Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Focal and segmental glomerulosclerosis (FSGS) is a common, non-specific renal lesion. Although it is often secondary to other disorders, including HIV infection, obesity, hypertension and diabetes, FSGS also appears as an isolated, idiopathic condition. FSGS is characterized by increased urinary protein excretion and decreasing kidney function. Often, renal insufficiency in affected patients progresses to end-stage renal failure, a highly morbid state requiring either dialysis therapy or kidney transplantation. Here we present evidence implicating mutations in the gene encoding alpha-actinin-4 (ACTN4; ref. 2), an actin-filament crosslinking protein, as the cause of disease in three families with an autosomal dominant form of FSGS. In vitro, mutant alpha-actinin-4 binds filamentous actin (F-actin) more strongly than does wild-type alpha-actinin-4. Regulation of the actin cytoskeleton of glomerular podocytes may be altered in this group of patients. Our results have implications for understanding the role of the cytoskeleton in the pathophysiology of kidney disease and may lead to a better understanding of the genetic basis of susceptibility to kidney damage.
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PMID:Mutations in ACTN4, encoding alpha-actinin-4, cause familial focal segmental glomerulosclerosis. 1070 Jan 77

This study examines the clinical features, pathologic findings, and outcome of 24 patients with biopsy-proven lithium toxicity. The patient population was 50% male, 87.5% Caucasian, and had a mean age of 42.5 yr (range, 26 to 57). Mean duration of lithium therapy for bipolar disorder was 13.6 yr (range, 2 to 25). All patients were biopsied for renal insufficiency (mean serum creatinine 2.8 mg/dl; range, 1.3 to 8.0), with associated proteinuria >1.0 g/d in 41.7%. Nephrotic proteinuria (>3.0 g/d) was present in 25%. Other features included nephrogenic diabetes insipidus in 87% and hypertension in 33.3%. Renal biopsy revealed a chronic tubulointerstitial nephropathy in 100%, with associated cortical and medullary tubular cysts (62.5%) or dilatation (33.3%). All of the renal cysts stained for epithelial membrane antigen, while 51.4% stained with lectin Arachis hypogaea, and only 3.8% stained with Tetragonolobus purpureas, indicating they originated from distal and collecting tubules. The degree of tubular atrophy and interstitial fibrosis was graded as severe in 58.3%, moderate in 37.5%, and mild in 4.2% of cases. There was a surprisingly high prevalence of focal segmental glomerulosclerosis (50%) and global glomerulosclerosis (100%), sometimes of equivalent severity to the chronic tubulointerstitial disease. The significant degree of foot process effacement (mean 34%, five of 14 cases with >50%) suggests a potential direct glomerular toxicity. Focal segmental glomerulosclerosis correlated with proteinuria >1.0 g/d (P = 0.0014, Fisher exact test). Despite discontinuation of lithium, seven of nine patients with initial serum creatinine values >2.5 mg/dl progressed to end-stage renal disease (ESRD). Only three patients, all with initial serum creatinine <2.1 mg/dl, had subsequent improvement in renal function. By Kaplan-Meier survival analysis, the only significant predictor of progression to ESRD was serum creatinine >2.5 mg/dl at biopsy (P = 0. 008). In conclusion, lithium nephrotoxicity primarily targets distal and collecting tubules, with a higher incidence of proteinuria and associated glomerular pathology than recognized previously. Renal dysfunction is often irreversible despite lithium withdrawal, and early detection is essential to prevent progression to ESRD.
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PMID:Lithium nephrotoxicity: a progressive combined glomerular and tubulointerstitial nephropathy. 1090 57

Focal segmental glomerulosclerosis (FSGS) is a glomerular disease of varying severity. Most patients, however, develop end-stage renal failure within 10 years from clinical onset. In this retrospective study, the outcome of immunosuppressive treatment in 22 adult patients with biopsy-proven primary FSGS was evaluated. Eleven patients were treated with prednisone, azathioprine and chlorambucil (group A) and 11 with prednisone and pulse cyclophosphamide (group B). The nephrotic syndrome (NS) was found in 4 patients from the group A and in 3 patients from the group B, arterial hypertension in 8 and 9 patients, respectively. During the follow-up lasting about 50 months as the mean, 70% of the patients did not respond to the treatment and complete remission was obtained only in 3 patients from the group B. On the other hand, 7 patients progressed into CFR. Among them, 5 out of 7 patients with NS (4 from the group A) needed dialysis treatment or doubled their Pcr after a mean of 38 months. This study confirms poor outcome of immunosuppressive treatment in patients with FSGS. However, of the two forms of treatment used in the study, the response appeared to be better and more lasting with cyclophosphamide than with azathioprine and chlorambucil. Corticosteroids associated with pulse cyclophosphamide therapy seems to improve the chances of remission and to protect from renal dysfunction.
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PMID:[Comparative study of two immunosuppressive treatment methods in patients with focal segmental glomerulosclerosis]. 1107 46

There are few data regarding adolescent-onset nephrotic syndrome (NS) and no guidelines for biopsy criteria and treatment protocol. This study was conducted to analyze the clinical spectrum of adolescent-onset NS and evaluate possible biopsy criteria in these children. A prospective analysis was carried out on all patients with idiopathic NS (fulfilling the ISKDC criteria) with onset between 1 and 18 years of age. They were evaluated clinically, followed by biochemical investigations and kidney biopsy. These characteristics of patients with onset between 1 and 12 years (group A) were compared with the same parameters in patients with onset between 12 and 18 years of age (group B) referred to our hospital over the same period. Among all clinical parameters, microhematuria was significantly more prevalent in adolescents (P<0.001). Kidney biopsy was performed in 88% of adolescent patients. Focal segmental glomerulosclerosis (FSGS) was the most-common histopathology in group B (46.3%) compared with minimal change disease (MCD) in group A (42.9%). Group B had a significantly higher frequency of membranoproliferative glomerulonephritis (MPGN) (P<0.005) and a significantly lower frequency of MCD (P<0.001). The biochemical parameters at the onset were similar. On comparing microhematuria, hypertension, and renal insufficiency at presentation, we observed that two or more of these features were present in all patients with MPGN and only in 19.6% of adolescents with MCD, mesangioproliferative glomerulonephritis, and FSGS. The frequency of steroid resistance was significantly higher in group B (P<0.001). In conclusion, adolescent-onset NS differs from the childhood variety in having a significantly higher frequency of hematuria, steroid resistance, and evidence of non-MCD, especially MPGN, on histopathology. Kidney biopsy can be restricted to those adolescents who have at least two abnormal clinical/biochemical features or are steroid non-responders.
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PMID:Spectrum of adolescent-onset nephrotic syndrome in Indian children. 1179 97

Focal segmental glomerulosclerosis (FSGS), the leading glomerular cause of the nephrotic syndrome among African Americans, is typically associated with edema, proteinuria, hypertension, microscopic hematuria, and renal insufficiency. Recent studies suggest that either the incidence of FSGS has increased or an increased number of biopsies of African American patients have made the diagnosis more common. The collapsing variant of FSGS, which occurs more commonly in African Americans than in whites, carries an especially poor prognosis with respect to renal survival. Although the pathogenesis of FSGS is not well understood, the fact that it frequently recurs early after transplantation has led to speculation that patients with FSGS may have a circulating factor that leads to increased glomerular permeability. There are no randomized control trials of treatment regimens for FSGS. Steroids, alkylating agents, and cyclosporin have all been used with variable results to treat FSGS.
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PMID:Focal segmental glomerulosclerosis in African Americans. 1186 85

Nephrotic syndrome in children is a clinical manifestation of different histopathological subtypes. There is a paucity of recent large studies dealing with the histopathological spectrum from developing countries. A prospective study was performed from January 1990 to December 2000 at our center, involving 600 children (with age of onset up to 16 years) with idiopathic nephrotic syndrome (INS). The objectives were: (1) to study the histopathological distribution of different subtypes of INS and (2) to compare the clinical and biochemical parameters at the time of diagnosis of minimal change disease (MCD) with non-MCD subtypes. For the purpose of this study we analyzed only those children with INS who underwent biopsies. The study group included 290 children in which adequate biopsy reports were available. There were 213 males and 77 females. Mean age at onset of INS was 7.9+5.1 years. Facial edema was found in 286 (98.6%), microhematuria in 120 (41.3%), gross hematuria in 7 (2.5%), and hypertension in 77(26.8%) patients. All patients of the study group were seronegative for HBsAg and HIV. Focal and segmental glomerulosclerosis (FSGS) was the most common histopathological subtype, occurring in 110 of 290 children (38%). Other subtypes included MCD in 95 children (32%), membranoproliferative glomerulonephritis (MPGN) in 44 children (15%), mesangioproliferative glomerulonephritis in 33 children (11%), membranous glomerulonephritis in 5 children (2%), and diffuse mesangial sclerosis in 3 children (1%). In children under 8 years of age, MCD was the most common entity, whereas FSGS predominated in children with age at onset greater than 8 years. The age at onset of nephrotic syndrome was significantly higher in the non-MCD group than the MCD group. The incidence of hypertension, microhematuria, and gross hematuria was significantly lower in the MCD group. MCD remains the most common histopathological subtype in Indian children with INS and onset under 8 years of age. The incidence of MPGN continues to be high. MCD can be differentiated from non-MCD subtype by younger age at onset, absence of hypertension, and absence of microscopic hematuria.
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PMID:Histopathological spectrum of childhood nephrotic syndrome in Indian children. 1274 93

We analyzed 19 patients with focal segmental glomerulosclerosis (FSGS): 11 males and 8 females (mean age 38.3 yrs. (SD 16.4), who were under observation for 39.4 months (SD 17.2). At the moment of renal biopsy 73.7% of patients had arterial hypertension, 52.6%--nephrotic proteinuria, 36.9%--chronic renal failure. Global glomerulosclerosis was present in 14 biopsies (73.7%), and intersticial fibrosis--in 13 biopsies (68.4%). The results of analysis showed multiple risk factors for progression of renal failure: initial renal failure (p=0.005), proteinuria (> or =3 g/l) (p=0.005), expressed glomerulosclerosis (p=0.005) and expressed interstitial fibrosis (p=0.034). Focal segmental glomerulosclerosis were found to have a relatively bad long-term prognosis--the renal survival rate in 5 years was 77.8%. Kaplan-Meier survival analysis showed that expressed glomerulosclerosis was risk factor (logrank p=0.016, Breslov p=0.043) associated with end-stage renal disease in 5 years.
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PMID:[Focal segmental glomerulosclerosis: prognosis of chronic renal failure]. 1276 15

Focal segmental glomerulosclerosis represents a finding in several renal disorders, characterized by proteinuria and sometimes by arterial hypertension and progressive decline in renal function. There are primary (idiopathic and familial) and secundary forms. In the last 20 years several familial cases has been reported, with a great genetic heterogeneity (dominant and recessive forms) and with multiple associations with particular MHC class-I and class-II gene loci, being Al, DR3 o DR7 the most frequently reported. We described three members of same family with focal segmental hyalinosis that shared the HLA haplotype A31 B61 DR13. This association has not been described previously. We highlight that genetic and acquired factors (obesity, hypertension...) could have importance in the development of progressive renal failure in these patients.
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PMID:[Familial focal and segmentary hyalinosis]. 1277 84

Adrenal myelolipomas are rare benign tumors, usually discovered by chance in patients with hypertension, obesity or various endocrine disorders. Focal segmental glomerulosclerosis (FSGS) can occur as a primary disease or in a variety of secondary settings. So far, no association between the two conditions has been described. We report a case of a woman admitted for nephrotic syndrome, in which a coexistence of FSGS and bilateral large adrenal myelolipomas was revealed.
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PMID:Focal segmental glomerulosclerosis in a patient with large bilateral asymptomatic adrenal myelolipomas. 1466 65

Focal segmental glomerulosclerosis (FSGS) is a common pattern of renal injury, seen as both a primary disorder and as a consequence of underlying insults such as diabetes, HIV infection, and hypertension. Point mutations in the alpha-actinin-4 gene ACTN4 cause an autosomal dominant form of human FSGS. We characterized the biological effect of these mutations by biochemical assays, cell-based studies, and the development of a new mouse model. We found that a fraction of the mutant protein forms large aggregates with a high sedimentation coefficient. Localization of mutant alpha-actinin-4 in transfected and injected cells, as well as in situ glomeruli, showed aggregates of the mutant protein. Video microscopy showed the mutant alpha-actinin-4 to be markedly less dynamic than the wild-type protein. We developed a "knockin" mouse model by replacing Actn4 with a copy of the gene bearing an FSGS-associated point mutation. We used cells from these mice to show increased degradation of mutant alpha-actinin-4, mediated, at least in part, by the ubiquitin-proteasome pathway. We correlate these findings with studies of alpha-actinin-4 expression in human samples. "Knockin" mice with a disease-associated Actn4 mutation develop a phenotype similar to that observed in humans. Comparison of the phenotype in wild-type, heterozygous, and homozygous Actn4 "knockin" and "knockout" mice, together with our in vitro data, suggests that the phenotypes in mice and humans involve both gain-of-function and loss-of-function mechanisms.
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PMID:Alpha-actinin-4-mediated FSGS: an inherited kidney disease caused by an aggregated and rapidly degraded cytoskeletal protein. 1520 19


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