Glomerular changes in microscopic haematuria, studied by quantitative immuno-electron microscopy and in situ zymography

This thesis considers the possible mechanisms of haematuria in cases of thin basement membrane disease and mild forms of IgA nephropathy. The absence of inflammation in both diseases makes it difficult to explain the passage of erythrocytes to the urinary space.;Two main approaches were used. The composition of glomerular basement membrane was evaluated using quantitative immuno-electron microscopy; this was successfully achieved with antibodies against collagen IV, laminin, fibronectin and collagen VI. Possible changes in degradation by proteolytic enzymes were assessed using quantitative in situ zymography, a novel technique where the ability of tissue sections to digest gelatin in a layer of photographic emulsion is measured.;Initial experiments were performed to establish the techniques and to assess sources of variation in the final measurements. Reproducibility studies for immuno-electron microscopy and in situ zymography demonstrated a considerable amount of variation if processing of tissue was performed on separated days.;Study groups included cases of thin basement membrane disease, IgA nephropathy and normal controls. To control for variation in the measurement methods, cases were arranged into triplet groups and handled as a single batch through immuno-electron microscopy and in situ zymography studies.;Thin basement membrane disease cases demonstrated abnormalities in glomerular basement membrane composition, but not in glomerular gelatinolytic activity. Laminin was found to be lower than normal. Fibronectin and type IV collagen showed slight decreases; collagen IV appeared to be more compact in the thinner membranes.;IgA nephropathy cases had higher glomerular gelatinolytic activity than normal cases. The glomerular basement membrane composition was not changed from normal

Childhood primary glomerular diseases in the western region of Saudi Arabia

We report our institute experience on primary glomerular disease in children in the western region of Saudi Arabia over the last 18 years (1988 to 2006). A total of 169 cases were identified as primary glomerular diseases in children and adolescent with age range from first year of life till 18 years. Minimal change disease and focal segmental glomerulosclerosis were the com-monly encountered primary glomerular diseases (20.1%and 19.5% respectively), mesangioprolifera-tive glomerulonephritis IgM nephropathy (14.8%), IgA nephropathy (10.7%), postinfectious glome-rulonephritis (9.5%), membranous glomerulonephritis (7.1%), membranoproliferative glomerulone-phritis (5.9%) and mesangioproliferative glomerulonephritis with negative immunofluorescence (5.9%). The less frequently encountered primary glomerular diseases were congenital nephritic syn-drome Finnish type (2.4%), Alport syndrome (2.4%), dense deposit disease (1.2%), and mesangio-proliferative glomerulonephritis with IgG positive (0.6%). We concluded that minimal change di-sease and focal segmental glomerulosclerosis are the most common primary glomerular disorder en-countered in children in our series and with similar age distribution

Pathological patterns of mesangioproliferative glomerulonephritis seen at a tertiary care center

Background: Mesangioproliferative glomerulonephritis (MesPGN) is a common morphological pattern that encompasses several groups of renal diseases including IgA nephropathy (IgAN), IgM nephropathy (IgMN), lupus nephritis (LN), C1q nephropathy (C1qN) and other entities. Objectives: The aim of this study was to analyze the pathological findings and the clinical features of cases of MesPGN seen at the king Abdulaziz University, in Saudi Arabia. Patients and Methods: A total of 750 percutaneous native renal biopsies were seen at our institution from January 2000 to December 2011. All the cases diagnosed as MesPGN on light microscopy (LM) were retrieved from the archives of pathology. The pathological features and the clinical data of these cases were reviewed. The clinical data was available for 80 cases only. Results: A total of 103 cases (14%) met the inclusion criteria for the diagnosis of MesPGN. The most common diagnostic entity was IgMN (46.6%) followed by IgAN (30%) along with few cases of class II LN, C1qN, minimal change disease (MCD), Alport’s syndrome, focal segmental glomerulosclerosis (FSGS), thin basement membrane disease (TBMD), and fibrillary glomerulonephritis. The most common clinical presentation was nephrotic syndrome seen in 71% of 80 cases, followed by hematuria (14%). Histologically, focal mesangial proliferation was seen in 62% while diffuse proliferation was seen in 38% of the cases. Conclusion: Mesangioproliferative glomerulonephritis is an important cause of nephrotic syndrome in young adults in the western region of Saudi Arabia. Future studies from the region are needed to elucidate the clinical relevance of mesangial cell proliferation to the end stage kidney diseases

Severe acute post-streptococcal glomerulonephritis in an infant

Acute post-streptococcal glomerulonephritis (APSGN) is very rare below the age of two years. We report a 14-month-old girl who presented with frank hematuria and nephrotic syndrome following group A streptococcal pharyngitis (GAS), which was confirmed by laboratory investigations. The patient underwent a renal biopsy to confirm the diagnosis and was treated with prednisolone. The proteinuria and hematuria resolved completely in eight weeks. Our case demonstrates that APSGN should be considered in evaluating hematuria and nephrotic syndrome in infants and children below two years of age

Pattern of steroid resistant nephrotic syndrome in children living in the kingdom of Saudi Arabia: A single center study

Steroid resistant nephrotic syndrome (SRNS) remains a challenge facing pediatric nephrologists. The underlying histopathology usually affects the course of the disease and the response to treatment. We studied the pattern of histopathology in children with SRNS who presented to the King Abdul Aziz University Hospital (KAUH), Jeddah, Saudi Arabia. The records of all children with primary SRNS, who were seen between 2002 and 2007 were reviewed. Only patients who had undergone a renal biopsy were included in the study. The histopathology slides were reviewed by two renal pathologists independently. Patients with congenital nephrotic syndrome, lupus or sickle cell disease, were excluded from the study. Thirty-six children fulfilled the inclusion criteria, and included 25 girls and 11 boys with female to male ratio of 2.3:1. Fifty percent of the children (n=18) were Saudi and the remaining 50&#x0025; were from various other racial backgrounds (9 Asians, 4 Arabs, 2 Africans and 3 from the Far East). Their mean age at presentation was 4.3 &#177; 3.0 years (range 1-12 years). The mean serum albumin at presentation was 15.6 &#177; 7.1 g/L and all of them had 4&#x002B; proteinuria on urinalysis. Five children had elevated serum creatinine at presentation while the mean serum creatinine was 50.4 &#177; 45.6 &#181;mol/L. Three children had low serum complement levels at presentation and none were positive for hepatitis B surface antigen or antinuclear antibody (ANA). The renal histopathology was compatible with focal and segmental glomerulosclerosis (FSGS) in 39&#x0025; (n=14), IgM nephro-pathy in <i>28&#x0025; </i>(n=10), mesengioproliferative glomerulonephritis (MesPGN) in <i>17&#x0025; </i>(n=6), mini-mal change disease (MCD) and C1q nephropathy (C1qNP) in 8&#x0025; each (n=3 &#x002B; 3) and IgA nephro-pathy in <i>3&#x0025; </i>(n=1). Our retrospective review shows that FSGS was the commonest underlying histopathology in children who presented with SRNS followed by IgM nephropathy and other variants of MCD such as MesPGN. C1qNP was the underlying cause in some children

GAPVD1 and ANKFY1 Mutations Implicate RAB5 Regulation iotic Syndrome.n Nephr

BACKGROUND: Steroid-resistant nephrotic syndrome (SRNS) is a frequent cause of CKD. The discovery of monogenic causes of SRNS has revealed specific pathogenetic pathways, but these monogenic causes do not explain all cases of SRNS. METHODS: To identify novel monogenic causes of SRNS, we screened 665 patients by whole-exome sequencing. We then evaluated the RESULTS: We identified conserved, homozygous missense mutations of CONCLUSIONS: Mutations i

Mutations in six nephrosis genes delineate a pathogenic pathway amenable to treatment

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