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S Klahr

Publications and source records attributed to S Klahr.

At least 145 records · Page 8Linked to original sources
PubMed1989

Effects of protein intake on the progression of renal disease.

In summary, protein restriction appears to be of benefit in certain types of renal disease. Studies measuring GFR and using a concomitant control group are necessary to answer this question with certainty, however. The mechanisms by which changes in dietary protein influence the progression of renal insufficiency have not been defined. Further studies are needed to identify those patients and renal diseases that may benefit from dietary restriction of protein. Long-term studies designed to assess carefully the nutritional impact of prolonged periods of protein restriction on individuals with renal insufficiency are also required.

Animals↗
PubMed1989

Role of atrial peptide in the natriuresis and diuresis that follows relief of obstruction in rat.

The present studies demonstrate that endogenous levels of atrial peptide are significantly elevated in the plasma of rats with bilateral ureteral obstruction (BUO) compared with control rats or rats with unilateral ureteral obstruction. The contribution of endogenous atrial peptide to the natriuresis and diuresis that follows release of BUO was examined by the intravenous infusion of heparin with or without the exogenous administration of atrial peptide. Infusion of heparin, which binds atrial peptide and interferes with its biological effect, decreased the natriuresis and diuresis observed after release of BUO. Heparin administration also markedly blunted the natriuresis and diuresis observed after exogenous administration of atrial peptide following release of BUO in rats. In contrast, heparin administration did not decrease the natriuresis and diuresis seen in the experimental kidney after relief of unilateral ureteral obstruction. The finding of increased plasma levels of atrial peptide in rats with bilateral ureteral obstruction together with the decrease in diuresis and natriuresis observed with the administration of heparin after release of BUO in these animals indicate that endogenous levels of atrial peptide contribute to the natriuresis and diuresis that occur after release of BUO in rats.

Animals↗
PubMed1989

Role of dietary lipids and renal eicosanoids on the progression of renal disease.

Alterations in lipid metabolism occur in patients with chronic renal disease and in patients with the nephrotic syndrome and may have a role in the progression of renal disease in such patients. Evidence accumulated over the last few years indicates that increased ingestion of cholesterol accelerates the development of glomerulosclerosis in guinea pigs, rats and rabbits, and in rats with endogenous hyperlipidemia due to the nephrotic syndrome. Lowering the levels of serum lipids ameliorates the progression of renal disease in obese rats, rats with a remnant kidney and rats with the nephrotic syndrome produced by the aminonucleoside of puromycin. Changes in dietary fatty acids also influence the progression of renal disease. Several eicosanoids influence the progression of renal disease in experimental animals. Maneuvers that decrease the production of thromboxane A2 ameliorate renal disease in rats with a remnant kidney and in mice with lupus nephritis. Increasing the production of vasodilatory prostaglandins (PGE2, prostacyclin) seems to have a beneficial role in the progression of renal disease. The mechanisms by which dietary lipids and/or renal eicosanoids affect the progression of renal disease remain to be defined.

Animals↗
PubMed1988

The progression of renal disease.

The diversity of its causes, the unpredictability of its clinical course, and our expanding knowledge of the conditions that may exacerbate or retard its progression suggest that glomerular sclerosis cannot be attributed to a single aberration in glomerular physiology. Nonetheless, the welter of clinical and experimental observations is beginning to yield a pattern. Agents or conditions injurious to glomerular epithelium tend to cause glomerular sclerosis. Agents or conditions that induce short-term or long-term activation of mesangial cells may lead to glomerular sclerosis. Indeed, one contribution of the healthy epithelium may be to serve as a tonic inhibitor of the intraglomerular processes arising from mesangial-cell activation. Long-term activation of the mesangium is associated with the proliferation and infiltration of cells and with the expansion of the mesangial matrix--the antecedents of sclerosis. We anticipate that different diseases associated with glomerular sclerosis will be found to depend to varying extents on these two potential mechanisms of sclerosis. Beyond a certain threshold of glomerular injury, glomerular diseases share an additional factor: the capacity of both intrinsic cells and infiltrating cells to alter the microenvironment of the glomerulus so that sclerosis progresses inexorably long after the disappearance of the initiating insult. Several potential risk factors may contribute to the progression of chronic renal disease. These factors include systemic hypertension, proteinuria, hyperlipidemia, high protein intake, and probably conditions that lead to glomerular hypertrophy. Interventions designed to minimize the potential contribution of these factors to the progression of renal insufficiency may halt or slow the loss of function of the kidney. Clinical trials designed to examine the effects of these factors on the progressive course of renal insufficiency will help to establish their role and relative importance in humans.

Humans↗
PubMed1988

Effects of obstruction on renal functions.

Following ureteral obstruction there is a progressive fall in glomerular filtration rate (GFR) due to a reduction in single nephron glomerular filtration rate (SNGFR) and a reduced number of filtering nephrons. Renal plasma flow also declines after a transient, prostaglandin-dependent increase, due to afferent and efferent arteriolar vasoconstriction. The vasoactive hormones thromboxane A2 and angiotensin II are implicated in the pathogenesis of the vasoconstriction following ureteral obstruction and they also reduce the glomerular ultrafiltration coefficient by causing mesangial contraction. Ureteral obstruction also leads to profound changes in renal tubular cell function. These include altered sodium and water handling resulting in a post-obstructive diuresis and natriuresis and a failure to dilute or concentrate the urine. Potassium and divalent cation exchange is also affected, as is urinary acidification. Furthermore, the response of the tubule to hormones such as antidiuretic hormone and parathyroid hormone is impaired. The pathophysiology of these alterations in renal function is discussed.

Animals↗
PubMed1988

Immunological aspects of acute ureteral obstruction: immune cell infiltrate in the kidney.

Kidneys from rats subjected to bilateral ureteral obstruction (BUO), unilateral ureteral obstruction (UUO) and UUO with subsequent release were analyzed for leukocyte infiltration. A time-dependent influx of leukocytes, predominantly macrophages and suppressor T lymphocytes, occurred in both the cortex and medulla following obstruction, and disappeared with release of the obstruction. Glomerular macrophages declined following obstruction but increased to levels above control following release. The influx of leukocytes following obstruction was paralleled by an increase in thromboxane B2 excretion by the kidney and coincided with a decrease in glomerular filtration rate (GFR). This would suggest that an influx of immune cells is a prominent feature of the acute renal response to ureteral obstruction. These cells may modulate some of the post-obstructive alterations in renal function via the production of vasoactive substances, such as thromboxane A2.

Acute Disease↗
PubMed1988

Effect of heparin on the glomerular structure and function of remnant nephrons.

The development of glomerular structural abnormalities in remnant nephrons, after ablation of renal mass (subtotal nephrectomy), in rats is largely prevented by the daily injection of heparin. To investigate if this protective effect of heparin is due to attenuation of glomerular hyperperfusion, hypertension and hyperfiltration, which develop in remnant nephrons soon after subtotal nephrectomy, we measured various parameters of glomerular hemodynamics at two weeks (Group 1) and four weeks (Group 2) after removal of 1-3/4 of total kidney mass in heparin-treated (Groups 1A and 2A) and untreated (Groups 1B and 2B) Munich-Wistar rats. When compared to normal non-nephrectomized rats (Group 1C), the values for glomerular capillary hydraulic pressure (PGC), glomerular plasma flow rate (QA) and single nephron filtration rate (SNGFR) in remnant nephrons were found to be markedly and similarly elevated in both Groups 1A and 1B, averaging 71 +/- 4 and 73 +/- 4 mm Hg, 229 +/- 41 and 176 +/- 13 nl/min, 58.9 +/- 6.4 and 60.8 +/- 7.8 nl/min, respectively. Thus, glomerular hemodynamic parameters two weeks after subtotal nephrectomy did not differ between untreated and heparin-treated rats. Likewise, heparin treatment did not decrease the values of PGC and SNGFR assessed four weeks after subtotal nephrectomy, with the average values being 65 +/- 2 mm Hg and 83.8 +/- 7.1 nl/min in Group 2A versus 62 +/- 4 mm Hg and 63.7 +/- 6.5 nl/min in Group 2B.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Effect of diet, age and sex on the renal response to immune injury in the rat.

We investigated the effect of three factors, namely dietary protein intake, age and sex, on the susceptibility of the renal glomerulus to the binding of antiglomerular basement membrane antibody (anti-GBM) in the early (heterologous) phase of anti-GBM nephritis, and the consequent reduction in glomerular filtration rate (GFR) as measured by inulin clearance (CIn). The effect of diet was examined in approximately equal to 8 week-old female Munich-Wistar rats fed a 40% high (HP) or a 6% low (LP) protein diet, and that of sex and age in male and female rats, 6 week or 10 month old. Following an intravenous dose (3 to 20 micrograms/g body wt) of radiolabeled nephritogenic anti-GBM, assessment of glomerular function was followed by quantitation of anti-GBM binding (values corrected for GBM surface area) in isolated glomeruli. At a given plasma level of antibody, the degree of binding of anti-GBM was slightly but significantly higher in HP than LP-fed rats; the decrease in GFR was significantly more pronounced in HP than LP-fed animals. The amount of anti-GBM binding was significantly greater in adult than young animals; however, the consequent decrease in GFR was more pronounced in the young than adult animals. Sex dependency was not discernible in anti-GBM binding or reduction in GFR. In all of the above experimental groups, the degree of anti-GBM binding was closely correlated with the plasma level of anti-GBM, but not with effective renal plasma flow rate, measured by PAH clearance. Separate groups of rats were subjected to experimental manipulation of single nephron GFR, glomerular capillary hydraulic pressure and glomerular plasma flow rate, by partial aortic constriction and saralasin administration. This set of experiments, using a tracer amount of non-nephritogenic anti-GBM, revealed that glomerular anti-GBM binding is independent of any of the above parameters. The studies indicate that dietary protein intake and age, but not sex, are among the factors determining the susceptibility of the glomerulus to acute immune injury. Since the binding of anti-GBM is determined by the affinity property of the glomerulus per se, and not by the prevailing hemodynamic pattern, the observed dependence of susceptibility to functional impairment on age and protein intake appears to also reflect a property of the glomerulus, which is influenced by age and the degree of dietary protein intake.

Aging↗
PubMed1988

N-desulfated/acetylated heparin ameliorates the progression of renal disease in rats with subtotal renal ablation.

The effect of administration of N-desulfated/acetylated heparin, almost completely devoid of anticoagulant activity, on the progression of renal disease was examined in rats with 13/4 nephrectomy. Three groups of rats with 13/4 nephrectomy were studied. Group I (control, n = 11) received 0.15 ml of 0.15 M NaCl subcutaneously twice daily for 5 wk; group 2 (n = 11) received 0.15 ml twice daily of N-desulfated/acetylated heparin (5.4 mg/ml; less than 0.5 U/ml); group 3 (n = 9) received 0.15 ml twice daily of standard beef lung heparin (5.4 mg/ml; 977 U/ml). Clearances and renal histological studies were done at the end of 5 wk of heparin or saline administration. Rats given the heparin preparations had significantly higher inulin clearances (2.55 +/- 0.38 ml/min per body weight (BW) for group 2, or 2.60 +/- 0.24 ml/min per kg BW for group 3) than control rats (1.59 +/- 0.20 ml/min per kg BW). Histological analysis revealed a greater number of glomeruli with segmental or global sclerosis, hyalinosis, or fibrosis (36.6%) in control rats than in rats receiving N-desulfated/acetylated heparin (6.2%) or standard heparin (3.0%). Blood pressure averaged 169.4 +/- 6.2 mmHg in controls, 119.1 +/- 6.1 in rats of group 2, and 124.3 +/- 2.5 in rats of group 3. The values for blood pressure were significantly lower in the two groups receiving heparin than in controls. These studies indicate that a heparin preparation, almost completely devoid of anticoagulant properties, affords the same degree of protection against progression of renal disease as does standard heparin in rats with subtotal renal ablation. It is suggested that other biological properties of heparin may be responsible for the effects observed.

Acetylation↗
PubMed1987

Renal infection in autosomal dominant polycystic kidney disease.

Upper urinary tract (renal) infections have been reported to be frequent and difficult to treat in patients with autosomal dominant polycystic kidney disease. This study examined renal infections and responses to therapy in this patient population. Fifteen cyst infections and 11 parenchymal infections occurred during the study. Eighty-seven percent of the cyst and 91 percent of the parenchymal infections occurred in women. Gram-negative enterics were the causative organisms in 92 percent of the cyst and 100 percent of the parenchymal infections. All of the parenchymal but only one of the cyst infections responded to therapy with ampicillin and an aminoglycoside despite favorable sensitivities. Eighty-three percent of the cyst infections were eradicated with use of lipid-soluble antibiotics. It is concluded that Cyst infections are refractory to therapy with the antibiotics commonly used to treat urinary infections; Female preference and enteric organism predominance suggest that these renal infections are acquired retrograde from the urinary bladder.

Adult↗
PubMed1987

Effect of dietary lipids on renal function in rats with subtotal nephrectomy.

Female rats with 1-3/4 nephrectomy were divided in two groups and pair fed for five weeks diets differing in their linoleic acid content. Five weeks after subtotal nephrectomy, values for glomerular filtration rate and renal plasma flow were significantly higher and the values of blood pressure significantly lower in rats fed a diet rich in linoleic acid. Systolic blood pressure averaged 156 +/- 5.6 mm Hg in high and 215 +/- 8.1 mm Hg in low linoleic acid-fed rats. Differences in the values of blood pressure between the two groups were observed three weeks after subtotal renal ablation and persisted throughout the period of observation. Inulin clearance averaged 0.89 +/- 0.07 ml/min in the high and 0.44 +/- 0.05 ml/min in the low linoleic acid group. Protein excretion in the urine was significantly less in rats fed the high linoleic acid diet (36.9 +/- 4.4 mg/24 hr) than in those fed the low linoleic acid diet (90.1 +/- 12.5 mg/24 hr). The weight of the remnant kidney five weeks after subtotal renal ablation was greater in rats fed a low linoleic acid diet as compared to those fed a high linoleic acid diet (P less than 0.05). Glomerular lesions were more severe in rats fed a low linoleic acid diet than in those fed a high linoleic acid diet. Feeding high linoleic acid diets to normal and subtotally nephrectomized rats increased the content of linoleic and arachidonic acid in renal cortex and medulla.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Exercise training ameliorates progressive renal disease in rats with subtotal nephrectomy.

To determine the effect of chronic exercise training on renal function in animals with moderate renal insufficiency, rats with 75% renal ablation were either exercise trained by swimming for two months or remained sedentary. Glomerular filtration rate was significantly higher in trained (1.89 +/- 0.07 ml/min) than in sedentary rats (1.52 +/- 0.11 ml/min). No change was observed in renal blood flow or the degree of hypertension. Proteinuria was reduced in trained (13.6 +/- 4.9 mg/24 hr) compared to sedentary animals (33.5 +/- 9.2 mg/24 hr). The degree of glomerulosclerosis was much less prominent in trained animals. Plasma, low-density lipoprotein cholesterol-levels and total triglycerides were reduced in trained compared to sedentary rats. This study suggests that chronic exercise training ameliorates the progression of renal disease and improves plasma lipids in rats with moderate renal insufficiency. The mechanism for this improvement in renal function appears to be independent of the influence of systemic blood pressure.

Animals↗
PubMed1987

Glucose metabolism in muscle of sedentary and exercised rats with azotemia.

Insulin resistance has been demonstrated in chronic renal failure patients and may be improved by exercise training, but the mechanisms have not been identified. In this study, the response of glucose uptake, glycogen synthesis, and glucose utilization via glycolysis (glycolytic utilization) to stimulation by insulin and/or acute exercise were determined in isolated muscles from rats with moderate renal insufficiency that were exercise trained or remained sedentary. Moderate renal insufficiency had no effect on the basal rate, insulin sensitivity, or insulin responsiveness of glucose uptake, glycogen synthesis, or glycolytic utilization in muscle. The enhanced insulin responsiveness of both glycogen synthesis and glucose uptake following acute exercise, noted in control animals, was less in rats with moderate renal insufficiency, but the enhanced basal rate and insulin sensitivity after exercise were unaffected by moderate renal insufficiency. Exercise training increased the insulin sensitivity and responsiveness of muscle glucose uptake and glycolytic utilization in rats with moderate renal insufficiency and in controls. The effects of acute exercise and exercise training on insulin responsiveness of glucose uptake were additive in controls but not in animals with moderate renal insufficiency. These findings are compatible with the concept that moderate renal insufficiency is associated with a postreceptor defect in insulin's action in muscle, detectable only following maximal stimulation of glucose transport by insulin and exercise, and partially correctable by exercise training.

Animals↗
PubMed1987

Insulin-stimulated protein metabolism in chronic azotemia and exercise.

To determine whether training reduces the acute catabolic stress of an exercise bout, control and azotemic rats, either exercise trained or untrained, were subjected to a bout of exercise or allowed to rest. Protein turnover was measured immediately following exercise in isolated muscles. Azotemia (no exercise) increased protein degradation; acute exercise (no azotemia) decreased protein synthesis. Protein catabolism was greatest in acutely exercised azotemic rats. Training reduced azotemia-induced and acute exercise-stimulated increase in protein degradation. To determine whether this improvement in protein metabolism by training was due to increased insulin sensitivity, the dose-response to insulin was determined. Resistance of protein synthesis or degradation to insulin was not observed in azotemic rats. Either acute exercise or training increased sensitivities of protein degradation and synthesis to insulin; training also increased responsiveness of protein degradation to insulin. Thus exercise training reduced the elevated muscle protein catabolism due to azotemia and/or acute exercise and enhanced the action of insulin on muscle.

Acute Kidney Injury↗
PubMed1987

Quantitation of proteinuria by the use of protein-to-creatinine ratios in single urine samples.

Measurements of protein-to-creatinine ratios in single-voided urine samples were compared with 24-hour urinary protein excretions for quantitation of proteinuria in inpatients and outpatients. Patients included those representing a broad spectrum of renal diseases, a wide range of proteinuria, and various degrees of reduction in glomerular filtration rate. Protein-to-creatinine ratios in single-voided urine samples correlated well with measurements of 24-hour urinary protein. This simple single-voided test is reliable and useful in the screening, assessment, and follow-up of proteinuria and avoids the problems associated with 24-hour urine collection.

Adolescent↗