Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0033687 (proteinuria)
 24,015 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Idiopathic nephrotic syndrome (INS) in childhood is characterized by massive proteinuria and minimal glomerular changes. Most patients with INS respond to steroid therapy. INS is generally regarded as a sporadic disease with favorable outcome. We investigated a distinct subgroup of nephrosis--the familial form of steroid resistant INS (SRN). These patients always progress to end-stage renal failure within a few years and show absence of recurrence of the disease after renal transplantation. The occurrence of the disorder in siblings and the high incidence of inbreeding in these families made an autosomal recessive mode of inheritance very likely. We performed whole genome linkage analysis in nine multiplex families of European or Northern African origin. Our results allowed us to assign a disease locus (SRN1) to a defined chromosomal region on 1q25-1q31, thus confirming the existence of a distinct entity of autosomal recessive nephrosis. Exclusion of linkage to the entire region in one family proves genetic heterogeneity.
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PMID:Mapping a gene (SRN1) to chromosome 1q25-q31 in idiopathic nephrotic syndrome confirms a distinct entity of autosomal recessive nephrosis. 858 95

Idiopathic nephrotic syndrome of childhood is thought to be associated with T lymphocyte dysfunction often triggered by viral infections, with the production of circulating factor(s) resulting in proteinuria. In view of the conflicting evidence of T cell activation and Th1 or Th2 pattern of cytokine synthesis in this disease, this study examined the mRNA expression of interleukin-2 (IL-2), interferon-gamma, IL-4, and IL-13 from CD4+ and CD8+ T cells in steroid-responsive nephrotic patients in relapse and remission. Fifty-five children with steroid-responsive nephrotic syndrome were included in this study, together with 34 normal controls and 24 patient controls with viral infections. RNA was isolated from purified CD4+ or CD8+ cells from peripheral blood and subjected to reverse transcription-PCR. Cytokine mRNA expression was measured semiquantitatively, and a cytokine index was derived from densitometric readings, with cyclophilin as the housekeeping gene. Both cross-sectional and paired data showed an increased CD4+ and CD8+ IL-13 mRNA expression in patients with nephrotic relapse as compared to remission, normal, and patient controls (P < 0.008). This was also associated with increased cytoplasmic IL-13 expression in phorbol myristate acetate/ionomycin-activated CD3+ cells (6.66+/-3.39%) from patients with nephrotic relapse compared to remission (2.59+/-1.35%) (P < 0.0001). However, there was no significant difference in CD4+ or CD8+ IL-2, interferon-gamma and IL-4 mRNA expression. IL-13 is an important T cell cytokine with anti-inflammatory and immunomodulatory functions on B cells and monocytes. It is conceivable that IL-13 may act on monocytes to produce vascular permeability factor(s) involved in the pathogenesis of proteinuria in patients with relapse nephrotic syndrome.
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PMID:Th1 and Th2 cytokine mRNA profiles in childhood nephrotic syndrome: evidence for increased IL-13 mRNA expression in relapse. 1007 3

We report the clinical and pathologic findings in 7 patients with systemic lupus erythematosus and minimal change disease. All 7 patients presented with full nephrotic syndrome including peripheral edema, nephrotic range proteinuria (mean 9.6 g/day), and hypoalbuminemia (mean 1.8 g/dl). In all cases, renal biopsy revealed diffuse foot process effacement in the absence of significant peripheral capillary wall immune deposits, findings consistent with minimal-change disease. In addition, 5 cases displayed mesangial electron-dense deposits, with or without associated mesangial proliferation, consistent with underlying lupus nephritis class II. In all cases, steroid therapy induced a rapid remission of nephrotic syndrome. Minimal change disease is an underrecognized and readily reversible form of nephrotic syndrome in systemic lupus erythematosus. Because it may occur superimposed on mild mesangial proliferative lupus nephritis, this entity may be misinterpreted as an atypical presentation of lupus nephritis class II. Proper recognition of this entity requires careful integration of the renal biopsy immunofluorescence and electron microscopic findings.
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PMID:Minimal change disease in systemic lupus erythematosus. 1186 21

There are few studies that examine, prospectively, the epidemiological profile of glomerulopathy (GP) and its clinicopathological correlation. All patients referred to Al-Amiri renal center in Kuwait from January 1st, 1995 to December 31st, 2001 were screened for GP. Detailed clinical data were collected and serological markers were done. Renal biopsy was performed whenever indicated. During those 7 years, a total of 584 patients were diagnosed, on histological basis, to have GP, 315 of whom were Kuwaiti nationals. During the same period of the study, 26 patients presented with bilateral small kidneys, history of proteinuria > 2 g/day and lacked systemic manifestations of autoimmune disease. Furthermore, 164 patients with clinical manifestations of diabetic glomerulosclerosis were not subjected to kidney biopsy. Hence, the calculated annual incidence rate of GP in Kuwaiti nationals was 34.5 per 100,000 population (PTP). The calculated rate of diabetic glomerulosclerosis was 13.4 PTP and that of nondiabetic 21.1 PTP. The calculated incidence rates of GP increased with age and were twice as high in males compared to females. Vasculitis was more common in elderly males while SLE nephritis was a disease of adults, 88.7% of whom were females. In the subgroup of primary GP, focal segmental glomerulosclerosis was the most common histological lesion accounting for 18.0% of the total biopsies in Kuwaiti patients, yet only 36.8% of those who fulfilled the criteria of primary type. Minimal change disease was the second primary GP (13.0%), followed by immunoglobulin A deposition disease (7.9%) and membranous glomerulonephritis (5%). Autoimmune diseases such as systemic lupus erythematosus (SLE) and vasculitis were common. Interestingly, only 44 of 72 (61.1%) of patients with SLE and 11 of the 62 (17.7%) of patients with vasculitis presented with rapidly progressive glomerulonephritis. On the other hand, 10 of 58 (17.2%) patients with nephroangiosclerosis presented with renal failure and protein excretion > 2 g/day simulating primary GP. Furthermore, only 21 of 40 (52.5%) patients with IgA nephropathy presented with "benign disease". Prospective studies are essential to ascertain the actual incidence and etiology of GP. The loose clinicopathological correlation in GP dictates an aggressive diagnostic approach in its study and management.
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PMID:Glomerulopathy in Kuwait: the spectrum over the past 7 years. 1291 Nov 67

Idiopathic nephrotic syndrome (NS) associated with focal segmental glomerulosclerosis (FSGS) and severe renal function impairment is usually refractory to the conventional treatment and progresses to end-stage renal disease. Herein, we reported 10 patients with NS-FSGS who had initially had CCr 34 +/- 12 mL/min/1.73 m2 (normal 120 mL/min/1.73 m2), FE Mg 7.8 +/- 2.6% (normal 2.2%), 24-h urinary protein 3.1 g (normal <200 mg) and been followed up for over 10 years. The initial intrarenal hemodynamic study revealed a marked elevation of efferent arteriolar resistance (RE 17289 +/- 8636 dyne x s x cm(-5); normal 3000 dyne x s x cm(-5)), intraglomerular hypertension (PG 57 +/- 1 mm Hg; normal 52 mm Hg), hyperfiltration (FF 0.24; normal 0.2), marked reductions in GFR 35 +/- 17 mL/min/1.73 m2, renal plasma flow (RPF 159 +/- 61 mL/min/1.73 m2; normal 600 mL/min/1.73 m2) and peritubular capillary flow (PTCF 123 +/- 57 mL/min/1.73 m2; normal 480 mL/min/1.73 m2). Such a hemodynamic alteration indicated a hemodynamic maladjustment with a preferential constriction at RE. Treatment consists of multidrugs, namely angiotensin converting enzyme inhibitor, calcium channel blocker, antiplatelet and anticoagulant, with or without angiotensin II receptor antagonist. Following the treatment, correction of hemodynamic maladjustment has been achieved which is characterized by reductions in RE 6046 +/- 2191 dyne x s x cm(-5), PG 52 +/- mm Hg, FF 0.19 +/- 0.1 and increments in RPF 341 +/- 118 mL/min/1.73 m2, PTCF 280 +/- 106 mL/min/1.73 m2 and GFR 64 +/- 17 mL/min/1.73 m2. Coinciding with hemodynamic improvement, there has been a steadily increased creatinine clearance and improvement in FE Mg 4.3 +/- 2.6% and suppression of proteinuria 0.29 +/- 0.4 g/24 h after the period of follow-up of greater than 10 years.
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PMID:Hemodynamic maladjustment and disease progression in nephrosis with FSGS. 1535 70

A patient with advanced rectal cancer was complicated by progressing proteinuria and hypoproteinemia. Low anterior resection was a procedure of choice. A surgical specimen obtained by intraoperative renal biopsy showed the findings of minimal change nephrotic syndrome. After surgery, nephropathy remitted promptly and completely. Her pre/postoperative serum level of vascular endothelial growth factor was 1,880/52.3 pg/ml, suggesting its elevation was associated with the nephropathy. Immunohistochemistry revealed strongly expressed tumor vascular endothelial cell growth factor. Minimal change nephrotic syndrome is a rare type of paraneoplastic nephropathy, and successful remission may require therapeutic resection of the underlying tumor, or administration of a vascular endothelial growth factor antagonist if the tumor is unresectable.
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PMID:Rectal cancer with paraneoplastic nephropathy: association of vascular endothelial growth factor. 1566 42

Idiopathic nephrotic syndrome (iNS) with resistance or dependence to steroids is a common disease in children but in spite of an increasing clinical impact its pathogenesis is unknown. We screened for the presence of circulating antibodies against glomerular (podocytes, mesangium) and tubular cells (tubular epithelia) a cohort of 60 children with iNS including 8 patients with a familial trait of iNS or with proven mutation of NPHS1-NPHS2 and 12 with good sensitivity to steroids. Positive sera were found in 8 cases, all belonging to the category without familial trait/molecular defects. The targets of antibodies were characterized with Western blot and MALDI-Mass utilizing beta-hexyl cell extracts separated with two-dimensional electrophoresis. In all cases antibodies of the IgM class were directed against ATP synthase beta chain alone (4 cases) or in combination with actin (3 cases); one child presented IgG against aldose reductase. The clinical picture was nephrotic syndrome with steroid resistance or dependence and variable cyclosporin sensitivity; 3 patients developed end stage renal failure. The basic pathology picture was focal segmental glomerulosclerosis (FSGS) in 4 cases and mesangial proliferative glomerulonephrites with deposition of IgM in 2. Overall, patients with circulating auto-antibodies could not be readely differentiated on clinical grounds with the exception of 3 children who developed positivity for antinuclear antibodies during the follow-up. Affinity-purified IgM from one patient who underwent plasmapheresis for therapeutical pourposes (but not from a normal pool) induced proteinuria in Sprague-Dawley rats and concomitant human IgM deposition within glomeruli. This is the first report of circulating anti-actin/ATP synthase beta chain antibodies in a subset of patients with iNS. Both pathological significance and clinical impact given by the presence of these antibodies and the relationship with other conditions such as lupus-erythematosus, characterized by their presence, must be defined.
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PMID:Circulating anti-actin and anti-ATP synthase antibodies identify a sub-set of patients with idiopathic nephrotic syndrome. 1604 39

Idiopathic nephrotic syndrome in children may be complicated by resistance to steroids with constant proteinuria in diffuse mesangial proliferation (DMP) and focal segmental glomerulosclerosis (FSGS). In our observation, sometimes in children with steroid-resistant nephrotic syndrome, the presence of immature renal glomeruli can be detected (hypercellularity and presence of a constant layer of cubical epithelial cells on the surface of glomerular tufts, without sclerosis, resembling M-stage of glomerulo-genesis). The aim of this study was immunohistochemical analysis of the podo-cyte-associated proteins, particularly ezrin, podocalyxin, synaptopodin and nephrin in glomeruli with and without signs of immaturity in children. In DMP with signs of immaturity podo-cytes situated in the central region of the glomerulus were immunohistochemically negative. The positive reaction was observed exclusively in the most superficial continuous 'layer' of podo-cytes. The unfavourable clinical course of nephrotic syndrome with signs of glomerular immaturity may be a consequence of decreased immunohistochemical expression of cytoskeleton-specific proteins.
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PMID:[Immunohistochemical analysis of podocytopathy with immature glomeruli and glomerulosclerosis in children with nephrotic syndrome]. 1689 1

Minimal change disease (MCD) is a histopathological lesion in the kidney that is most commonly associated with nephrotic syndrome. The majority of the cases are idiopathic. Pathogenesis is not well understood, although T-cell-related mechanisms are implicated. Massive proteinuria leads to hypoalbuminemia, salt retention, disorder of hemostasis, hyperlipidemia and increased susceptibility to infections. Renal biopsy remains the gold standard for diagnosis. MCD is highly responsive to corticosteroids. Other immunosuppressive agents such as cyclophosphamide, cyclosporin, azathioprine and mycophenolate mofetil have been used to treat cases which are resistant to steroids.
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PMID:Minimal change disease: a review. 1719 22

Idiopathic nephrotic syndrome is characterized by glomerular proteinuria in the absence of infiltrating cells or immunoglobulin deposits. Although it is suspected that T cells secrete a circulating factor that leads to proteinuria by altering the permeability of the glomerular filtration barrier, the precise etiology of this syndrome is unknown. Because an animal model that mimics human idiopathic nephrotic syndrome does not exist, we developed a humanized mouse model of the disease by injecting CD34(+) stem cells or CD34(-) peripheral blood mononuclear cells from afflicted patients into immunocompromised mice. Even though both CD34(+) and CD34(-) cells induced the engraftment of human CD45(+) leukocytes in mice, only the injection of CD34(+) stem cells induced albuminuria. Ultrastructural analysis of glomeruli from the resulting proteinuric mice revealed effacement of podocyte foot processes, similar to the pathology observed in the human disease. Therefore, our data suggest that the cells responsible for the pathogenesis of idiopathic nephrotic syndrome are more likely to be immature differentiating cells rather than mature peripheral T cells.
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PMID:A humanized mouse model of idiopathic nephrotic syndrome suggests a pathogenic role for immature cells. 1789 35


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