GFR increases before renal mass or ODC activity increase in rats fed high protein diets

GFR increases before renal mass or ODC activity increase in rats fed high protein diets. Consumption of a high protein diet causes renal hypertrophy and increased glomerular filtration rate (GFR). To determine the relationship between increases in GFR, renal ornithine decarboxylase activity (ODC), arginase activity, and renal growth, dietary protein intake was increased from 8.5% to 40% in 50 male Sprague-Dawley rats (HP). Forty-one rats remained on 8.5% protein as time controls (LP). Eight to 17 animals were killed daily for measurement of kidney weight (kidney wt), ODC and arginase activities, total kidney protein and DNA content. GFR increased within the first 24 hours after the increase in dietary protein and reached a maximum within 48hrs. ODC increased from 9.7 ± 0.8 U/g to a peak of 170 ± 35 U/g at 48 hours, decreasing to a stable value of 28.6 ± 8.0 U/g at 72 hours and 25.4 ± 5.1 U/g at 168 hours, a value significantly greater than that at time zero. Arginase activity did not change. Kidney wt as percent body weight (body wt) increased after the initial increase in both GFR and in ODC activity. The peak in ODC activity corresponded with the maximum increase in GFR and preceded the increase in renal mass. After GFR stabilized, ODC activity decreased to a plateau and renal growth relative to body wt ceased. The increase in kidney weight was accompanied by a parallel increase in total kidney protein. Kidney protein/ kidney DNA ratio increased significantly by 96 hours, indicating that renal hypertrophy had occurred. The sequence of these events suggests that increasing GFR may trigger the rise in ODC activity

Estrogen effects on triglyceride metabolism in analbuminemic rats

Estrogen effects on triglyceride metabolism in analbuminemic rats.BackgroundTriglyceride (TG) levels are normally lower in female rats, while the opposite is the case in the Nagase analbuminemic rats (NAR). Increased TG levels in normal males are caused by a testosterone-mediated decrease in postheparin (PH) lipoprotein lipase (LpL). Castration of males reduces TG, while castration of females is without effect. TG levels are reduced by castration of the female NAR, suggesting that estrogen rather than testosterone causes hypertriglyceridemia in this strain. The mechanism for this increase is unknown.MethodsWe measured secretion of very-low density lipoprotein (VLDL) TG using Triton WR 1339 clearance as the disappearance from blood of 3H-trioleate and 14C-cholesterol–labeled chylomicrons (CM), and the activity of the PH lipases: LpL and hepatic lipase (HL). All were determined in Sprague-Dawley (SD) and NAR female, male, and ovariectomized (OVX) rats.ResultsTG levels were significantly greater in female NAR in comparison to all other groups. Ovariectomy of NAR significantly ameliorated hypertriglyceridemia. VLDL TG secretion was significantly greater in intact female NAR compared with all other groups. There were no other differences in VLDL TG secretion among the other groups. The clearance of CM was greatest in female SD rats, and OVX had no effect. NAR cleared CM less well than did SD rats (P < 0.001), but among NAR, clearance was greatest in OVX NAR and male NAR (P < 0.002). Both PH LpL activity and HL activity were lowest in female NAR (P < 0.05). Ovariectomy partially corrected the defect in HL (P < 0.05).ConclusionTG levels in female NAR are in part a result of increased VLDL-TG secretion, an effect mediated by estrogen. The presence of an estrogen-mediated catabolic defect that was alleviated by OVX was also observed. This catabolic defect is likely a result of an estrogen-mediated decrease both in LpL and HL expressed only in the presence of analbuminemia

The acute-phase response varies with time and predicts serum albumin levels in hemodialysis patients

The acute-phase response varies with time and predicts serum albumin levels in hemodialysis patients.BackgroundCross sectional studies have established that the serum albumin level is dependent on serum levels of acute-phase proteins (APPs) or cytokine levels in hemodialysis patients. While the acute-phase response is generally associated with acute inflammatory events, a cross sectional analysis relating laboratory values to outcomes assumes these values to be unchanging. The longitudinal relationship among laboratory measurements and how they vary over time in a population of patients are unknown.MethodsPatients who were enrolled in the HEMO Study were recruited into an ancillary longitudinal study to establish the predictive effect of temporal variation in the levels of APPs and of temporal variation in normalized protein catabolic rate (nPCR) on the serum albumin concentration. nPCR was measured monthly using a double-pool method. The positive APPs—C-reactive protein (CRP), α1 acid glycoprotein (α1-AG), and ceruloplasmin—and the negative APP—transferrin (Trf)—were measured in serum obtained before each dialysis session for six weeks and then monthly in 37 hemodialysis patients. A random coefficient regression analysis was used to assess the association of serum albumin with other measured parameters at each time point, as well as fixed patient characteristics.ResultsThe within-subject coefficients of variation of albumin (median, range of 25th to 75th percentiles; median, 0.0614; range, 0.0485 to 0.0690) were significantly less than that of APPs (CRP, median, 0.878; range, 0.595 to 1.314, P < 0.05; and α1 AG, median, 0.173; range, 0.116 to 0.247, P < 0.05). The levels of APPs and albumin varied considerably over time. The primary predictor of current albumin was the current CRP level (P = 0.0014). nPCR also was a significant predictor for albumin levels (P = 0.0440) after controlling for the effect of APPs, suggesting an effect of nPCR on serum albumin concentration irrespective of the acute-phase response. Age and the presence of an arteriovenous graft were significant predictors that were associated with reduced albumin.ConclusionsThe acute-phase response is intermittent and is not a continuous feature in individual dialysis patients. Levels of APPs are the most powerful predictors for the levels of albumin concentration in hemodialysis in a longitudinal setting. Since variations in albumin are small, measurement of variations in APPs may provide greater insight into the dynamics of clinically relevant processes

The effect of frequent hemodialysis on nutrition and body composition: frequent Hemodialysis Network Trial.

We investigated the effects of frequency of hemodialysis on nutritional status by analyzing the data in the Frequent Hemodialysis Network Trial. We compared changes in albumin, body weight, and composition among 245 patients randomized to six or three times per week in-center hemodialysis (Daily Trial) and 87 patients randomized to six times per week nocturnal or three times per week conventional hemodialysis, performed largely at home (Nocturnal Trial). In the Daily Trial, there were no significant differences between groups in changes in serum albumin or the equilibrated protein catabolic rate by 12 months. There was a significant relative decrease in predialysis body weight of 1.5 ± 0.2 kg in the six times per week group at 1 month, but this significantly rebounded by 1.3 ± 0.5 kg over the remaining 11 months. Extracellular water (ECW) decreased in the six times per week compared with the three per week hemodialysis group. There were no significant between-group differences in phase angle, intracellular water, or body cell mass (BCM). In the Nocturnal Trial, there were no significant between-group differences in any study parameter. Any gain in 'dry' body weight corresponded to increased adiposity rather than muscle mass but was not statistically significant. Thus, frequent in-center hemodialysis reduced ECW but did not increase serum albumin or BCM while frequent nocturnal hemodialysis yielded no net effect on parameters of nutritional status or body composition

Lipid levels are inversely associated with infectious and all-cause mortality: international MONDO study results.

Cardiovascular (CV) events are increased 36-fold in patients with end-stage renal disease. However, randomized controlled trials to lower LDL cholesterol (LDL-C) and serum total cholesterol (TC) have not shown significant mortality improvements. An inverse association of TC and LDL-C with all-cause and CV mortality has been observed in patients on chronic dialysis. Lipoproteins also may protect against infectious diseases. We used data from 37,250 patients in the international Monitoring Dialysis Outcomes (MONDO) database to evaluate the association between lipids and infection-related or CV mortality. The study began on the first day of lipid measurement and continued for up to 4 years. We applied Cox proportional models with time-varying covariates to study associations of LDL-C, HDL cholesterol (HDL-C), and triglycerides (TGs) with all-cause, CV, infectious, and other causes of death. Overall, 6,147 patients died (19.2% from CV, 13.2% from infection, and 67.6% from other causes). After multivariable adjustment, higher LDL-C, HDL-C, and TGs were independently associated with lower all-cause death risk. Neither LDL-C nor TGs were associated with CV death, and HDL-C was associated with lower CV risk. Higher LDL-C and HDL-C were associated with a lower risk of death from infection or other non-CV causes. LDL-C was associated with reduced all-cause and infectious, but not CV mortality, which resulted in the inverse association with all-cause mortality

Estrogen worsens incipient hypertriglyceridemic glomerular injury in the obese Zucker rat

Estrogen worsens incipient hypertriglyceridemic glomerular injury in the obese Zucker rat.BackgroundThe obese Zucker rat (OZR) is a model of glomerulosclerosis and renal failure in the setting of hyperlipidemia, hyperinsulinemia, and obesity. Our prior work in OZRs has shown that ovariectomy attenuates glomerulosclerosis, while added estrogen worsens it. To investigate the mechanism of estrogen's effects on glomerular disease in this model, we evaluated the effects of ovariectomy and estrogen supplementation on seven-week peripubertal OZRs. At this time point, rats exhibit no overt histologic glomerular disease, but are just beginning to show elevated urinary albumin excretion.MethodsFemale OZRs fed ad libitum were ovariectomized at four weeks, with or without estrogen supplementation to raise estrogen levels to just below those of preoestral adults (mean 16.5 pg/mL). Sham-operated controls were included.ResultsOvariectomy normalized albuminuria, lowered total and very low-density lipoprotein triglycerides, and reduced glomerular fibronectin expression. Estrogen supplementation worsened albuminuria and raised total/very low-density lipoprotein triglycerides and total cholesterol. Estrogen-supplemented rats exhibited enhanced glomerular deposition of apo A-IV and apo B, increased glomerular expression of desmin and type IV collagen, and increased interstitial macrophage deposition.ConclusionEstrogen may be permissive for the early development of renal disease in OZRs and may act by increasing triglyceride-rich lipoproteins, which then bind to glomerular cells and initiate or accelerate glomerulosclerosis

Effect of frequent hemodialysis on residual kidney function.

Frequent hemodialysis can alter volume status, blood pressure, and the concentration of osmotically active solutes, each of which might affect residual kidney function (RKF). In the Frequent Hemodialysis Network Daily and Nocturnal Trials, we examined the effects of assignment to six compared with three-times-per-week hemodialysis on follow-up RKF. In both trials, baseline RKF was inversely correlated with number of years since onset of ESRD. In the Nocturnal Trial, 63 participants had non-zero RKF at baseline (mean urine volume 0.76 liter/day, urea clearance 2.3 ml/min, and creatinine clearance 4.7 ml/min). In those assigned to frequent nocturnal dialysis, these indices were all significantly lower at month 4 and were mostly so at month 12 compared with controls. In the frequent dialysis group, urine volume had declined to zero in 52% and 67% of patients at months 4 and 12, respectively, compared with 18% and 36% in controls. In the Daily Trial, 83 patients had non-zero RKF at baseline (mean urine volume 0.43 liter/day, urea clearance 1.2 ml/min, and creatinine clearance 2.7 ml/min). Here, treatment assignment did not significantly influence follow-up levels of the measured indices, although the range in baseline RKF was narrower, potentially limiting power to detect differences. Thus, frequent nocturnal hemodialysis appears to promote a more rapid loss of RKF, the mechanism of which remains to be determined. Whether RKF also declines with frequent daily treatment could not be determined

Apolipoprotein L1 gene variants associate with prevalent kidney but not prevalent cardiovascular disease in the Systolic Blood Pressure Intervention Trial.

Apolipoprotein L1 gene (APOL1) G1 and G2 coding variants are strongly associated with chronic kidney disease (CKD) in African Americans (AAs). Here APOL1 association was tested with baseline estimated glomerular filtration rate (eGFR), urine albumin:creatinine ratio (UACR), and prevalent cardiovascular disease (CVD) in 2571 AAs from the Systolic Blood Pressure Intervention Trial (SPRINT), a trial assessing effects of systolic blood pressure reduction on renal and CVD outcomes. Logistic regression models that adjusted for potentially important confounders tested for association between APOL1 risk variants and baseline clinical CVD (myocardial infarction, coronary, or carotid artery revascularization) and CKD (eGFR under 60 ml/min per 1.73 m(2) and/or UACR over 30 mg/g). AA SPRINT participants were 45.3% female with a mean (median) age of 64.3 (63) years, mean arterial pressure 100.7 (100) mm Hg, eGFR 76.3 (77.1) ml/min per 1.73 m(2), and UACR 49.9 (9.2) mg/g, and 8.2% had clinical CVD. APOL1 (recessive inheritance) was positively associated with CKD (odds ratio 1.37, 95% confidence interval 1.08-1.73) and log UACR estimated slope (β) 0.33) and negatively associated with eGFR (β -3.58), all significant. APOL1 risk variants were not significantly associated with prevalent CVD (1.02, 0.82-1.27). Thus, SPRINT data show that APOL1 risk variants are associated with mild CKD but not with prevalent CVD in AAs with a UACR under 1000 mg/g

Etiology of the Protein-Energy Wasting Syndrome in Chronic Kidney Disease: A Consensus Statement From the International Society of Renal Nutrition andMetabolism (ISRNM)

Protein-energy wasting (PEW), a term proposed by the International Society of Renal Nutrition and Metabolism (ISRNM), refers to the multiple nutritional and catabolic alterations that occur in chronic kidney disease (CKD) and associate with morbidity and mortality. To increase awareness, identify research needs, and provide the basis for future work to understand therapies and consequences of PEW, ISRNM provides this consensus statement of current knowledge on the etiology of PEW syndrome in CKD. Although insufficient food intake (true undernutrition) due to poor appetite and dietary restrictions contribute, other highly prevalent factors are required for the full syndrome to develop. These include uremia-induced alterations such as increased energy expenditure, persistent inflammation, acidosis, and multiple endocrine disorders that render a state of hypermetabolism leading to excess catabolism of muscle and fat. in addition, comorbid conditions associated with CKD, poor physical activity, frailty, and the dialysis procedure per se further contribute to PEW. Published by Elsevier Inc. on behalf of the National Kidney Foundation, Inc.Abbott NutritionShireAbbot Renal NutritionBaxter HealthcareKarolinska Inst, Div Renal Med, Dept Clin Sci Intervent & Technol, Solna, SwedenUniversidade Federal de São Paulo, Div Nephrol, Dept Med, São Paulo, BrazilVanderbilt Univ, Sch Med, Dept Med, Div Nephrol, Nashville, TN 37212 USAUniv Calif Irvine, Med Ctr, Harold Simmons Ctr, Div Nephrol & Hypertens, Orange, CA USAUniv Calif Davis, Dept Internal Med, Davis, CA 95616 USAUniv Calif Davis, Dept Biochem & Mol Med, Davis, CA 95616 USABaylor Coll Med, Dept Med, Div Nephrol, Houston, TX 77030 USAEmory Univ, Sch Med, Div Renal, Dept Med, Atlanta, GA 30306 USAAtlanta Dept Vet Affairs Med Ctr, Res Serv, Decatur, GA 30033 USAUniv Wurzburg, Div Nephrol, Dept Internal Med, D-97070 Wurzburg, GermanyUniv Hong Kong, Dept Med, Queen Mary Hosp, Hong Kong, Hong Kong, Peoples R ChinaVrije Univ Amsterdam Med Ctr, Dept Nephrol, Amsterdam, NetherlandsUniversidade Federal de São Paulo, Div Nephrol, Dept Med, São Paulo, BrazilWeb of Scienc