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Biomedical subjects

W F Clark

Publications and source records attributed to W F Clark.

At least 19 recordsLinked to original sources

Association between renal insufficiency and malnutrition in older adults: results from the NHANES III.

BACKGROUND: The extent to which relevant confounding variables influence the recognized association between renal insufficiency and malnutrition is not known. This study examined whether renal insufficiency was associated with malnutrition, independent of relevant demographic, social, and medical conditions in noninstitutionalized adults 60 years of age and older. METHODS: Participants (5248) in the United States Third National Health and Nutrition Examination Survey (NHANES III, 1988 to 1994), a cross-sectional study, were examined in a multivariate logistic regression model. Participants were stratified into three groups of glomerular filtration rate (GFR) by serum creatinine. Dietary and nutritional factors were estimated from 24-hour dietary recall, biochemistry measurements, anthropometry, and bioelectrical impedance. Participants were malnourished if they demonstrated at least three of the following five criteria: (1) serum albumin < or =37 g/L, (2) male weight < or =63.9 kg, female weight < or =51.8 kg, (3) serum cholesterol <4.1 mmol/L, (4) energy intake <15 kcal/kg/day, and (5) protein intake <0.5 g/kg/day. RESULTS: A GFR <30 mL/min/1.73 m(2) was present in 2.3% of men and 2.6% of women; these participants demonstrated low energy and protein intake and higher serum markers of inflammation. Thirty-one percent of individuals with malnutrition demonstrated a GFR <60 mL/min/1.73 m(2). In multivariate analysis, a GFR <30 mL/min/1.73 m(2) was independently associated with malnutrition [odds ratio 3.6 (2.0 to 6.6)] after adjustment for relevant demographic, social and medical conditions. CONCLUSIONS: It is probable that renal insufficiency is an important independent risk factor for malnutrition in older adults. Malnutrition should be considered, prevented, and treated as possible in persons with clinically important renal insufficiency. These results should be confirmed in a prospective longitudinal cohort study.

Aged↗

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↗

Frequently relapsing thrombotic thrombocytopenic purpura treated with cytotoxic immunosuppressive therapy.

BACKGROUND AND OBJECTIVES: Treatment of thrombotic thrombocytopenic purpura (TTP) with plasma exchange has reduced mortality rates from 90% in untreated cases to less than 20%. Despite plasma exchange, relapses may occur in as many as 40% of cases. Multiple relapses occur in a minority but pose a significant therapeutic challenge. Recent evidence supports the presence of an autoantibody which inhibits proteolysis of von Willebrand factor (vWF) in active TTP, allowing large multimers of vWF to form and promote platelet aggregation. Additional evidence suggests autoantibodies activate capillary endothelium and promote platelet aggregation in the microcirculation. Immunosuppression, thus, has a biologically plausible role in TTP. We describe three consecutive cases of relapsing TTP treated with cytotoxic therapy to highlight the potential role of immunosuppression. DESIGN AND METHODS: Cytotoxic immunosuppressive therapy with either cyclophosphamide or azathioprine was used in three consecutive patients with frequently relapsing TTP. RESULTS: All three patients have maintained remissions of 8 to 10 months without recurrence. INTERPRETATION AND CONCLUSIONS: Cytotoxic immunosuppressive therapy may have a role in inducing long-term remissions in recurrent TTP.

Adult↗

To pay or not to pay? A decision and cost-utility analysis of angiotensin-converting-enzyme inhibitor therapy for diabetic nephropathy.

BACKGROUND: Angiotensin-converting-enzyme (ACE) inhibitor therapy can significantly delay the progression of diabetic nephropathy to end-stage renal failure (ESRF). The main obstacle to successful compliance with this therapy is the cost to the patients. The authors performed a cost-utility analysis from the government's perspective to see whether the province or territory should pay for ACE inhibitors for type I diabetic nephropathy on the assumption that cost is a major barrier to compliance with this important therapy. METHODS: A decision analysis tree was created to demonstrate the progression of type I diabetes with macroproteinuria from the point of prescription of ACE inhibitor therapy through to ESRF management, with a 21-year follow-up. Drug compliance, cost of ESRF treatment, utilities and survival data were taken from Canadian sources and used in the cost-utility analysis. One-way and two-way sensitivity analyses were performed to test the robustness of the findings. RESULTS: Compared with a no-payment strategy, provincial payment of ACE inhibitor therapy was found to be highly cost-effective: it resulted in an increase of 0.147 in the number of quality-adjusted life-years (QALYs) and an annual cost savings of $849 per patient. The sensitivity analyses indicated that the cost-effectiveness depends on compliance, effect of benefit and the cost of drug therapy. Changes in the compliance rate from 67% to 51% could result in a swing in cost-effectiveness from a savings of $899 to an expenditure of more than $1 million per additional QALY. A 50% reduction in the cost of ACE inhibitors would result in a cost savings of $299 per additional QALY with compliance rates as low as 58% in the provincial payment strategy. INTERPRETATION: Provincial coverage of ACE inhibitor therapy for type I diabetes with macroproteinuria improves patient outcomes, with a decrease in cost for ESRF services.

Angiotensin-Converting Enzyme Inhibitors↗

Pauci-immune renal vasculitis: natural history, prognostic factors, and impact of therapy.

The purpose of this study is to describe the clinical presentation and natural history of pauci-immune renal vasculitis and determine whether particular presenting features or administered therapies predict outcome. We reviewed our experience since 1984 with such vasculitides, and 94 cases of pauci-immune vasculitis were identified. Presenting features were as follows: men, 63%; mean age at biopsy, 59 years; and mean serum creatinine level, 5.0 mg/dL. Patients with no extrarenal involvement had a tendency to present with a greater serum creatinine level. Since the antineutrophil cytoplasmic autoantibody (ANCA) assay became available, 77% of the patients tested were ANCA positive. In terms of natural history, 27 patients required dialysis immediately, there were 22 renal relapses, 28 patients progressed to dialysis, 10 patients died before requiring dialysis, 19 patients were lost to follow-up, and 37 patients remain active, not on dialysis. Overall, half the patients recovered some renal function, one third remained stable, and one sixth deteriorated. Female sex and angiotensin-converting enzyme inhibitor use predicted favorable outcome (P < 0.05). Advanced age, male sex, respiratory tract involvement, and a greater relapse rate predicted unfavorable outcome (P < 0.05). The incidence of pauci-immune renal vasculitis appears to be increasing, likely related to the emergence of the ANCA assay. Attempts to classify patients based on existing schemes may result in delayed diagnosis and therapy, with subsequent poorer outcomes. Also, given the increased mortality of patients with respiratory tract involvement, we speculate that respiratory tract disease therapeutic and monitoring regimens are ineffective. In general, we conclude that pauci-immune renal vasculitis is a heterogeneous disorder with an unfavorable prognosis.

Anti-Inflammatory Agents↗

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↗

Therapeutic plasma exchange: an update from the Canadian Apheresis Group.

In 1997, the Canadian Apheresis Group reviewed data on 103,416 plasma exchange procedures that had been collected since 1980. Although the number of plasma exchanges gradually increased (from 3189 to 8208 per year), the pattern changed. In 1981, the five most frequent indications for plasma exchange resulted in 55% of all such procedures; by 1997, the five most frequent indications for plasma exchange resulted in 81.1% of all such procedures. During this period, three conditions that were originally among the most frequent indications for plasma exchange became among the least frequent. This paper reviews the published evidence that supports or refutes the use of plasma exchange in the category of the five most frequent indications from 1981 to 1997: thrombotic thrombocytopenic purpura, myasthenia gravis, chronic inflammatory demyelinating polyneuropathy, Waldenstrom macroglobulinemia, the Guillain-Barre syndrome, rheumatoid arthritis, systemic lupus erythematosus, and multiple sclerosis. For most disorders, use of plasma exchange procedures is correlated with published evidence, and the changing patterns of plasma exchange use by members of the Canadian Apheresis Group reflect published evidence. Annual center-by-center reviews of use of plasma exchange may also have influenced practice patterns.

Acute Disease↗

Plasma exchange in rapidly progressive renal failure due to multiple myeloma. A retrospective case series.

BACKGROUND/AIMS: To evaluate the effect of plasma exchange on renal function in patients with rapidly progressive renal failure secondary to multiple myeloma. METHODS: The study was done through a retrospective chart review using a standardized form at a tertiary care centre in southwestern Ontario. Patients were included in the study if they had a diagnosis of multiple myeloma and rapidly progressive renal failure. Multiple myeloma was defined by a bone marrow aspirate >15% plasma cells plus one of the following: serum monoclonal paraproteins, monoclonal light-chain excretion, or lytic lesions. Patients were excluded if they had evidence of chronic renal failure or failed to complete three plasma exchanges. Twenty-six patients were reviewed; of these 24 were followed up to 1 year. All patients received hydration, standard chemotherapy, and plasma exchange. The plasma exchange volume was 50 ml/kg of 50% normal saline and 50% human serum albumin. Primary outcome measures included (1) prevention of acute dialysis and (2) prevention of progression from acute to chronic dialysis; secondary end points included (1) a decrease in creatinine of 25% or more within 3 months of the last plasma exchange and (2) survival at 1 year. RESULTS: Sixteen of 24 patients, followed up to 1 year, did not require dialysis. Two patients required dialysis initially, but were able to come off dialysis after 3 months. Fourteen patients were alive at 1 year, 13 of whom were dialysis independent. Twelve of 13 dialysis-independent patients had a >25% reduction in creatinine at 3 months. Two patients were lost to follow-up after discharge and were not included in the analysis. CONCLUSIONS: This retrospective study suggests that plasma exchange may offer some benefit in preventing the initiation or continuation of dialysis in patients with rapidly progressive renal failure secondary to multiple myeloma. A randomized controlled prospective study is needed to determine whether plasma exchange should be recommended as a standard treatment for patients with rapidly progressive renal failure due to multiple myeloma.

Acute Kidney Injury↗

Renal transplantation for end-stage renal disease caused by systemic lupus erythematosus nephritis.

The 1975 observations of the Advisory Committee of the Renal Transplant Registry about systemic lupus erythematosus (SLE) remain largely unaltered. The SLE patient's survival after renal transplantation has improved, but remains similar to the non-SLE transplantation population. Disease activity declines throughout the transplantation period with a low rate of graft loss due to recurrent disease. There is slight discordant evidence about spontaneous renal recovery and graft survival rates in the SLE transplant population. The latter difference may relate to variances in the donor source (live-related versus cadaveric). The original report did not address the now well-recognized immediate- and long-term risks posed by the anti-phospholipid antibody syndrome, the accelerated rate of vascular disease, hematologic malignancies, and corticosteroid osteoporosis in the SLE transplant recipient.

Comorbidity↗

Management of chronic renal insufficiency in lupus nephritis: role of proteinuria, hypertension and dyslipidemia in the progression of renal disease.

Non-immune mechanisms appear to be important in the majority of patients with lupus nephritis and progressive renal injury. Proteinuria, hypertension and dyslipidemia are associated non-immune risk factors often implicated in the deterioration of kidney function. There is ample animal experimental evidence that they are independent risk factors for progressive renal injury and their treatment results in amelioration of renal function. Proteinuria and hypertension, unlike dyslipidemia, have been shown to be independent risk factors for progressive renal injury in patients with lupus nephritis. Treatment of hypertension and proteinuria in the diabetic and non-diabetic progressive renal disease population results in stabilization of kidney function. Response to treatment should target both blood pressure of 120/80 and significant reductions in protein excretion. If protein excretion rate is unaltered by use of an angiotensin-converting enzyme inhibitor and salt restriction, one might resort to the use of an angiotensin II antagonist. Treatment of the dyslipidemia following good control of proteinuria, blood pressure and dietary change may not alter renal progression but should provide similar protection from accelerated vascular disease to the non-renal dyslipidemia population.

Disease Progression↗

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↗

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↗

A controlled trial of cyclosporine in patients with progressive membranous nephropathy. Canadian Glomerulonephritis Study Group.

A controlled trial of cyclosporine in patients diagnosed with progressive membranous nephropathy (MGN) was carried out to determine whether cyclosporine (D) would be more effective than placebo (P) in reducing the rate of deterioration in renal function. Patients (N = 64) with MGN were placed on a restricted protein diet (< or = 0.9 g/kg) and followed closely for 12 months (Part 1). Patients at high risk of progression based on an absolute loss in creatinine clearance (CCr) of > or = 8 ml/min and persistent nephrotic range proteinuria (Pr) were selected and randomly assigned to either (D) (N = 9) or (P) (N = 8) for 12 months (Part 2). No differences in the two groups were noted at entry. After 12 months, the improvement in CCr slope in ml/min/month was significantly greater in the D patients (D + 2.1 vs. P + 0.5, mean difference 1.6; 95% CI 0.3 to 3.0, P < 0.02). This improvement was maintained in six of eight D (75%) over a mean follow-up period of 21 months. Daily Pr also improved with D (by month 3, D - 4.5 g/day vs. P + 0.7 g/day, P = 0.02) and was sustained in six of eight (75%) D patients. When Pr was expressed as a function of their concurrent CCr, the D versus P patients' time to halving was faster (P = 0.02) and absolute number higher (4/9 D vs 0/8 P). In the D group a trend towards worse hypertension and an increase in the number of transient rises in serum creatinine were noted.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

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↗

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↗

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↗

Treatment of lupus nephritis: immunosuppression, general therapy, dialysis and transplantation.

The treatment of patients with clinical lupus nephritis is based on a combination of our understanding of the natural history of the disease, a large number of anecdotal reports, and a small number of studies which demonstrate statistical treatment benefits. This review is directed towards the treatments (immunosuppressive, general therapy, and end-stage renal failure management) which have been demonstrated to have been, or not to have been, beneficial. Although the prognosis of patients with lupus nephritis is undergoing continuous improvement, this may relate as much to changes in general treatment measures as to specific immunosuppressive schedules.

Diet↗