinuria.
- Cryo-EM structure of the cytoplasmic domain of murine transient receptor potential cation channel subfamily C member 6 (TRPC6). [Journal Article]
- JBJ Biol Chem 2018 May 11
- The kidney maintains the internal milieu by regulating the retention and excretion of proteins, ions, and small molecules. The glomerular podocyte forms the slit diaphragm of the ultrafiltration filt...
The kidney maintains the internal milieu by regulating the retention and excretion of proteins, ions, and small molecules. The glomerular podocyte forms the slit diaphragm of the ultrafiltration filter, whose damage leads to progressive kidney failure and focal segmental glomerulosclerosis (FSGS). The canonical transient receptor potential 6 (TRPC6) ion channel is expressed in the podocyte and mutations in its cytoplasmic domain cause FSGS in humans. In vitro evaluation of disease-causing mutations in TRPC6 has revealed that these genetic alterations result in abnormal ion channel gating. However, the mechanism whereby the cytoplasmic domain modulates TRPC6 function is largely unknown. Here we report a cryoEM structure of the cytoplasmic domain of murine TRPC6 at 3.8Å resolution. The cytoplasmic fold of TRPC6 is characterized by an inverted dome-like chamber pierced by four radial horizontal helices that converge into a vertical coiled-coil at the central axis. Unlike in other TRP channels, TRPC6 displays a unique domain swap that occurs at the junction of the horizontal helices and coiled-coil. Multiple FSGS mutations converge at the buried interface between the vertical coiled-coil and the ankyrin repeats, which form the dome, suggesting these regions are critical for allosteric gating modulation. This functionally critical interface is a potential target for drug design. Importantly, dysfunction in other family members leads to learning deficits (TRPC1/4/5) and ataxia (TRPC3). Our data provide a structural framework for the mechanistic investigation of the TRPC family.
- Plasma microRNA panel is a novel biomarker for focal segmental glomerulosclerosis and associated with podocyte apoptosis. [Journal Article]
- CDCell Death Dis 2018 May 10; 9(5):533
- Focal segmental glomerulosclerosis (FSGS) is a frequent glomerular disease, and is the common cause of nephrotic syndrome. However, there is no validated diagnostic blood biomarker for FSGS. Here, we...
Focal segmental glomerulosclerosis (FSGS) is a frequent glomerular disease, and is the common cause of nephrotic syndrome. However, there is no validated diagnostic blood biomarker for FSGS. Here, we performed a real-time PCR-based high-throughput miRNA profiling to identify the plasma signature for FSGS. We found four miRNAs (miR-17, miR-451, miR-106a, and miR-19b) were significantly downregulated in the plasma of FSGS patients (n = 97) compared with healthy controls (n = 124) in the training, validation, and blinded-test phases. The miRNA panel produced an AUC value of 0.82, and was associated with FSGS severity and histologic classification. A three-miRNA panel, including miR-17, miR-451, and miR-106a was related to FSGS remission. Furthermore, the downregulation of plasma-miRNA signature was not detected in disease controls (n = 119) such as IgA nephropathy (IgAN), mesangial proliferative glomerulonephritis (MSPGN), and membranous nephropathy (MN), and the miRNA panel discriminated between FSGS and disease controls. Pathway analysis showed that the four-miRNA panel may cooperatively regulate the pathways involved in the development of FSGS, such as apoptosis. We identified that phosphatase and tensin homolog (PTEN), Bcl-2-like protein 11 (BCL2L11), and chemokine (C-X-C motif) ligand 14 (CXCL14) were targets of miR-106a in human podocyte. Additionally, miR-106a overexpression suppressed podocyte apoptosis in vitro and the downregulation of four-miRNA panel probably resulted in the enhanced apoptosis in podocyte during FSGS development. Taken together, our data show that the plasma-miRNA panel is a potential independent diagnostic and prognostic factor for FSGS. Above miRNAs are involved in FSGS pathogenesis through regulating podocyte apoptosis.
- The renal manifestations of type 4 familial partial lipodystrophy: a case report and review of literature. [Journal Article]
- BNBMC Nephrol 2018 May 10; 19(1):111
- CONCLUSIONS: We report the first case of proteinuria and renal biopsy in a patient with FPLD4. Gene analysis demonstrated a novel heterozygous frameshift mutation in PLIN1 in this patient and her mother. Treatment with ACEI proved to be beneficial.
- Focal segmental glomerulosclerosis with heterozygous apolipoprotein E5 (Glu3Lys). [Journal Article]
- CCCEN Case Rep 2018 May 08
- Apolipoprotein (apo) E5 is a rare apoE isoform. The apoE5 (Glu3Lys) variant, which is caused by the substitution of lysine with glutamic acid at codon 3, has a relative frequency of 0.1% in Japan. Pr...
Apolipoprotein (apo) E5 is a rare apoE isoform. The apoE5 (Glu3Lys) variant, which is caused by the substitution of lysine with glutamic acid at codon 3, has a relative frequency of 0.1% in Japan. Previous studies have reported that apoE5 (Glu3Lys) is associated with hyperlipidemia and cardiovascular diseases, but this isoform has higher LDL receptor-binding activity than that of normal apoE3. Nephropathy associated with apoE5 (Glu3Lys) alone has not yet been reported. We present a case of a 51-year-old man with nephrotic syndrome. On renal biopsy, three glomeruli showed segmental sclerosis with hypertrophy of podocytes and intracapillary marked infiltration of intraglomerular foam cells. These findings were compatible with focal segmental glomerulosclerosis (FSGS). The patient had mild diabetes mellitus and monoclonal gammopathy of undetermined significance, but there were no specific findings of nephrolopathy related to these diseases. Various factors are involved in the pathogenesis of FSGS, including dyslipidemia and apoE activity. Our findings suggest that abnormal lipid metabolism by ApoE5 (Glu3Lys) is involved in the onset of FSGS.
- Clinical Outcomes of Kidney Transplantation in Patients With Biopsy-Proven Glomerulonephritis. [Journal Article]
- TPTransplant Proc 2018; 50(4):1009-1012
- CONCLUSIONS: Recurrent GN remains a significant cause of graft loss in KT recipients. Surveillance of GN recurrence in the KT recipients with biopsy-proven GN can reduce allograft dysfunction.
- Focal segmental glomerulosclerosis in a patient with prefibrotic primary myelofibrosis. [Journal Article]
- BCBMJ Case Rep 2018 May 04; 2018
- We report a case of 56-year-old man presented to us with chief complaints of frothy urine and leg swelling. A urinalysis revealed nephrotic-range proteinuria. Haematological investigations revealed t...
We report a case of 56-year-old man presented to us with chief complaints of frothy urine and leg swelling. A urinalysis revealed nephrotic-range proteinuria. Haematological investigations revealed thrombocytosis, leucocytosis and peripheral blood smear showed a leucoerythroblastic picture. JAK 2 mutation was positive. To confirm the diagnosis of myeloproliferative neoplasm, bone marrow biopsy was done, which was suggestive of primary myelofibrosis. The patient underwent kidney biopsy due to rapidly declining renal function and persistent proteinuria, which was suggestive of focal segmental glomerulosclerosis. Early glomerulopathy is rare in myeloproliferative neoplasm, and aggressive follow-up is required to prevent progression of kidney disease.
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- Spectrum of renal disease in HIV-infected children: report of five cases. [Journal Article]
- PIPaediatr Int Child Health 2018 May 04; :1-6
- There is a paucity of literature on renal diseases associated with HIV infection in Asian countries. Renal disease in HIV-infected children can involve the glomerulus, interstitium, tubules or blood ...
There is a paucity of literature on renal diseases associated with HIV infection in Asian countries. Renal disease in HIV-infected children can involve the glomerulus, interstitium, tubules or blood vessels of the kidney. In this case series, five HIV-infected children with various forms of renal disease are reported. The renal pathology included HIV-associated nephropathy, collapsing focal segmental glomerulosclerosis without tubular changes, tubule-interstitial nephritis and minimal change disease (MCD). Case five fulfilled the classification criteria for childhood polyarteritis nodosa (PAN). It is important to screen all HIV-infected children for renal disease to enable detection at an early stage.