Biomedical subjects

A Parbtani

Publications and source records attributed to A Parbtani.

At least 19 recordsLinked to original sources

PubMed2003

Increased expression of insulin-like growth factors in progressive glomerulonephritis of the MRL/lpr mouse.

Glomerulonephritis is an important complication of systemic lupus erythematosus (SLE). The tissue distribution and exact role of the insulin-like growth factors (IGFs) in the development of lupus nephritis in the MRL/lpr mouse model have not been established. The present study was undertaken to evaluate the changes over time in mRNA and peptide expression of IGF-I and IGFBP-2 in the MRL/lpr mouse. Using in situ hybridization and immunocytochemistry techniques, the expression of IGF-I and IGFBP-2 in MRL/lpr mouse was examined and compared to their congenic normal MRL-++ mouse counterparts from nine to 24 weeks of age. In the MRL-++ and MRL/lpr mouse kidneys, IGF-I and IGFBP-2 mRNA expression was limited to the cortical and medullary collecting ducts, while their immunoreactivity (IR) was localized to the cortical and medullary collecting ducts, loop of Henle, glomeruli and proximal tubules. Over time, and with progression of disease, the MRL/lpr mice displayed a significant increase in IGF-I IR and a modest increase in IGFBP-2 IR within the outer cortical glomeruli, which was associated with a significant increase in glomerulosclerosis and glomerular cell proliferation and with a significant decrease in renal function. In conclusion, this overexpression of IGF-I and IGFBP-2 within the glomeruli of the MRL/lpr mouse kidney supports their potential role in the alterations in renal function and morphology that accompany lupus nephritis.

Animals↗

PubMed2001

Flaxseed in lupus nephritis: a two-year nonplacebo-controlled crossover study.

OBJECTIVE: The objective of this study was to determine the renoprotective effects of ground flaxseed in patients with lupus nephritis. METHODS: Forty patients with lupus nephritis were asked to participate in a randomized crossover trial of flaxseed. Twenty-three agreed and were randomized to receive 30 grams of ground flaxseed daily or control (no placebo) for one year, followed by a twelve-week washout period and the reverse treatment for one year. At baseline and six month intervals, serum phospholipids, flaxseed sachet counts, serum creatinine, 12-hour urine albumin excretion and urine albumin to creatinine ratios, serum viscosity and plasma lipids were measured. RESULTS: There were eight drop-outs and of the 15 remaining subjects flaxseed sachet count and serum phospholipid levels indicated only nine were adherent to the flaxseed diet. Plasma lipids and serum viscosity were unaltered by the flaxseed supplementation whereas serum creatinine in the compliant patients during flaxseed administration declined from a mean of 0.97+/-0.31 mg/dL to a mean of 0.94+/-0.30 mg/dL and rose in the control phase to a mean of 1.03+/-0.28 mg/dL [p value <0.08]. Of the fifteen patients who completed the study, similar changes were noted [p value <0.1]. The nine compliant patients had lower serum creatinines at the end of the two-year study than the 17 patients who refused to participate [p<0.05]. Microalbumin at baseline declined in both control and flaxseed time periods, but there was a trend for a greater decline during flaxseed administration [p<0.2]. CONCLUSIONS: Flaxseed appears to be renoprotective in lupus nephritis, but this interpretation is affected by under powering due to poor adherence and potential Hawthorne effects.

Albuminuria↗

PubMed2000

A novel treatment for lupus nephritis: lignan precursor derived from flax.

BACKGROUND: Flaxseed has renoprotective effects in animal and human lupus nephritis. We have recently extracted the lignan precursor (secoisolariresinol diglucoside) (SDG) to determine if this more palatable derivative of flaxseed would exert renoprotection similar to the whole flaxseed in the aggressive MRL/lpr lupus mouse model. METHODS: 131 MRL/lpr mice were randomly assigned to saline gavage, 600, 1,200 and 4,800 microg lignan gavage groups. At 7 weeks, 6 animals underwent platelet aggregating factor (PAF) lethal challenge and 40 were studied with urine collection to determine the levels of secoisolariresinol, enterodiol and enterolactone in the gavaged animals. A baseline study of 10 saline gavaged animals took place at 6 weeks. 25 animals in the saline gavage, 600 and 1200 microg lignan groups were studied at 14 and 22 weeks for GFR, spleen lymphocyte S-phase and organ weight studies. RESULTS: Metabolic studies indicated that secoisolariresinol is the major metabolite absorbed and the lowest lignan dose provides a lengthening in survival for the PAF lethal challenge. Body weight, fluid and water intake studies demonstrated that the lignan was well tolerated. Changes in proteinuria, GFR and renal size showed a time- and dose-dependent protection for the lignan precursor. Cervical lymph node size and spleen lymphocyte cells in the S-phase demonstrated modest dose-dependent reductions in the lignan gavaged groups. CONCLUSION: SDG was converted in the gut to secoisolariresinol, which was absorbed and well tolerated by the MRL/lpr mice. Renoprotection was evidenced, in a dose-dependent fashion, by a significant delay in the onset of proteinuria with preservation in GFR and renal size. This study suggests that SDG may have a therapeutic role in lupus nephritis.

4-Butyrolactone↗

PubMed1998

Effects of two low-flux cellulose acetate dialysers on plasma lipids and lipoproteins--a cross-over trial.

BACKGROUND: Studies have shown a beneficial effect of high-flux dialysis on lipids, lipoproteins and lipoprotein lipase (Lpl) activity. This has been attributed to improved clearance of Lpl-inhibitory molecules of middle molecular weight, but differences in flux or biocompatibility have not been addressed. We conducted a blinded cross-over trial of two cellulose acetate dialysers (AN140, Althin Medical Inc. and CA210, Baxter Inc.) of similar flux (11 ml/h/mmHg transmembrane pressure) but with different clearances of larger molecules [AN140 sieving coefficient at mol. wt 11,000 Da (beta2-microglobulin) 0.6; CA210 sieving coefficient negligible]. METHODS: Sixteen patients were divided into two groups to receive dialysis with AN140 for 1 week followed by CA210 or vice versa. Before and after the third dialysis with each membrane, plasma lipid and lipoprotein concentrations were measured. Post-dialysis post-heparin lipase activity was measured in six patients. RESULTS: Fifteen patients completed the study. No difference between dialysers was found for apolipoprotein (apo) A1, B or total cholesterol measurements. The rise in triglyceride post-dialysis was attenuated by AN140 (rise 0.05 +/- 0.4 mmol/l vs CA210 0.44 +/- 0.54 mmol/l, P=0.03), while high density lipoprotein (HDL) cholesterol was increased by AN140 (rise 0.18 +/- 0.12 mmol/l vs CA210 0.06 +/- 0.14 mmol/l, P<0.02). ApoE rose with AN140 during dialysis but declined with CA210 (1.10 +/- 1.06 mg/dl and -0.77 +/- 0.63 mg/dl, P=0.002) as did apoCIII (HDL) (AN140 rise 1.33 +/- 2.06 mg/dl; CA210 fall -0.67 +/- 0.73 mg/dl, P=0.001). Lpl activity, measured in six patients, tended to be higher for AN140 (45.3 +/- 10.5 mmol FFA/ml plasma/h vs CA210 (37.2 +/- 7.9 mmol FFA/ml plasma/h) (P=0.16). CONCLUSIONS: We conclude that low-flux dialysis using a cellulose acetate membrane with good clearance of higher molecular weight molecules may be associated with beneficial changes in plasma lipids and lipoproteins.

Adult↗

PubMed1996

Acute hemodynamic and neurohoromonal effects of furosemide in critically ill pediatrics patients.

OBJECTIVES: To study the acute hemodynamic effects of furosemide in critically ill pediatrics patients, the temporal relationship between hemodynamic changes and changes in neuroendocrine axis, and the temporal relationship between hemodynamic changes and urine output. DESIGN: Prospective study. SETTING: Pediatric intensive care unit in a tertiary care university center. PATIENTS: Fourteen critically ill pediatric patients who clinically required diuretic therapy. INTERVENTIONS: Before and after furosemide administration, hemodynamic and neurohormonal measurements were taken. MEASUREMENTS AND MAIN RESULTS: Hemodynamic and neurohormonal responses to acute diuretic therapy were measured in 14 pediatric patients treated with furosemide (1 mg/kg/dose). Cardiac index deteriorated by 10 mins after drug administration (-9.4+/-3.9%, p<.05) and was associated with an increase in systemic vascular resistance (17.1+/-4.8%, p<.05). There was a subsequent increase in cardiac index (20+/-4.9%, p<.05) at 30 mins, with a decrease in systemic vascular resistance (-11.5+/-5.2%, p<.05). These hemodynamic changes were associated with marked increases in renin and norepinephrine concentrations and an increase in urinary prostaglandin release. The hemodynamic and neurohormonal effects had their onset before maximum diuresis. CONCLUSION: Intravenous furosemide administration in acutely ill pediatric patients results in an acute but transient deterioration in cardiac function that appears to parallel the neuroendocrine changes rather than the acute diuresis.

Adolescent↗

PubMed1996

Dietary alteration of dihomogamma-linolenic acid/arachidonic acid ratio in a rat 5/6-renal-ablation model. The Nutrition & Kidney Disease Research Group.

Interest in the modulation of renal diseases by polyunsaturated fatty acids (PUFA) led this group to examine the effects of borage oil (BO) and corn oil (CO) in the rat 5/6-renal-ablation model. BO is a rich source of gamma-linolenic acid (GLA; 18:3n-6), which is elongated to dihomogamma-linolenic acid (DGLA; 20:3n-6). CO is a rich source of linoleic acid (LA; 18:2n-6), a GLA and arachidonic acid (AA; 20:4n-6) precursor. The purpose of this study was to assess whether an increased DGLA:AA ratio as provided by BO would confer benefits beyond those provided by LA present in corn oil. Forty rats were used for the experiment. Seven rats were used for presurgery measurements. The remaining animals were subjected to 5/6 nephrectomy. Surviving rats (N = 30) were fed regular laboratory diet (RLD) for 7 days, at which time seven rats were used to obtain 1-wk postnephrectomy data. The remainder were then allocated to receive either RLD (N = 8), 15% BO (N = 8), or 15% CO (N = 7) diets for 20 wk. Body weight, renal phospholipid levels, renal function (proteinuria and GFR), glomerular histology, glomerular macrophage infiltration, urinary prostaglandin levels (thromboxane B2 (TxB2), 6-keto-PGF1 alpha), plasma lipid levels, and blood pressure were measured. Diets were well tolerated by all groups with a similar age-related gain in weight throughout the study. Efficacy of the PUFA diets was confirmed by alteration in renal tissue phospholipids; LA decreased in the RLD and BO groups, but not in the CO group. AA was higher in the BO and CO rats, but only the BO group showed a rise in GLA and DGLA incorporation. Proteinuria increased progressively in the RLD group but remained at 1-wk postsurgery levels in the BO and CO groups. Decline in GFR and mesangial expansion were significantly lessened by BO supplementation only. Both PUFA diets limited glomerulosclerosis and macrophage infiltration, but direct comparisons between BO and CO groups revealed significantly less glomerulosclerosis and macrophage infiltration in the BO group. Both BO and CO attenuated the rise in the TxB2 excretion rate and restored the 6-keto-PGF1 alpha:TxB2 ratio to the 1-wk postsurgery level. Plasma lipid levels rose in all groups, but the rise in cholesterol level was less in the BO and CO rats, CO being the most efficacious in this regard. BP increased progressively in RLD rats, but not in the BO and CO groups, BO providing a markedly greater hypotensive effect. In summary, both CO and BO supplemented PUFA diets limited glomerular injury in the renal-ablated rats. However, BO supplementation was more effective than CO supplementation at preserving GFR, limiting mesangial expansion and glomerulosclerosis, and reducing glomerular macrophage infiltration.

8,11,14-Eicosatrienoic Acid↗

PubMed1995

Effects of flaxseed and flax oil diets in a rat-5/6 renal ablation model.

The objective of this study was to assess the effects of flaxseed and flax oil diets in the rat renal ablation model. Flaxseed is a rich source of alpha-linolenic acid, an 18:3n3 omega-3 fatty acid, which has anti-atherogenic and anti-inflammatory properties. Flaxseed, but not flax oil, is also rich in lignans, which are platelet-activating factor-receptor antagonists. Rats were subjected to 5/6 nephrectomy, fed a regular laboratory diet (RLD) for 1 week, then divided into three groups to receive either the RLD (n = 8), a 15% flaxseed diet (n = 8), or a 15% flax oil diet (n = 7). Blood pressure, proteinuria, glomerular filtration rate, and urinary prostaglandins (thromboxane B2 and 6-keto prostaglandin F1 alpha) were measured presurgery and at 1 week (before dietary allotment) and 20 weeks postnephrectomy when blood for plasma lipids and kidneys for histology and tissue-phospholipid analyses were obtained. Blood pressure increased progressively in the RLD group but not in the flax diet groups. Plasma triglycerides and cholesterol increased in all groups, but this increase was significantly attenuated by both flax diets. Proteinuria increased 1 week postsurgery and continued to increase in the RLD group but not in the flax diet groups. Glomerular filtration rate decreased progressively, but this decline in renal function was attenuated significantly by the flax diets. Both of the flax diets prevented glomerulosclerosis and mesangial expansion. Renal alpha-linolenic acid was increased by both the flax diets (flax oil > flaxseed), but eicosapentaenoic acid increased in the flax oil group only. The flaxseed group had greater renal-arachidonic acid levels than the flax oil and RLD groups. The total omega-3 fatty acids increased twofold to threefold in the flax oil group compared with the two other groups. The total saturated fatty acids were lower and the polyunsaturated fatty acids were increased in both flax diet groups. A progressive increase in urinary thromboxane B2 occurred in the RLD group but not in the flaxseed group; the level decreased in the flax oil group. The ratio of prostaglandin F1 alpha/thromboxane B2 was preserved in the flax oil group only. In conclusion, the dietary flax seed and flax oil attenuated the decline in renal function and reduced glomerular injury with favorable effects on blood pressure, plasma lipids, and urinary prostaglandins. While we have not proven any specific synergistic effects of the constituents of the flaxseed diet, the benefits of flax-derived alpha-linolenic acid with or without lignans in the rat-5/6 renal ablation model seem clear from this experiment.

6-Ketoprostaglandin F1 alpha↗

PubMed1995

Flaxseed: a potential treatment for lupus nephritis.

Flaxseed is rich in alpha-linolenic acid (alpha-LA) which has anti-atherogenic properties, and lignans which are platelet activating factor (PAF)-receptor antagonists. These constituents of flaxseed, and its beneficial effects in the MRL/lpr lupus mouse prompted us to perform this dosing study in lupus nephritis patients. Nine patients were enrolled, eight of whom completed the study. After the baseline studies, patients were given 15, 30, and 45 g of flaxseed/day sequentially at four week intervals, followed by a five-week washout period. Compliance, disease activity, blood pressure, plasma lipids, rheology, PAF-induced platelet aggregation, renal function, and serum immunology were assessed. Flaxseed-sachet count and a significant increase of serum alpha-LA indicated good compliance for 15 and 30 g doses. Total and LDL cholesterol, and blood viscosity were significantly reduced with 30 g and to a lesser extent 45 g doses. PAF-induced platelet aggregation was inhibited by all doses. There was a significant decline in serum creatinine with 30 and 45 g, and a concomitant increase in creatinine clearance with increasing flaxseed dose. Proteinuria was reduced with 30 g and to a lesser extent with 45 g of flaxseed. Complement C3 was significantly elevated by all three doses. CD11b expression on neutrophils, a measure of C3bi receptors, was significantly reduced with the 30 g dose. In conclusion, 30 g flaxseed/day was well tolerated and conferred benefit in terms of renal function as well as inflammatory and atherogenic mechanisms important in the pathogenesis of lupus nephritis.

Adult↗

PubMed1995

Dietary supplementation with L-arginine limits cell proliferation in the remnant glomerulus.

One effect of L-arginine is to increase nitric oxide (NO) production by endothelial cells. NO directly reduces endothelin-1 production by endothelial cells and also inhibits platelet-derived growth factor (PDGF) induced cell proliferation. Since subtotal renal ablation is associated with an early phase of cell proliferation in the glomerulus that precedes injury, we examined the effect of dietary supplementation with L-arginine on glomerular cell proliferation and expression of the cytokine endothelin-1 (ET-1). A first group of renal-ablated rats was untreated. A second group of renal-ablated rats received L-arginine (1%) in the drinking water. Two weeks after subtotal ablation renal cortical tissue was snap frozen for immunohistochemical analysis for proliferating cell nuclear antigen (PCNA) expression and ET-1. Protein and total RNA was extracted from sieved glomeruli. mRNA levels were quantitated by co-amplification RT-PCR utilizing specific 5' and 3' primers for rat ET-1 and beta-actin. L-arginine reduced the number of PCNA positive nuclei in remnant glomeruli, and Western blot Analysis of glomerular proteins also showed that L-arginine reduced PCNA expression. Glomerular ET-1 mRNA levels and protein immunostaining declined in the rats receiving L-arginine. We conclude that dietary supplementation with L-arginine reduces early cell proliferation in the remnant glomerulus, an effect that may be mediated, in part, by a decrease in ET-1 production.

Animals↗

PubMed1994

Conformity with guidelines for antimicrobial prophylaxis against bacterial endocarditis.

The extent to which prescribed antimicrobial prophylaxis against bacterial endocarditis conformed with American Heart Association (AHA) guidelines was determined and the frequency of nonconformity with specific elements of the guidelines was evaluated. Patients with conditions defined by AHA as placing them at risk for developing endocarditis were identified through medical records for a four-year period at an 850-bed hospital. Data about the procedures they underwent and prophylaxis prescribed were compared with the AHA guidelines. Conformity with the guidelines was evaluated according to whether prophylaxis was recommended, optional, or unnecessary; nonconformity with specific elements of the guidelines (indication, choice of antimicrobial, dose, dosage interval, timing, and duration) was also evaluated. The following variables were evaluated for possible association with nonconformity to the guidelines: patient's age and sex, penicillin allergy, use of a consultant, and whether the procedure was the first performed in the patient after identification of the cardiac condition. Of the 131 cases analyzed, 29 (22%) involved prophylaxis that conformed with the AHA guidelines. Conformity with the guidelines was significantly lower when prophylaxis was recommended or optional than when it was unnecessary. Nonconformity was most common with the following elements: indication, choice of antimicrobial, and dose. Recommended prophylaxis was given more often in children than in adults and more often before first procedures than before subsequent procedures. More of the regimens prescribed for children exceeded the recommended duration than those prescribed for adults. Unnecessary prophylaxis was given more often when a consultant was involved than when no consultant was involved. In hospitalized patients, conformity with AHA guidelines for antimicrobial prophylaxis against endocarditis was low.

Adolescent↗

PubMed1994

Omega-3 fatty acid supplementation in clinical and experimental lupus nephritis.

Nutrients rich in omega-3 fatty acids (fish oil and flaxseed) have the potential to abrogate inflammatory and atherosclerotic mechanisms known to be involved in the pathogenesis of vascular damage of systemic lupus erythematosus nephritis. Fish oil dietary supplementation decreases proteinuria and preserves renal morphology in the NZB/NZW, BXSB, and MRL/lpr mouse models of lupus nephritis and decreases mortality in the NZB/NZW and BXSB models. The anti-inflammatory and anti-atherosclerotic potential, coupled with the animal experimental data, encouraged us to carry out a dosing study of low (6 g) and higher (18 g) doses of fish oil (MaxEPA) therapy in human lupus nephritis. At the lower dose, the fish oil inhibited inflammatory mechanisms; at the higher dose, it altered both the inflammatory and atherosclerotic mechanisms. This led to a double-blind cross-over study of fish oil therapy in 26 patients with lupus nephritis followed for 2 years 10 weeks. The fish oil dietary supplementation had no significant effect on proteinuria, isotope glomerular filration rate, disease activity index, or steroid consumption. However, it did have a significant effect on lipid levels. The cross-over design suffered carryover effects (even with a 10-week wash-out period) and placebo effects of the olive oil, which created a risk of type II error. Our interest in omega-3 fatty acids led us to assess the effects of dietary supplementation with flaxseed. Not only is the flaxseed a major source of alpha-linolenic acid but it is also the richest natural source of lignan, a natural platelet-activating factor receptor antagonist.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

Early dietary protein restriction slows disease progression and lengthens survival in mice with polycystic kidney disease.

The objective of these studies was to examine the effects of early dietary protein restriction on disease progression and survival in the DBA/2FG-pcy (pcy) mouse model of polycystic kidney disease. Male pcy mice of 70 days of age were fed either a normal protein (NP, 25% casein) or a low-protein (LP, 6% casein) diet for 105 days. At the end of the dietary treatment, kidney weight, kidney weight relative to body weight and kidney water contents were almost 50% lower, and relative renal phospholipid and triglyceride contents were almost 50% higher, in mice fed the LP diet, indicating a marked reduction in the progression of cystic disease. Morphometric analyses also revealed a lower total and percent cyst area in kidneys derived from mice on the LP compared with the NP diet. There were no significant differences in final body weight, urine volume and osmolality, GFR, proteinuria, or plasma levels of protein and urea between these two groups. In a second study, it was found that all mice fed an NP diet from 70 days of age onward had died by 310 days of age, compared with a 42% survival rate in LP-fed mice at this age. Overall, the mean lifespan for pcy mice on the LP diet was 24% longer than that for those mice on the NP diet (310 +/- 20 versus 251 +/- 16 days; P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

Abrogation of MRL/lpr lupus nephritis by dietary flaxseed.

A diet supplemented with flaxseed, rich in alpha-linolenic acid and plant lignans (the latter, potent platelet-activating factor receptor antagonists), was tested in a murine model of lupus nephritis. MRL/lpr female mice (n = 25) were fed 15% flaxseed diet for 14 weeks commencing at 10 weeks of age. As controls, 30 MRL/lpr mice received a standard rodent diet without flaxseed. Isotope-glomerular filtration rate (14C-inulin clearance) was measured at 9, 16, and 24 weeks of age. Proteinuria was assessed at 2-week intervals. Spleen lymphocyte proliferation, quantitated by DNA analysis, was evaluated using flow cytometry at 9, 13, 19, and 21 weeks of age. Mortality was recorded throughout the study. Glomerular filtration rate at 16 weeks was greater in flaxseed-fed mice (0.15 +/- 0.03 mL/min) compared with controls (0.06 +/- 0.04 mL/min; P = 0.01). The onset of proteinuria (Albustix, Ames Division, Miles Laboratories, Rexdale, Ontario, Canada; > or = 2+) was delayed by 4 weeks in the flax-treated mice. The percentage of flaxseed-fed mice with proteinuria was lower than the control mice up to 21 weeks of age (39% v 58%; P = 0.01). Spleen lymphocyte proliferation (percentage of cells in S-phase) at 13 weeks of age was significantly higher in the control group (22.9 +/- 5.0, P = 0.01) but not in the flaxseed group (17.2 +/- 4.9) compared with baseline (9 weeks of age) values (13.0 +/- 3.5). Mortality was lower in the flaxseed-fed mice versus the control mice (assessed by Mantel-Haenszel (log-rank) test; P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

Fish oil in lupus nephritis: clinical findings and methodological implications.

Our objective was to determine the effects of fish oil on renal function, symptoms, and serum lipids in patients with lupus nephritis. A double-blind, randomized crossover trial of fish oil versus placebo (olive oil) was done on 26 patients with confirmed systemic lupus; 21 completed the study. Intervention was fish oil or placebo, 15 g/day, for one year followed by a 10 week wash-out period, and then the reverse treatment for one year. At baseline and six month intervals, we measured platelet membrane fatty acids, indices of renal function, a disease activity index, serum lipid levels, blood pressure, serum viscosity and red cell flexibility. We found that platelet membrane phospholipids were uniformly affected by fish oil supplementation (P < 0.001) but with significant carry-over effects despite a 10 week wash-out period. Glomerular filtration rate and serum creatinine were not affected. A non-significant reduction in mean (SE) 24-hour proteinuria occurred, from 1424.1 mg (442.7) on placebo to 896.7 mg (352.2) on fish oil (P = 0.21). Fish oil lowered serum triglycerides from 1.89 (0.25) mmol/liter to 1.02 (0.11) mmol/liter (P = 0.004). VLDL cholesterol decreased markedly whether patients initially received fish oil or placebo (P = 0.004). The size of the reduction was affected by the order of treatment (P = 0.03), but parallel comparisons were significant before the crossover (P = 0.0006). With the possible exception of bleeding time, no other treatment effects were shown with fish oil. However, treatment order effects were seen in urinary IgG excretion (P = 0.03), whole blood viscosity (P < 0.0001), red cell flexibility (P = 0.004), and bleeding time (P = 0.06). In conclusion, one year of dietary supplementation with fish oil in patients with stable lupus nephritis did not improve renal function or reduce disease activity, but did alter some lipid parameters. Hitherto unreported carry-over effects and treatment order effects caused by the olive oil created a risk of type II error, and bear methodologic consideration in the design of future studies.

Adult↗

PubMed1993

Dietary protein restriction versus fish oil supplementation in the chronic remnant nephron model.

Dietary protein restriction and fish oil supplementation (MaxEPA) have been reported to have favourable effects on the remnant nephron model. In the present study female Munich-Wistar rats underwent 5/6 renal ablation (60 rats) or sham surgery (20 rats). The renal ablation rats were randomized one week post-surgery to receive a diet that contained either regular laboratory diet (RLD), 6% low protein diet (LPD) or 24% fish oil diet (FOD) supplementation. Mortality rates at 10 and 20 weeks post-surgery were not different amongst the RLD, LPD or FOD renal ablation cohorts. However the G.F.R. was significantly preserved in the FOD and LPD versus the RLD renal ablation rat groups. Both the LPD and FOD decreased albuminuria and gammaglobulinuria but LPD was more effective. Both dietary interventions prevented glomerulosclerosis but only LPD significantly reduced mesangial expansion. The FOD diet prevented intraglomerular fibrin formation and the LPD had no effect. The dyslipidemia noted at 20 weeks in the renal ablation group was significantly abrogated by both FOD and LPD, although only LPD prevented the heavy proteinuria. The LPD rats gained significantly less weight than the FOD and RLD cohorts. FOD exerted a significantly greater effect on blood pressure reduction than the LPD and also produced significant changes in the renal tissue phospholipids. These results indicate that protein restriction and fish oil supplementation preserve renal structure and function in the remnant nephron model but have different effects on mechanisms known to be co-factors in the progressive renal injury.

Animals↗

PubMed1992

Omega-3 fatty acid supplementation in primary nephrotic syndrome: effects on plasma lipids and coagulopathy.

The effect of fish oil dietary supplementation on the dyslipidemia and coagulopathy of seven patients with nephrotic syndrome and hypoalbuminemia due to primary kidney disease was studied. Plasma lipids, platelet aggregation studies, simplate bleeding time, and fibrinogen levels were determined before and after 6 wk of treatment with fish oil (15 g/day of MaxEPA; 2.7 g of eicosapentenoic acid (EPA) and 1.8 g of docosahexenoic acid. Urea kinetics were determined from urine-urea concentration, urinary proteina, and urine volume. A 3-day dietary intake record was obtained from each patient before and after 6 wk of fish oil supplementation. There was no significant dietary change in protein, fat, or carbohydrate intake over the time period of the study. At study end, total triglycerides decreased from 2.98 +/- 1.31 to 2.18 +/- 1.14 mmol/L (P = 0.002), and very low-density lipoprotein-triglycerides decreased from 2.35 +/- 1.34 to 1.28 +/- 1.07 mmol/L (P = 0.01). Low-density lipoprotein (LDL) cholesterol increased from 5.18 +/- 1.74 to 7.35 +/- 2.83 mmol/L (P = 0.005). No significant changes occurred in bleeding time, platelet count, hematocrit, red blood cell flexibility, or whole blood viscosity. Platelet aggregation responses to collagen and arachidonic acid were consistently reduced after treatment, but there was no change in platelet response to ADP. The platelet membrane phospolipids showed a significantly increased incorporation of EPA after the fish oil diet (P = 0.03).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1992

Heparin-induced thrombocytopenia in renal failure.

A 35-year-old patient with symptomatic chronic renal failure secondary to hereditary nephritis underwent heparinization during urgent hemodialysis. Subclavian catheter insertion was complicated by staphylococcal septicemia which precluded Gore-tex graft placement. Arteriovenous fistula failed immediately postoperatively and thrombectomy was required. Heparin-induced thrombocytopenia was suspected and the test was strongly positive. Acetyl salicylic acid (ASA) 40 mg, was used with heparin for dialysis, and there were no episodes of gastrointestinal hemorrhage or access site thrombosis. The use of very low-dose ASA in this setting is reported.

Adult↗

PubMed1991

Tolerance to nicotinic acid flushing.

The mechanism of tolerance to nicotinic acid flushing was determined in subjects during a 5-day course of treatment. Objective measures of skin blood flow were used to confirm the development of tolerance. Plasma levels of nicotinic acid showed marked intraindividual variability but were not decreased with the development of tolerance. However plasma levels of 9-alpha 11-beta prostaglandin F2, a stable metabolite of prostaglandin D2, became undetectable in most subjects with the development of tolerance. Thus tolerance is not associated with decreased levels of nicotinic acid or development of tolerance to the prostaglandin mediator, but with decreased levels of the mediator.

Administration, Oral↗