No efficient treatment exists for nephrotic syndrome (NS), a frequent cause of chronic kidney disease. Here we show mutations in six different genes (MAGI2, TNS2, DLC1, CDK20, ITSN1, ITSN2) as causing NS in 17 families with partially treatment-sensitive NS (pTSNS). These proteins interact and we delineate their roles in Rho-like small GTPase (RLSG) activity, and demonstrate deficiency for mutants of pTSNS patients. We find that CDK20 regulates DLC1. Knockdown of MAGI2, DLC1, or CDK20 in cultured podocytes reduces migration rate. Treatment with dexamethasone abolishes RhoA activation by knockdown of DLC1 or CDK20 indicating that steroid treatment in patients with pTSNS and mutations in these genes is mediated by this RLSG module. Furthermore, we discover ITSN1 and ITSN2 as podocytic guanine nucleotide exchange factors for Cdc42. We generate Itsn2-L knockout mice that recapitulate the mild NS phenotype. We, thus, define a functional network of RhoA regulation, thereby revealing potential therapeutic targets.

Although some studies showed a significant increase in lupus nephritis among male systemic lupus erythematosus patients, others showed no difference or contradicting results. Hence, we suggest further studies comparing the disease manifestations between the two genders.

MYH9 (myosin heavy chain 9)-mutation is a frequent genetic disorder among African-Americans and rare in Caucasians that can lead to dramatic deterioration of renal function and as a consequence, end stage renal disease (ESRD). The clinical presentation of MYH9 mutations includes five syndromes: May-Hegglin anomaly, Sebastian, Fechtner, Epstein syndromes and isolated sensorineural deafness. The diagnosis is challenging to establish due to non-specific presentation that requires exclusion of a vast number of other entities. Renal biopsy is not commonly performed but it may reveal non-specific findings such as mesangial expansion with hypercellularity, focal segmental glomerulosclerosis (FSGS) and/or global glomerulosclerosis usually with no immune complex deposition. The immunostaining study for alpha-smooth muscle actin (SMA) can be valuable to perform in patients suspected to have MYH9 mutations in order to detect early FSGS. Additional studies for patients presenting with thrombocytopenia, decreasing glomerular filtration rate, proteinuria and haematuria are suggested. Here, we report a child with classic clinical picture of MYH9 genetic disorder that presented with early focal segmental glomerulosclerosis with possible concurrent C1q nephropathy. This case highlights the importance of kidney biopsy in optimal management of pediatric patients with MYH9 related diseases.

No abstract

Background: Membranous nephropathy (MGN) is one of the most common glomerular disease seen among adults. However, it is a rare histological presentation in pediatric population. In contrast to MGN in adults where primary form is known to be the leading subtype of the disease, secondary cause is more prevailing in children. Case Presentation: We describe a case of an infant presenting with nephrotic syndrome (NS) and negative serology work-up. Kidney biopsy showed the picture of severe diffuse MGN confirmed by light, immunofluorescence and electron microscopy studies. "Full-house" pattern by immunofluorescence, numerous well-demarcated sub-epithelial deposits and tubuloreticular inclusions strongly suggested type V lupus nephritis. Conclusions: NS due to MGN is rarely seen in infancy. Secondary causes such as autoimmune disease or systemic infection need to be considered for appropriate management. ABSTRACT Implication for health policy/practice/research/medical education:Membranous glomerulonephritis is uncommon in children and in contrast to adults, is commonly due to secondary causes. Therefore, extensive investigations in children with membranous nephropathy (MGN) is necessary to rule out the underlying disorders, such as systemic lupus erythematosus or infections. Please cite this paper as: Dokouhaki P, Rakhmetova A, Alabbas A. Infant onset systemic lupus erythematosus presenting as nephrotic syndrome.