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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Renal clearance studies were conducted in conscious, chronically catheterized obese and lean Zucker rats to investigate the natriuretic responses to i) acute IV infusion of isotonic NaCl = 5% of total body weight and ii) IV infusion of alpha rat atrial natriuretic peptide (ANP) in a dose of 300 ng/kg/min. In the baseline state, arterial blood pressure (BP) was significantly higher in obese vs lean rats. Absolute values of GFR and sodium excretion were similar but lower in obese vs lean rats when factored for body weight. In the 2 h period during and after NaCl infusion, obese rats showed a greater natriuresis vs lean while BP rose significantly and similarly. ANP infusion was natriuretic in obese rats but had no effect on lean rats. ANP lowered BP in both groups but BP remained higher in obese vs lean rats at all times. These studies show that in the chronic, unstressed preparation the 6-8 month old, female Zucker obese rat has a higher BP vs the 6-8 month old lean Zucker. The short term natriuretic response to either a NaCl load or ANP infusion is greater in obese vs lean Zuckers and the depressor response to ANP is intact in obese Zuckers. Thus the higher BP in this model of obesity is unlikely to be due to either a defective response to ANP or to a defect in the renal response to acute sodium challenge.
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PMID:Short term natriuretic responses in the conscious Zucker obese rat. 183 82

Hyperinsulinemia has been postulated to link obesity and hypertension via the antinatriuretic actions of insulin. The main goal of this study was to quantitate the importance of the direct intrarenal actions of insulin, independent of systemic effects, in altering blood pressure and renal function. This was accomplished by determining the responses to chronic intrarenal insulin infusion in uninephrectomized, chronically instrumented conscious dogs maintained on a 74 meq/day sodium intake. Insulin was infused at rates calculated to raise intrarenal, but not systemic, insulin to levels similar to those observed in obese hypertensive dogs. Intrarenal insulin infusion (0.6 mU.kg-1.min-1) for 7 days caused transient decreases in sodium excretion but no significant changes in potassium excretion. Mean arterial pressure did not change during 7 days of insulin infusion, averaging 93 +/- 4 mmHg during control and 93 +/- 3 mmHg during insulin infusion. Intrarenal insulin caused small increases in GFR but no significant changes in effective renal plasma flow or renal vascular resistance. These results demonstrate that insulin causes transient decreases in sodium excretion, but chronic intrarenal hyperinsulinemia does not elevate blood pressure in normal dogs. Additional factors other than the direct sodium-retaining effects of insulin may be important in raising blood pressure in obesity-associated hypertension.
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PMID:Chronic intrarenal hyperinsulinemia does not cause hypertension. 203 53

For alterations in serum creatinine to reflect changes in GFR, urine creatinine excretion must remain constant. Although serum creatinine is often used to monitor chronic changes in allograft GFR, creatinine excretion has not been systematically investigated in renal transplant recipients. In the present study, creatinine excretion was examined in 100 patients who survived at least 12 months with functioning renal allografts. Overall, there was a progressive decline in creatinine excretion from 1420 +/- 410 mg/24 hr at 3 months to 1240 +/- 394 mg/24 hr at last follow-up, 89 +/- 35 months after transplantation (mean +/- SD). The decline in creatinine excretion was greatest in those who subsequently returned to dialysis (-27.4 +/- 20.2%, P less than .05) compared with those who died (-6.9 +/- 24.1%), or survived with functioning allografts (-3.7 +/- 18.1%). Multivariate analysis demonstrated that age, sex, body weight, obesity, diabetes, and cumulative average daily corticosteroid dose (factors that affect muscle mass) all influenced creatinine excretion. However, early post-transplant clinical parameters failed to predict patients who subsequently had declines in creatinine excretion. Thus, it was not possible to predict patients in whom chronic changes in allograft function would be underestimated by changes in serum creatinine. Although clinically relevant functional alterations can be detected by changes in serum creatinine, additional measures of GFR should be used to complement the serum creatinine and monitor chronic changes in allograft function after renal transplantation.
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PMID:Creatinine excretion after renal transplantation. 267 99

To evaluate the metabolic effects of long-term treatment with recombinant human (rh) GH in short children with chronic renal failure (CRF), annual oral glucose tolerance tests (oGTT) during rhGH therapy for up to 5 y in 53 prepubertal children with CRF on conservative treatment, dialysis, and after renal transplantation were compared with that of 12 age-matched children treated with rhGH for idiopathic short stature. At the start of rhGH treatment, fasting values of glucose, insulin, glycosylated Hb A (HbA1C), triglycerides, cholesterol, glucose, and insulin responses during oGTT were significantly elevated in all patient groups compared with control subjects (p < 0.001). In the total population, fasting and 2-h postprandial glucose concentrations were inversely correlated with GFR and positively with age and methylprednisolone dosage in transplanted patients. Fasting insulin levels were positively correlated with body mass index and inversely with GFR. RhGH treatment was not associated with a change in fasting or stimulated glucose concentrations in any treatment group throughout the observation period. In contrast, serum insulin levels increased during the first treatment year in all groups, resulting in a more marked elevation of integrated insulin levels in transplant (1402 +/- 179 pM) and dialysis (1025 +/- 114 pM) patients compared with conservatively treated patients (829 +/- 94 pM), and control subjects (719 +/- 89 pM) (p < 0.01). Hyperinsulinemia persisted in all treatment groups for up to 5 y of follow-up. In conclusion, age, renal function, and obesity are the major independent predictors of glucose tolerance in children with CRF. Long-term rhGH treatment does not affect glucose tolerance, but aggravates the preexisting hyperinsulinemia in children with end-stage renal disease. In concert with the dyslipidemia of uremia, the rhGH-promoted hyperinsulinemia may contribute to the long-term risk for premature atherosclerosis in patients with childhood onset CRF.
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PMID:Metabolic effects of long-term growth hormone treatment in prepubertal children with chronic renal failure and after kidney transplantation. The German Study Group for Growth Hormone Treatment in Chronic Renal Failure. 947 86

The purpose of this study was to examine the histologic and functional changes that occur in the kidney in the early stages of obesity caused by a high-fat diet. Lean dogs (n = 8) were fed a standard kennel ration, and obese dogs (n = 8) were fed the standard kennel ration plus a supplement of cooked beef fat each day for 7 to 9 wk or 24 wk. Body weights were 58 +/- 5% greater and kidney weights were 31 +/- 7% greater in obese dogs, compared with the average values for lean dogs. Plasma renin activity and insulin concentrations were both 2.3-fold greater in obese dogs, compared with lean dogs. Obesity was associated with a mean arterial pressure increase of 12 +/- 3 mmHg, a 38 +/- 6% greater GFR, and a 61 +/- 7% higher renal plasma flow, compared with lean dogs. The glomerular Bowman's space area was significantly greater (+41 +/- 7%) in dogs fed the high-fat diet, compared with lean animals, mainly because of expansion of Bowman's capsule (+22 +/- 7%). There was also increased mesangial matrix and thickening of the glomerular and tubular basement membranes and the number of dividing cells (proliferating cell nuclear antigen-stained) per glomerulus was 36 +/- 8% greater in obese dogs, compared with lean dogs. There was also a trend for glomerular transforming growth factor-beta1 expression, as estimated by semiquantitative immunohistochemical analysis, to be elevated with the high-fat diet. Therefore, a high-fat diet caused increased arterial pressure, hyperinsulinemia, activation of the renin-angiotensin system, glomerular hyperfiltration, and structural changes in the kidney that may be the precursors of more severe glomerular injury associated with prolonged obesity.
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PMID:Functional and structural changes in the kidney in the early stages of obesity. 1137 44

We investigated the effect of weight reduction on blood pressure, microalbuminuria and renal function in hypertensive patients with obesity for over 12 months. Twenty-five patients with a body mass index (BMI) of over 25 were prescribed low calorie diet (25 kcal/kg). All patients had mild hypertension and microalbuminuria. They were classified into 2 groups after 12 months. Group A consisted of 10 patients who had a weight loss of at least 5%. Group B consisted of 15 patients who did not have any weight loss. The following results were obtained. (1) The percentage of patients with hyperfiltration (GFR; more than 140 ml/min) was 20%. (2) Blood pressure, fasting plasma insulin level, urinary sodium and albumin excretion rate were significantly decreased in Group A. On the other hand, these changes were not observed in Group B. (3) Reduction in mean arterial blood pressure significantly correlated with the fall in body weight. (4) Renal function did not change during the study period in both groups. (5) Urinary albumin excretion rate significantly correlated with weight reduction, decrease in blood pressure and fasting insulin levels. Blood pressure and urinary albumin excretion rate in hypertensive patients with obesity significantly decreased with weight reduction. Probably, weight loss improves insulin resistance and decrease in the plasma insulin level causes a reduction in blood pressure and urinary albumin excretion rate.
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PMID:[Weight reduction improves high blood pressure and microalbuminuria in hypertensive patients with obesity]. 1143 1

The long-term outcome of 20 preterm infants with extremely low birth weight and acute renal failure in the neonatal period was studied retrospectively over an 18-year period. Those with progressive renal disease are compared with those with normal renal function. Current mean age is 7.5+/-4.6 years (range 3.2-18.5 years). Nine patients showed deterioration in renal function (low GFR group). Increasing proteinuria, as determined by random urine protein/creatinine ratio (Up/c), correlated with deterioration in renal function ( r=0.8, P<0.0001). Prominent risk factors for progression were Up/c >0.6 at 1 year of age [100% sensitivity, 75% positive predictive value (PPV), P<0.01], serum creatinine >0.6 mg/dl at 1 year of age (75% sensitivity, 80% PPV, P<0.01), and a tendency to obesity with body mass index >85th percentile (89% sensitivity, PPV 67%, P=0.03). Loss of renal mass and nephrocalcinosis were not prognostic indicators. This report begins to identify important clinical parameters that should lead to closer surveillance and potential treatment interventions for preservation of renal function in a growing population of surviving low birth weight individuals.
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PMID:Long-term follow-up of extremely low birth weight infants with neonatal renal failure. 1283 91

Endothelial dysfunction has been suggested to play an important role in the development of obesity-induced hypertension. Because endothelin release increases in response to endothelial damage, we examined whether endothelin-1 contributes to increased arterial pressure in a model of visceral obesity produced by feeding Sprague-Dawley rats a high-fat (HF) diet (40% fat w/w, n=6) for 12 months. Arterial and venous catheters were implanted for measurement of mean arterial pressure (MAP) and heart rate (HR) 24 hours per day and intravenous infusions. After a 5-day control period, rats were infused with the selective endothelin-1 type A receptor (ET-A) blocker ABT-627 (2.5 mg/kg per day, IV) for 9 days, followed by a recovery period. Rats fed a standard chow (normal fat, or NF, group: n=6) for 12 months were also infused with ET-A blocker and were used as controls. Compared with NF rats, HF rats had higher MAP (113+/-4 versus 98+/-2 mm Hg), increased visceral fat (18.7+/-2.0 versus 10.8+/-1.4 g), and 3.2-fold increase in plasma leptin despite similar total body weight gain. Long-term ET-A blockade markedly reduced MAP in HF (-14+/-3 mm Hg) and NF (-14+/-2 mm Hg), but it had no effect on HR, GFR, or PRA. These results indicate that a long-term HF diet may cause visceral obesity and increased MAP, even in the absence of major changes in total body weight. Endothelin-1 appears to play an important role in the maintenance of arterial pressure in rats fed HF and NF diets, but it does not appear to contribute to increased MAP in this model of diet-induced hypertension.
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PMID:Role of endothelin-1 in blood pressure regulation in a rat model of visceral obesity and hypertension. 1470 64

It is known that, among human patients with sepsis, acute renal failure (ARF) dramatically increases mortality rates to 50 to 80%. However, the pathogenesis of septic ARF is not fully understood. An increase in endotoxin-induced mortality rates for leptin-deficient ob/ob mice was recently demonstrated. In comparison with ob/ob mice, db/db mice, which are deficient in the long isoforms of leptin receptors (Ob/Rb), demonstrate lower mortality rates after exposure to the endotoxin LPS. In db/db mice, mRNA for the short isoforms of leptin receptors is constitutively expressed in the kidney, lung, liver, and macrophages. It is known that plasma leptin levels increase in rodents after exposure to LPS, and this was demonstrated for db/db mice. Because ob/ob and db/db mice are both obese, factors other than obesity must be involved in the increased mortality rates for ob/ob mice. In this study, the hypothesis that the short forms of leptin receptors might offer protection against endotoxin-induced lethality at least in part by providing protection against ARF was examined. Serum leptin levels were significantly increased with LPS treatment in wild-type and db/db mice but not ob/ob mice. GFR decreased significantly 16 h after the homozygous ob/ob mice received intraperitoneal injections of 0.3 mg/kg LPS (0.37 +/- 0.04 ml/min per g kidney versus 0.83 +/- 0.06 ml/min per g kidney, n = 6, P < 0.01); the mean arterial pressure (MAP) remained unchanged. For ob/ob littermates (+/?ob), there was no significant change in either MAP or GFR when the mice were challenged with the same time interval (16 h) and dose of LPS. In contrast to ob/ob mice, there was no significant change in GFR or MAP when homozygous db/db mice or their littermates received injections of an even higher dose of LPS (0.4 mg/kg). Mouse recombinant leptin had no effect on GFR when ob/ob mice received 0.3 mg/kg LPS injections. However, renal function (serum creatinine levels, 0.4 +/- 0.1 mg/dl versus 0.9 +/- 0.1 mg/dl, P < 0.01) and MAP (68 +/- 4 mmHg versus 51 +/- 2 mmHg, n = 6, P < 0.01) were significantly improved with leptin replacement when the ob/ob mice developed hypotensive ARF with a higher dose of LPS (0.5 mg/kg). In summary, the previously reported increased susceptibility to LPS of ob/ob mice, compared with db/db mice, may be attributable at least in part to increased susceptibility to ARF.
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PMID:Role of leptin deficiency in early acute renal failure during endotoxemia in ob/ob mice. 1497 66

The equation developed from the MDRD (Modification of Diet in Renal Disease) study provides more accurate estimate of GFR than other commonly used equations. The aim of this study was to compare prediction of GFR based on MDRD and Cockcrof-Gault (CG) method. The study was performed in 111 patients (mean age 42 +/- 5 years) with chronic renal impairment (Scr = 281 +/- 83 micromol/l). The mean of MDRD was 0.480 +/- 0.345 ml/s/1.73 m2 and that of CG 0.608 +/- 0.336 ml/s/1.73 m2. The difference is highly significant (p < 0.0001). The mean of CG/MDRD ratio was 1.24 +/- 0.17. This ratio was significantly higher (p < 0.01) in obese patients (1.59 +/- 0.14 vs 1.22 +/- 0.09). The CG/MDRD ratio did not show relation to Scr. The results are in keeping with the assumption that the difference between MDRD and CG method cannot be explained by increased tubular secretion of creatinine in residual nephrons. Obesity seems to be on of the factors responsible for the difference between CG and MDRD values.
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PMID:[A new method to estimate glomerular filtration rate based on serum concentration of creatinine, urea and albumin (MDRD, Modification of Diet in Renal Disease)]. 1532 57


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