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)

Glomerulonephritis (GN) is a major cause of chronic renal failure (CRF). To evaluate the trends and outcome with modern improved treatment strategies, we retrospectively reviewed the clinical records of 120 patients with biopsy proven primary GN at our center from January 1990 to June 2001. All the biopsy specimens were subjected to light, electron and immunofluorescent microscopy. The recorded clinical parameters included the presenting symptoms, blood pressure readings, complete blood count, urinalysis, 24-hr urinary protein excretion, creatinine clearance besides rendered therapy and the outcome. Focal segmental glomerulosclerosis was the most common GN and accounted for 56 (47.6%) cases. The frequency of other GN cases in our study included IgA GN in 21 (17.5%) patients, membranous GN in 20 (16.7%), minimal change disease (MCD) in 13 (10.8%), membranoproliferative GN in 4 (3.3%), post infection in 4 (3.3%) and rapidly progressive glomerulonephritis (RPGN) in 2 (1.7%). The type of nephropathy had great influence on outcome and response to therapy. The deterioration of patients with FSGS was the fastest of the glomerulopathies, and nine (16.1%) patients developed end-stage renal failure (ESRD). MCD and post infection GN had the best outcome. Corticosteroids alone along with supportive medication conferred good results in MCD, while combined therapies of mycophenolate mofetil (MMF) and/or cyclophosphamide with corticosteroids provided better outcomes in the rest of the GN. RPGN responded well to the cyclophosphamide and the patients did not develop ESRD. Hyperuricemia, high serum creatinine and hypertension predicted worse outcomes. The control of blood pressure and glucose, and treatment of hyperuricemia and hypoalbuminemia had salutary effect on the outcome. We conclude that due to the better delivered care the outcome of primary GN has improved over the years. However, FSGS is still the most frequently encountered primary GN and has the worst outcome. In the present study, combined therapies with corticosteroids and cytotoxic drugs and supportive therapy were associated with better outcome.
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PMID:Spectrum and outcome of primary glomerulonephritis. 1764 79

Identification of the profile of glomerular disease in a particular geographical region is of fundamental academic, clinical and epidemiological importance. It helps in the recognition of specific risk factors and subsequent planning for adequate prevention. In the present study, 1234 consecutive renal biopsies referred to the nephropathology team of Cairo University over two years were retrospectively analyzed. The main indications for biopsy included nephrotic syndrome, persistent sub-nephrotic proteinuria, recurrent hematuria, suspected secondary hypertension, lupus nephritis and acute and chronic renal failure of undetermined etiology. Proliferative forms of glomerulonephritis [GN] (32.1%) and focal and segmental glomerulosclerosis [FSGS] were the most prevalent lesions among patients with the nephrotic syndrome (22.6%). In subjects with sub-nephrotic proteinuria, FSGS was the principal lesion followed by proliferative lesions. Although all forms of GN were encountered in those presenting with recurrent hematuria, mesangioproliferative GN and FSGS were significantly more frequent. IgA glomerular deposits were detected in 9.8% of all GNs and 15% of those presenting with hematuria. One half of the biopsies obtained for the assessment of suspected secondary hypertension showed only changes compatible with the effect of hypertension per se, i.e. nephroangiosclerosis. On the other hand, a parenchymal renal lesion was found in 52.9% of biopsies. The common glomerular pathologies in patients with lupus nephritis were Classes III and IV. Among patients with chronic renal failure, the predominant lesion was chronic interstitial nephritis (32.6%). An acute interstitial inflammatory element was also detected in 8.4% of cases. About one third of the biopsies obtained for acute renal failure showed acute tubular (11%) or cortical (13.2%) necrosis. Another third showed vasculitis (17.6%) or acute interstitial nephritis (14.3%), and the remaining showed chronic lesions in which the rapid deterioration was probably functional.
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PMID:Spectrum of glomerulonephritis in egypt. 1820 34

We analyzed 137 cases of renal biopsies at the Department of Pathology from 2001 to 2007. The average age was 30.6 years (range, 13-72) for males and 32.9 years (range, 11-75) for females. The male to female ratio was 1.6: 1. The most common clinical syndromes for performing renal biopsy were nephrotic syndrome (81.6%) followed by asymptomatic urinary abnormalities (5.8%), nephritic syndrome (3.6%), hypertension (2.9%), chronic kidney disease (2.2%), acute renal failure (2.2%), cirrhosis (0.7%) and transplant rejection (0.7%). The major glomerular diseases in descending order of frequency were membranous glomerulonephritis (MGN; 42.3%), membranoproliferative glomerulonephritis (MPGN; 21.9%), minimal change disease (MCD; 10.2%), focal segmental glomerulosclerosis (FSGS; 8.0%), IgA nephropathy (2.9%), post infectious glomerulonephritis (GN) (2.2%), chronic GN (2.2%), tubulointerstitial nephritis (TIN; 1.5%), lupus nephritis (1.5%), focal proliferative GN (1.5%), Clq nephropathy (1.5%), amyloidosis (1.5%) and other minor form of glomerular diseases (2.8%). The pattern ofglomerulonephritis in our study is different from the reports of other developing countries. It could be due to various races and altered environmental condition. The information obtained from these results can be used as baseline data for making efficient research in Nepalese population in the future. The higher frequency of MGN and MPGN among Nepalese in comparison with other developing countries deserves further evaluation.
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PMID:Hisopathological spectrum of glomerular disease in nepal: a seven-year retrospective study. 1882 37

Corticosteroid immunosuppression has permitted the development of successful allotransplantation; however, corticosteroids are associated significant post-transplant complications. To circumvent these problems, we implemented a protocol of rapid discontinuation of corticosteroids in 19 consecutive pediatric primary kidney transplant recipients. Mean age at time of transplant was 13.4 (+/-4.5) yr, 52.6% were male, 63.2% underwent living donor transplantation. All patients were administered Thymoglobulin [anti-thymocyte globulin (rabbit)] as induction immunosuppression with a rapid tapering dose of corticosteroids (total of five daily doses), and maintained on mycophenolate mofetil and tacrolimus. Two patients had immediate recurrence of primary disease (FSGS), requiring further corticosteroid therapy. Otherwise, remaining 17 patients were maintained off corticosteroids, with excellent graft function; mean baseline eGFR of 112 mL/min/1.73 m(2) (+/-19) at 28 months (+/-14) post-transplantation. There was 100% patient and rejection-free graft survival at 27 months (range 5-58 months) post-transplantation; 47% underwent renal transplant biopsy secondary to acute rise in serum creatinine with or without worsening hypertension. All biopsies had no evidence of acute rejection; 62.5% had findings consistent with tacrolimus toxicity. Renal transplantation utilizing a rapid discontinuation of corticosteroid protocol in pediatric patients appears to be safe and effective, without increasing the risk of acute rejection or graft loss.
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PMID:Rapid discontinuation of corticosteroids in pediatric renal transplantation. 1941 17

Podocin is a critical component of the glomerular slit diaphragm, and genetic mutations lead to both familial and sporadic forms of steroid-resistant nephrotic syndrome. In mice, constitutive absence of podocin leads to rapidly progressive renal disease characterized by mesangiolysis and/or mesangial sclerosis and nephrotic syndrome. Using established Cre-loxP technology, we inactivated podocin in the adult mouse kidney in a podocyte-specific manner. Progressive loss of podocin in the glomerulus recapitulated albuminuria, hypercholesterolemia, hypertension, and renal failure seen in nephrotic syndrome in humans. Lesions of FSGS appeared after 4 wk, with subsequent development of diffuse glomerulosclerosis and tubulointerstitial damage. Interestingly, conditional inactivation of podocin at birth resulted in a gradient of glomerular lesions, including mesangial proliferation, demonstrating a developmental stage dependence of renal histologic patterns of injury. The development of significant albuminuria in this model occurred only after early and focal foot process effacement had progressed to diffuse involvement, with complete absence of podocin immunolabeling at the slit diaphragm. Finally, we identified novel potential mediators and perturbed molecular pathways, including cellular proliferation, in the course of progression of renal disease leading to glomerulosclerosis, using global gene expression profiling.
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PMID:Podocin inactivation in mature kidneys causes focal segmental glomerulosclerosis and nephrotic syndrome. 1976 89

Mapping by admixture linkage disequilibrium (LD) detected strong association between nonmuscle myosin heavy chain 9 gene (MYH9) variants on chromosome 22 and nondiabetic nephropathy in African Americans. MYH9-related variants were posited to be the probable, but not necessarily the definitive, causal variants as a result of impressive statistical evidence of association, renal expression, and a role in autosomal dominant MYH9 disorders characterized by progressive glomerulosclerosis (Epstein and Fechtner syndromes). Dense mapping within MYH9 revealed striking LD patterns and racial variation in risk allele frequencies, suggesting population genetic factors such as selection may be operative in this region. Genovese and colleagues examined large chromosomal regions adjacent to MYH9 using genome-wide association methods and non-HapMap single nucleotide polymorphisms identified in Yoruba from the 1000 Genomes project. Statistically stronger associations were detected between two independent sequence variants in the Apolipoprotein L1 gene (APOL1) and nondiabetic nephropathy in African Americans, with odds ratios of 10.5 in idiopathic FSGS and 7.3 in hypertension-attributed ESRD. These kidney disease risk variants likely rose to high frequency in Africa because they confer resistance to trypanosomal infection and protect from African sleeping sickness. Risk variants in MYH9 and APOL1 are in strong LD, and the genetic risk that was previously attributed to MYH9 may reside, in part or in whole, in APOL1, although more complex models of risk cannot be excluded. This association likely explains racial disparities in nondiabetic nephropathy as a result of the high prevalence of risk alleles in individuals of African ancestry.
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PMID:The apolipoprotein L1 (APOL1) gene and nondiabetic nephropathy in African Americans. 2068 34

Urinary tract infections (UTI) are common in childhood. Presence of pyuria and bacteriuria in an appropriately collected urine sample are diagnostic of UTI. The risk of UTI is increased with an underlying urological abnormality such as vesicoureteral reflux, constipation, and voiding dysfunction. Patients with acute pyelonephritis are at risk of renal scarring and subsequent complications such as hypertension, proteinuria with and without FSGS, pregnancy-related complications and even end-stage renal failure. The relevance and the sequence of the renal imaging following initial UTI, and the role of antimicrobial prophylaxis and surgical intervention are currently undergoing an intense debate. Prompt treatment of UTI and appropriate follow-up of those at increased risk of recurrence and/or renal scarring are important.
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PMID:Managing urinary tract infections. 2140 31

Molecular genetics have revolutionized the understanding of susceptibility to the broad spectrum of kidney diseases with light microscopic appearance of FSGS, particularly in populations with recent African ancestry. These disorders include idiopathic FSGS, HIV-associated nephropathy, severe lupus nephritis, sickle cell nephropathy, and the primary kidney disorder focal global glomerulosclerosis, which had historically been ascribed to systemic hypertension. FSGS was once thought to include a multitude of unrelated disorders with similar histologic appearance. However, variation in the apolipoprotein L1 gene locus is now known to account for the vast majority of such cases in African Americans as well as nearly all the excess risk for FSGS and related forms of progressive nondiabetic nephropathy in populations with recent African ancestry, relative to European ancestry. Inheriting two coding apolipoprotein L1 gene nephropathy risk variants is necessary for susceptibility to CKD; however, these variants alone are insufficient to produce disease. This work reviews the evidence supporting second hits or modifying factors that affect risk for apolipoprotein L1 gene-associated nephropathy and produce the protean manifestations of this common and complex syndrome. Targeting modifiable second factors will lead to preventive therapies for slowing progression of nondiabetic nephropathy in many patients possessing two apolipoprotein L1 gene risk variants. This model of genetic risk coupled with modifiable second hits will serve as a paradigm applicable to patients with CKD of various etiologies as well as a host of other complex disorders.
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PMID:Gene-gene and gene-environment interactions in apolipoprotein L1 gene-associated nephropathy. 2490 90

For a century, nephrosclerosis was ascribed to nonmalignant hypertension and aging. However, it was intuitively perceived that hypertension may follow rather than explain this nephrovasculopathy. Hypertensive nephrosclerosis was long considered a major cause of end-stage renal failure (ESRD). This is especially true in blacks of African descent but not in other ethnic populations. The term 'nephrosclerosis' is still an easy way out to classify a patient with renal insufficiency. This leads to neglect the possibility of an overlooked nephropathy complicated by hypertension and to believe that drastic blood pressure control may retard the progression to ESRD. Several clinical and experimental lines of evidence lead to the understanding that nephrosclerosis, especially in blacks, is a genetic renovasculopathy that precedes the rise in blood pressure. The identification of coding region variants in APOL1 encoding apolipoprotein L-1 in black but also white and Asians opens new lines of research on the genetics of nephroangiosclerosis and of FSGS. Metabolic derangements, such as obesity, oxidative stress, dyslipidemia and atherosclerosis may be considered confounding factors with regard to nephrosclerosis. Histomorphometric studies led to sorting out the lesions due to aging from those stemming from hypertension. They shed new light not only on glomerular lesions that comprise ischemic obsolescence but also on glomerulomegaly and focal-segmental sclerosis, the latter due to a loss of renal autoregulation. It appears that the control of hypertension is not credited with the expected benefit for slowing the decline of renal function. 'Nephrosclerosis' can be considered an umbrella term of poor significance that should be replaced by its pathologic description, that is, arterionephrosclerosis and incite to elucidate the various genetic and metabolic factors that lead to a lesion in quest of a specific disease.
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PMID:Nephrosclerosis: a term in quest of a disease. 2587 43

Two coding sequence variants in the APOL1 gene (G1 and G2) explain much of the increased risk for FSGS, HIV-associated nephropathy, and hypertension-attributed ESRD among people of recent African ancestry. The ApoL1 protein is expressed in a wide variety of cell tissues. It has been assumed that the majority of circulating ApoL1 is produced by the liver, but this has not been shown. Using mass spectrometry, we genotyped and quantified the circulating ApoL1 in two liver transplant recipients whose native APOL1 genotype differed from the genotype of the deceased donors, allowing us to differentiate liver- from nonliver-produced ApoL1. Our findings confirm that the liver is indeed the main source of circulating ApoL1. However, the liver is not the sole source of circulating ApoL1, because we found that residual amounts of native ApoL1 continued to circulate in the blood, even after the liver transplant.
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PMID:Most ApoL1 Is Secreted by the Liver. 2793 78


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