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)

Glial cell-derived neurotrophic factor (GDNF) plays an important role in renal development, serving as a trophic factor for outgrowth of the ureteric bud and its continued arborisation. Our previous studies have shown that common variants of the human paired-box 2 (PAX2) gene (a transcriptional activator of GDNF) and rearranged during transfection (RET) gene (encoding the cognate receptor for GDNF) are associated with a subtle reduction in the kidney size of newborns. Since heterozygosity for a mutant GDNF allele causes mild renal hypoplasia and modest hypertension in mice, we considered the possibility that common variants of the GDNF gene might also contribute to renal hypoplasia in humans. We studied the relationship between newborn renal size or umbilical cord cystatin C and 19 common GDNF gene variants [minor allele frequency (MAF) >5%], three single nucleotide polymorphisms (SNPs) related to a putative PAX binding site and one rare SNP (rs36119840 A/G) which changes an amino acid (R93W), based on data from the haplotype map of the human genome (HapMap). However, none of these 23 SNPs was associated with reduced newborn kidney size or function. Among the 163 Caucasians in our cohort, none had the R93W allele.
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PMID:Common variants of the glial cell-derived neurotrophic factor gene do not influence kidney size of the healthy newborn. 1918 20

Serum cystatin C concentration is an alternative measure of kidney function that is less affected by age, sex or muscle mass, and is a more sensitive indicator of early renal dysfunction than creatinine-based estimations of glomerular filtration rate. Cardiovascular sequela increases progressively with the increase in left ventricular mass. Our goal was to evaluate the effect of olmesartan medoxomil on cystatin C levels and left ventricular hypertrophy (LVH) in patients with hypertension. Forty-four newly diagnosed hypertensive patients (27 women and 17 men) were recruited in the study. Olmesartan medoxomil (20mg/day) was started and the patients were followed up for 6 months. Baseline echocardiographic findings (i.e. left ventricular mass index), serum creatinine, urine albumin/creatinine ratio (ACR) and serum cystatin C levels were compared with the levels of these variables measured at the end of 6-month follow-up period. After 6 months of treatment with olmesartan medoxomil, there was a significant reduction in systolic and diastolic blood pressure (p<0.001) and in urine ACR (p=0.04). Mean serum cystatin C levels decreased from 1.61+/-0.24 mg/l to 1.31+/-0.29 mg/l (p<0.001). Olmesartan medoxomil treatment also reduced left ventricular mass index (p<0.001) and LVH (p<0.001). Our findings indicate that olmesartan medoxomil decreases serum cystatin C levels, urine ACR and reduces LVH in patients with hypertension. To our knowledge, this study is the first to show that olmesartan medoxomil decreases serum cystatin C levels, indicating that in patients with essential hypertension it may counteract end organ damage.
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PMID:Effect of olmesartan medoxomil on cystatin C level, left ventricular hypertrophy and diastolic function. 1952 88

The influence of prenatal factors on the development of arterial hypertension has gained considerable interest in recent years. Prenatal dexamethasone exposure was found to induce hypertension and to alter nephron number and size in rodents and sheep. However, it is not clear whether these findings are applicable to nonhuman primates. Thus, we examined the effects of prenatal dexamethasone treatment on blood pressure (BP) and nephron number in marmoset monkeys. Fifty-two marmosets were allotted to 3 groups according to the gestational stage during which their mothers were exposed to oral 5-mg/kg dexamethasone for 7 days (gestation period: 20 weeks): (1) the early dexamethasone group at week 7; (2) the late dexamethasone group at week 13; and (3) the control group. BP was determined by telemetric (n=12) or cuff measurements (n=30), along with cystatin C, proteinuria, and body weight. All of the animals were euthanized at the age of 24 months, and glomerular number and volume were determined. Prenatal exposure to dexamethasone did not lead to a significant difference between the groups with regard to BP, kidney morphology and function, or body weight. BP correlated significantly with body weight, relative kidney weight, and mean glomerular volume and the body weight with the glomerular volume regardless of dexamethasone treatment. In conclusion, prenatal exposure to dexamethasone in marmosets does not, in contrast to other mammals studied, result in hypertension or changes in kidney morphology. Our data support the role of body weight as a predictor of elevated glomerular volume and BP development rather than prenatal dexamethasone exposure.
Hypertension 2009 Nov
PMID:Prenatal dexamethasone exposure does not alter blood pressure and nephron number in the young adult marmoset monkey. 1977 Apr 6

We evaluated renal function at a median follow-up of 18 (range 10.3-22.1) years after total body irradiation in 18 patients treated with stem-cell transplantation (SCT) (autologous SCT in 15 and allogeneic SCT in three) for hematologic malignancies and compared them with 18 healthy controls. No patient had chronic graft-versus-host disease. We found no difference in glomerular filtration rate estimated from cystatin C (105 vs 111 ml/min/1.73 m(2), p = 0.28). Patients had higher albumin excretion (0.8 vs 0.4 mg/mmol, p = 0.001), but no patient had overt albuminuria (>200 mg/L). Patients had higher diastolic blood pressure (74 vs 67 mmHg, p = 0.003). Two patients (11%) had hypertension. Patients had lower tubular reabsorption of phosphate (0.78 vs 0.91 mmol/L, p = 0.014) and higher excretion of alpha-1-microglobulin (AMG/urine creatinine, 0.4 vs 0.25 mg/mmol, p = 0.038), which correlated with time after SCT (r = 0.6, p = 0.01). We found no difference in fractional excretion (FE) of other electrolytes, amino acid excretion, or urine osmolality. We conclude that renal function was relatively well preserved at a median follow-up of 18 years after childhood SCT. The higher albumin excretion in our patients is of concern, as is the association between excretion of AMG and time after SCT, suggesting that both glomerular and tubular function may deteriorate further.
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PMID:Glomerular and tubular function in young adults treated with stem-cell transplantation in childhood. 2037 2

In most patients with hypertensive nephropathy and low glomerular filtration rate (GFR), the kidney function progressively declines despite the adequate control of the hypertension with angiotensin-converting enzyme inhibition. Previously we found that 2 years of oral sodium citrate slowed GFR decline in patients whose estimated GFR (eGFR) was very low (mean 33 ml/min). This treatment also slowed GFR decline in an animal model of surgically reduced nephron mass. Here, we tested if daily oral sodium bicarbonate slowed GFR decline in patients with hypertensive nephropathy with reduced but relatively preserved eGFR (mean 75 ml/min) in a 5-year, prospective, randomized, placebo-controlled, and blinded interventional study. Patients matched for age, ethnicity, albuminuria, and eGFR received daily placebo or equimolar sodium chloride or bicarbonate while maintaining antihypertensive regimens (including angiotensin-converting enzyme inhibition) aiming for their recommended blood pressure targets. After 5 years, the rate of eGFR decline, estimated using plasma cystatin C, was slower and eGFR was higher in patients given sodium bicarbonate than in those given placebo or sodium chloride. Thus, our study shows that in hypertensive nephropathy, daily sodium bicarbonate is an effective kidney protective adjunct to blood pressure control along with angiotensin-converting enzyme inhibition.
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PMID:Daily oral sodium bicarbonate preserves glomerular filtration rate by slowing its decline in early hypertensive nephropathy. 2087 74

Many uncontrolled studies and a subsequent meta-analysis suggest that hemolytic uremic syndrome (HUS) with a positive history for diarrhea is associated with a significant increase in chronic renal disease. Two recent controlled studies that followed children with this type of HUS after Escherichia coli O157:H7 outbreaks, and where the controls were selected from a group exposed in the outbreak, gave conflicting results. To clarify this apparent difference, we retrospectively compared a cohort of 30 children with sporadic diarrhea-positive HUS with 30 healthy controls who had no history of bloody diarrhea or HUS and who had similar age and gender. Significantly more children with previous HUS than the controls had albuminuria over a median follow-up of 6.2 years. Of these albuminuric patients, one-third had macroalbuminuria compared with none of the controls. Following HUS, children were three times more prone to hypertension and prehypertension, although the difference was not statistically significant. Glomerular filtration rates, estimated by cystatin C, were significantly lower by 30 ml/min/1.73 m(2). Thus, children with sporadic HUS with positive history of diarrhea compared with unexposed controls had a higher prevalence of chronic renal disease; results consistent with the meta-analysis. Prospective studies with appropriate controls are needed to completely resolve this issue.
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PMID:Chronic renal disease is more prevalent in patients with hemolytic uremic syndrome who had a positive history of diarrhea. 2167 38

The value of neutrophil gelatinase-associated lipocalin (NGAL) as a novel marker for early detection of acute renal failure has been highlighted recently. The aim of this study was to assess whether serum NGAL correlated with kidney function in heart allograft recipients. We evaluated serum NGAL, creatinine, and estimated glomerular filtration rate (GFR) in 164 heart allograft recipients on triple therapy. Heart transplant recipients showed significantly higher NGAL values than the control group. Kidney function was estimated using CKD-EPI, Modification of Diet in Renal Disease (MDRD), Cockcroft-Gault formula, 24-hour creatinine clearance, and serum creatinine. Kidney function was significantly impaired among heart transplant recipients compared with healthy volunteers. On univariate analysis serum NGAL strongly correlated with serum creatinine (r = .70, P < .001), estimated GFR (CKD-EPI, r = -.57, P < .001, MDRD r = .56, P < .001, Cockcroft-Gault, r = -.56, P < .001), 24-hour creatinine clearance (r = .43, P < .001), and cystatin C (r = .74, P < .001). In contrast, it was moderately correlated with red blood cell count (r = -.39, P < .01), hemoglobin level (r = -.42, P < .01), NT-proBNP (r = .25, P < .01), and only weakly with New York Heart Association class (r = .21, P < .05), time after transplantation (r = .21, P < .05), or age (r = .19, P < .05) upon multiple regression analysis, the best predictor of serum NGAL was estimated GFR (beta -0.87, P < .0001), explaining 89% of the NGAL concentrations. Even a successful heart transplantation is associated with kidney injury as reflected by elevated serum NGAL and reduced estimated GFR. Therefore, NGAL needs to be investigated as a potential early marker for impaired kidney function/injury, especially among patients with risk factors for renal damage, i.e., hypertension or diabetes, other than heart pathology.
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PMID:Serum neutrophil gelatinase-associated lipocalin correlates with kidney function in heart allograft recipients. 2062 May 26

Heart failure is one of the most common, costly, disabling and deadly diseases. During the last decade, several different indices reflecting renal function such as creatinine-based glomerular filtration rate, circulating levels of cystatin C and low-grade albuminuria have been demonstrated to be independent risk factors for heart failure. This review summarizes our current knowledge of the relationship between diminished renal function and the incidence of heart failure in the community, and also in individuals with increased risk of heart failure such as patients with overt cardiovascular disease, hypertension or diabetes. This review will also put forward important areas of future research in this field.
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PMID:Diminished renal function and the incidence of heart failure. 2067 81

Arterial stiffness is an independent cardiovascular risk factor, along with aging, hypertension, and cardiovascular disease. The augmentation index (AIx) and pulse wave velocity (PWV) are early markers of atherosclerotic vascular changes. Arteriography was used to determine systolic and diastolic blood pressure, pulse pressure (PP), AIx, and PWV in 82 male and 64 female renal transplant recipients (mean [SD] age, 45.3 [11.2] years). Cardiovascular risk was assessed using echocardiography and ultrasonography of the carotid arteries. The left ventricular wall thickness, ejection fraction, and stenosis of the carotid arteries were also measured. Fasting serum creatinine, cystatin C, homocysteine, C-reactive protein, immunoreactive parathyroid hormone, lipid, and calcium-phosphorus concentrations were determined. The serum cystatin concentration was 2.1 (0.2) mg/L, and the homocysteine concentration, 15.2 (2.6) micromol/L. After transplantation, body mass index, fat mass, and visceral fat area increased significantly (P < .01). The AIx was increased (AIx > or =10%) in 20% of men and 37% of women, PWV was increased (>10 m/s) in 43% of men and 34% of women, and PP was pathologically high (>12 m/s) in 10% of men and 12% of women. The PWV was significantly related to age (r = 0.52) and ventricular wall thickness (r = 0.46). Pulse pressure, BMI, and systolic and diastolic blood pressure correlated positively but modestly with PWV. There was a significant relationship between AIx80 and systolic (r = 0.42) and diastolic (r = 0.39) blood pressure and PP (r = 0.33). The ejection fraction correlated negatively with PWV and AIx. There was a strong association between carotid artery stenosis, PWV, and AIx80. All patients with PWV greater than 10 m/s demonstrated carotid artery stenosis. In conclusion, arteriography is an objective, noninvasive, and convenient method for early diagnosis and follow-up of atherosclerosis.
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PMID:Arterial stiffness in chronic renal failure and after renal transplantation. 2069 67

End-stage renal disease (ESRD) and chronic kidney disease (CKD) are increasing health problems worldwide. In the US alone, an estimated 26 million people suffer from some form of CKD. In countries such as India and Pakistan, the prevalence of CKD is also rapidly rising. The presence of CKD is associated with increased perioperative morbidity and mortality, even when adjusted for other variables such as hypertension or diabetes. Frequently, CKD is under diagnosed, so patients and physicians are often unaware of the impaired renal function. Renal dysfunction as a predictor of perioperative outcomes is discussed together with therapeutic interventions aimed at the protection of renal function. Better interventions and diagnostic tools, such as cystatin C, are needed to further improve perioperative morbidity and mortality in patients with CKD.
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PMID:Chronic kidney disease: implications for the perioperative period. 2082 Jan 51


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