An oral sorbent reduces overload of indoxyl sulphate and gene expression of TGF-beta1 in uraemic rat kidneys.

BACKGROUND: An oral adsorbent (AST-120) delays the progression of chronic renal failure (CRF). The aims of the present study are to determine the effects of AST-120 on the localization of indoxyl sulphate in uraemic rat kidneys, and to examine whether AST-120 reduces the renal cortical gene expression of transforming growth factor (TGF)-beta1, tissue inhibitor of metalloproteinase (TIMP)-1 and pro-alpha1(I)collagen, and ameliorates glomerular and tubulointerstitial injuries in uraemic rats. METHODS: Two weeks after 5/6-nephrectomy, 10 rats were divided into pairs such that both rats in each pair exhibited almost the same levels of serum creatinine, blood urea nitrogen and creatinine clearance. One rat from each pair was assigned to a control uraemic group, the other to a uraemic group which received AST-120 everyday for 11 weeks. The localization of indoxyl sulphate was studied by immunohistochemistry using a monoclonal anti-indoxyl sulphate antibody we had developed. The renal cortical gene expression was studied by using northern blotting. RESULTS: Rats treated with AST-120 showed decreased levels of serum creatinine, blood urea nitrogen and urinary protein as well as increased levels of creatinine clearance as compared with control uraemic rats. AST-120 markedly decreased indoxyl sulphate levels in both serum and urine. Immunohistochemistry demonstrated that indoxyl sulphate was localized in the renal proximal tubular epithelial cells, especially of dilated tubules, and that AST-120 markedly reduced the tubular staining of indoxyl sulphate. AST-120 attenuated interstitial fibrosis, tubular injury as well as glomerular sclerosis, and reduced the renal gene expression of TGF-beta1, TIMP-1 and pro-alpha1(I)collagen. CONCLUSIONS: AST-120 reduces the gene expression of TGF-beta1, TIMP-1 and pro-alpha1(I)collagen in the kidneys, and delays the progression of CRF, at least in part, by alleviating the overload of indoxyl sulphate on remnant proximal tubular epithelial cells.     

Lipopolysaccharide suppresses albumin expression by activating NF-kappaB in rat hepatocytes

BACKGROUND: The severity of hypoalbuminemia has been shown to be related to morbidity and mortality in critical illness, illustrating the need for better understanding of the molecular mechanism of hypoalbuminemia. Lipopolysaccharide(LPS) is a key mediator which induces hypoalbuminemia in sepsis and septic shock. The present studies were performed to identify whether the reduction of albumin expression induced by LPS was mediated by activating nuclear factor kappa B(NF-kappaB) in cultured rat hepatocytes. MATERIALS AND METHODS: Primary rat hepatocytes were divided into five groups treated with normal saline or 1 ng/ml, 0.01 microg/ml, 0.1 microg/ml, or 1 microg/ml of LPS for 24 h. The albumin level in the supernatant and NF-kappaB activity in hepatocytes were measured. Hepatocytes were pretreated for 30 min with SN50 (a highly selected inhibitor of NF-kappaB) at different concentrations (10, 30, and 50 microg/ml). After 24 h of treatment with 1 microg/ml of LPS, the culture medium was measured for albumin level. Meanwhile, NF-kappaB activity in hepatocytes was assayed. RESULTS: LPS dramatically decreased albumin expression and enhanced NF-kappaB activity in rat hepatocytes, especially in the 1 microg/ml LPS group. This reduction in albumin expression induced by LPS can be completely inhibited by SN50 in different concentrations, and the maximal increase in albumin was observed at a SN50 dosage of 30 microg/ml. CONCLUSIONS: The results suggest that LPS inhibits albumin expression by activating NF-kappaB signaling. NF-kappaB is a critical signaling pathway in LPS-induced hypoalbuminemia which it is worthwhile to understand in studying the molecular mechanism of hypoalbuminemia in sepsis and septic shock.     

Effects of chondroitin sulphate,human serum albumin and Tamm-Horsfall mucoprotein on calcium oxalate crystallization in undiluted human urine

Summary The effects of physiological concentrations of chondroitin sulphate, human serum albumin and Tamm-Horsfall mucoprotein on the crystallization of calcium oxalate in undiluted, ultrafiltered human urine were investigated using particle size analysis and scanning electron microscopy. Neither the amount of oxalate required to induce detectable calcium oxalate crystal nucleation nor crystal morphology was affected by the presence of any of these macromolecules. Chondroitin sulphate had no effect on the amount of crystalline material deposited or on the size of the particles precipitated in response to a standard oxalate load. Human serum albumin slightly reduced the size of the crystal aggregates and caused a small increase in the amount of crystal matter precipitated. By contrast, Tamm-Horsfall mucoprotein significantly inhibited crystal aggregation and markedly increased the volume of matter deposited, although this could not be attributed to a promotion of solute precipitation. It was concluded that chondroitin sulphate, human serum albumin and Tamm-Horsfall mucoprotein cannot account for the inhibitory effects of macromolecules with a relative mass greater than 10 kDa in spun and filtered urine. Nonetheless, Tamm-Horsfall mucoprotein is likely to inhibit crystal aggregation in whole urine in vivo and may therefore be instrumental in preventing calcium oxalate stone formation.     

Enhanced long-term reduction of plasma leptin concentrations by super-flux polysulfone dialysers.

BACKGROUND: Hyperleptinaemia in chronic haemodialysis (CHD) patients has been associated with malnutrition, which is an independent predictor of morbidity and mortality in this patient group. METHODS: To assess the influence of HD on plasma leptin, 10 CHD patients were crossover randomized to low-flux polysulfone (PS: F 6HPS), high-flux PS (F 60S), super-flux PS (F 500S) or super-flux cellulose-tri-acetate (CTA: Tricea 150G) for 12 weeks each. Blood samples were collected at the start of the study and each 12-week period. In addition, the relationship between patient characteristics, inflammation and leptin was analysed. RESULTS: At baseline, all groups showed similar leptin concentrations (mean 33.6+/-21.7 ng/ml). After a single HD session, a significant (P<0.01) decrease was observed with all three high permeable devices (Tricea 150G -52.7+/-6.4%; F 60S -63.1+/-5.7%; F 500S -68.7+/-8.2%), whereas leptin remained stable with low-flux PS. After 12 weeks, a marked increase was observed with low-flux PS (week 1, 30.4+/-23.0; week 12, 40.5+/-5.4 ng/ml, P = 0.05), no change with super-flux CTA and high-flux PS (Tricea 150G week 1, 29.4+/-23.7; week 12, 32.0+/-27.9 ng/ml, P = ns; F 60S week 1, 36.0+/-31.8; week 12, 33.0+/-31.2 ng/ml, P = ns), and a significant decrease with super-flux PS (week 1, 38.3+/-33.0; week 12, 29.5+/-31.9 ng/ml, P = 0.02). The change in leptin after 12 weeks was significantly different between super-flux PS, and both low-flux PS (P = 0.009) and super-flux CTA (P = 0.01). Besides interleukin-6 (IL-6) at the start of the study (P = 0.006), no correlations were observed between patient characteristics, parameters of inflammation and plasma leptin levels. CONCLUSIONS: Apart from low-flux PS, plasma leptin decreased considerably with all three high permeable dialysers after a single HD session. In the long run, leptin levels were lower with high-flux PS than with low-flux PS. Moreover, after switching from high-flux PS to super-flux PS (but not super-flux CTA), an additional decrease in leptin was observed. Apart from IL-6 at the start of the study, neither patient characteristics nor inflammatory parameters correlated with plasma leptin levels in this patient group.     

脂多糖激活大鼠库普细胞产生的递质对肝细胞损害的影响

目的　探讨库普细胞 (KC)产生的活性递质对肝细胞的损害作用。方法　将脂多糖(LPS)刺激KC后产生的活性递质加入同时培养的肝细胞中 ,并观察肝细胞肝功能的变化。结果　KC上清中TNFα、IL - 6和NO的浓度增高的同时 ,培养肝细胞GOT和GPT增高 ,同时ALB降低。结论　LPS刺激KC后产生的活性递质能明显损伤肝细胞     

Relationship between serum albumin level before initiating haemodialysis and angiographic severity of coronary atherosclerosis in end-stage renal disease patients.

BACKGROUND: In patients with chronic kidney disease (CKD), although strong associations have been observed between malnutrition and atherosclerosis, the relationship between serum albumin concentration and angiographic changes of coronary artery disease (CAD) remains poorly explored. The goal of the present study was, in patients with CKD, to clarify the relationship between the angiographic severity of CAD and serum albumin concentration reflecting either inflammation or nutrition or both. METHODS: In this study, 100 end-stage renal disease (ESRD) patients were enrolled, who commenced long-term dialysis therapy at our hospital and underwent coronary angiography within 3 months of the first haemodialysis (HD) session. Mean age was 63+/-11 years, 20% of the subjects were female and 62% had diabetes. Severity of CAD was evaluated in terms of (i) number of vessels exhibiting CAD (>or=75% stenosis) and (ii) Gensini score (GS). Clinical characteristics and laboratory findings were recorded at initiation of long-term HD therapy. We then evaluated a possible association with the presence and degree of CAD. RESULTS: Sixty-four patients exhibited signs of CAD. Forty-one among them (64%) had multivessel disease. On univariate logistic regression analysis, age, diabetes and hypoalbuminaemia were significantly associated with multivessel CAD. Univariate linear regression analysis demonstrated a positive correlation of age and diabetes with GS, and an inverse correlation of BMI and serum albumin level with GS. Stepwise regression analysis showed age and serum albumin level to be independently associated with multivessel CAD and GS. The ROC curves demonstrated best cut-off levels of age and albumin for predicting multivessel CAD to be 70 years and 3.15 g/dl, respectively. CONCLUSION: Hypoalbuminaemia at the initiation of dialysis is an important predictor of advanced CAD, particularly in male and in diabetic patients. It may reflect mainly a state of inflammation. However, malnutrition as a confounding factor cannot be entirely excluded.     

Effect of interleukin 6 on basal and FSH-stimulated secretion of estradiol and progesterone by human granulosa cells in vitro

Aim: To determine the effects of interleukin-6 (IL-6) on the secretion ofestradiol and progesterone by human granulosa cells in vitro. Methods:Granulosa cells were obtained from infertile patients undergoing IVF ETtreatment and cultured with serum-free supplemented HAM's F10 medium.In the absence or presence of FSH, granulosa cells were treated with differ-ent concentrations of gene recombinant human iterlukin-6 (rhIL-6). Themedia were collected after 24, 48, 72 and 96 h and assayed for estradiol andprogesterone. IL-6 and R mRNA was determined by means of RNA slotblot. Results: IL-6 had a significant inhibitory effect on estradiol secre-tion, especially in the presence of FSH. IL-6 inhibited the FSH-stimulatedprogesterone secretion, but not the basal progesterone release. The inhibi-tion shows certain degrees of dose- and time-dependency. Conclusion:IL-6 participates in the regulation of ovarian function through its inhibitoryeffect on FSH-stimulated steroidogenesis by granulosa cells.     

Influence of nutritional status on plasma and erythrocyte sulphur amino acids, sulph-hydryls, and inorganic sulphate in end-stage renal disease.

BACKGROUND: The metabolism of sulphur amino acids and sulph-hydryls is altered in end-stage renal disease (ESRD). Previous studies have focused on the role of vitamin status in the development of hyperhomocysteinaemia in such patients, but little information exists about the influence of global nutritional status and hypoalbuminaemia on sulphur-containing compounds in ESRD. As considerable fractions of sulph-hydryls in blood are present in erythrocytes (RBC), which among others participate in intra-organ amino acid transport, the relationship between plasma and RBC levels of several of these compounds and various nutritional parameters were evaluated in the present study. METHODS: Thirty-seven ESRD patients (24 males, 13 females) on dialysis treatment (18 haemodialysis, 19 continuous ambulatory peritoneal dialysis) and 21 healthy subjects (seven males, 14 females) were examined. The subjective global nutritional assessment (SGNA) showed that 10 (27%) patients were malnourished and 27 (73%) had normal nutritional status. RESULTS: All the ESRD patients had high plasma total homocysteine (tHcy) levels. The plasma concentrations of methionine (Met) and taurine (Tau) were low, but the levels of the other sulphur-containing compounds were high. In the RBC, the patients had higher levels of tHcy and Tau than in healthy subjects, but no difference was seen in the concentrations of glutathione (GSH), cysteinylglycine (Cys-Gly), Met, and Cys. The plasma inorganic sulphate concentrations were five times higher in the patients than in healthy subjects, but the levels did not differ significantly between the malnourished patients and those with normal nutritional status. The malnourished patients had lower plasma, but not RBC, levels of tHcy, GSH, and Cys-Gly than those with normal SGNA. Plasma tHcy correlated positively with serum (s)-albumin and anthropometric parameters and negatively with SGNA. RBC and whole blood, but not plasma, GSH concentrations were correlated with haematocrit and were significantly lower in low haematocrit patients (< or = 37%, n = 19) than in those with a high haematocrit (> 37%, n = 18). CONCLUSIONS: These results show that nutritional status and s-albumin influence plasma, but not RBC, concentrations of sulph-hydryls in ESRD patients. This should be considered when the relationships between cardiovascular disease and plasma tHcy or other sulphur-containing compounds are assessed. The study also shows that GSH concentrations in RBC and whole blood are related to haematocrit and not to nutritional parameters, indicating that anaemia status rather than nutritional status determines RBC and whole blood GSH levels in ESRD patients.     

联合应用骨化三醇和钙剂对绝经后骨质疏松症患者血清IL-6、TNF-α的影响

目的 观察联合应用骨化三醇和钙剂对绝经后妇女骨质疏松症患者血清IL-6和TNF-α的影响,探讨其作用机理.方法 70例绝经后妇女骨质疏松症患者随机分两组:治疗组35例服用骨化三醇(0.5 μg·d-1)和钙剂(1000 mg·d-1);钙剂组35例服用钙剂(1000 mg·d-1),用药前与用药6个月后,用ABC-ELISA法分别检测血清IL-6和TNF-α的含量.结果 治疗后骨化三醇治疗组血清IL-6、TNF-α的浓度较治疗前降低,差异均有统计学意义(P<0.05),而钙剂对照组与治疗前比较,差异无统计学意义 (P>0.05).联合应用骨化三醇和钙剂组与单独应用钙剂组相比,患者血清IL-6、TNF-α的浓度差异有统计学意义(P<0.05).结论 骨化三醇可通过降低患者血清IL-6和TNF-α水平发挥抗骨丢失作用,而且联合应用钙剂较单独应用钙剂治疗绝经后妇女骨质疏松症效果更好.     

Effect of the duration of dialysis on survival in a cohort of chronic haemodialysis patients.

BACKGROUND: Atherosclerosis and vascular calcification are common in chronic haemodialysis (HD) patients, and usually progress with time. Whether the length of dialysis treatment in chronic HD patients is a significant independent risk factor of death is not clear. METHODS: A cohort of chronic HD patients from the Okinawa Dialysis Study, n=1243 (720 men, 523 women), was followed from January 1991 to December 2000, and their survival rates were compared against the duration of HD, which was calculated in months from the start of dialysis therapy to January 1991. A Cox proportional hazards regression analysis was done to examine the influence of the duration of dialysis on survival, after adjusting for other factors such as age, sex, serum albumin concentration and diastolic blood pressure. The hazards ratio and 95% confidence interval (CI) were calculated in both diabetic and non-diabetic patients. RESULTS: The mean duration of dialysis was 61.9 months and ranged from 1 to 233 months. The numbers of patients who died, underwent renal transplantation or were transferred outside Okinawa were 568 (45.7%), 61 (4.9%) and 14 (1.1%), respectively, during the study. The hazards ratio (95% CI) was 1.002 (1.000-1.004, P=0.0245) for non-diabetic patients and 1.006 (1.001-1.011, P=0.0214) for diabetic patients, suggesting that the longer the duration of dialysis, the greater the risk of death. CONCLUSIONS: This study shows that prolonged dialysis is a significant predictor of death in chronic HD patients, in particular diabetic patients. Whether this is related to the progression of the atherosclerotic process or to uraemic conditions remains to be shown.     

溶脲脲原体感染对大鼠支持细胞分泌IL—1的影响

溶脲脲原体（ＵＵ）是泌尿生殖道感染的常见病原体，可导致睾丸明显的病理损伤，且与不育有关。本文以对数生长期的ＵＵ、ＵＵ上清（不含ＵＵ）和热灭活ＵＵ经体外感染或直接作用大鼠Ｓｅｒｔｏｌｉ细胞；检测细胞培养上清液中ＩＬ－１的活性。实验发现活ＵＵ感染和ＵＵ上清可明显抑制Ｓｅｒｔｏｌｉ细胞分泌ＩＬ－１的功能（Ｐ＜０．０１），其作用与ＵＵ剂量有关。提示：大鼠Ｓｅｒｔｏｌｉ细胞经ＵＵ感染后，其生物学功能可被抑制。     

内毒素诱导大鼠肝细胞白蛋白表达下降的分子机制

目的　探讨内毒素诱导肝细胞白蛋白表达下降的分子机制。方法　 1μg/ml内毒素刺激肝细胞后 ,分别在 0 ,2 ,8,12和 2 4h时留取肝细胞及上清检测白蛋白mRNA及其蛋白水平的变化。细胞内信号蛋白p38激酶和ERK激酶的特异性阻断剂SB2 0 35 80和PD980 5 9预处理肝细胞后检测上清中白蛋白的浓度。结果　内毒素刺激后 2 4h白蛋白mRNA下降约为 30 % ,与此同时白蛋白浓度下降约 5 0 %。SB2 0 35 80和PD980 5 9可以在体外抑制内毒素诱导肝细胞白蛋白表达的下降。结论　内毒素在转录水平抑制肝细胞白蛋白mRNA的表达来抑制白蛋白的合成。这一过程与细胞内信号传导通路p38和ERK激酶密切相关 ,进一步阐明了感染时低白蛋白血症的分子机制。     

Effect of the super-flux cellulose triacetate dialyser membrane on the removal of non-protein-bound and protein-bound uraemic solutes.

BACKGROUND: Uraemic solutes accumulate in haemodialysis (HD) patients and interfere with physiological functions. Low-flux (LF) HD does not efficiently remove all uraemic compounds. We investigated whether large pore super-flux (SF) cellulose triacetate membranes (CTA) result in a better removal of uraemic solutes. METHODS: Eleven patients were dialysed consecutively with LF-CTA and SF-CTA during 3 weeks. Urea (UR), creatinine (CR), uric acid (UA), 3-carboxy-4-methyl-5-propyl-2-furanpropionic acid (CMPF), indole-3-acetic acid (IAA), indoxyl sulfate (IS), hippuric acid (HA), pentosidine (PENT), low-molecular weight (MW) AGEs (AGEs) and albumin were determined in pre-HD, post-HD blood and in dialysate. Reduction rate (RR), dialytic clearance and mass transfer-area coefficient (KoA) were calculated. RESULTS: SF-HD resulted in a higher RR than LF-HD for IS and AGEs. Urea RR correlated with HA (r=0.59), IS (r=0.68) and IAA (r=0.67), (P<0.05) for SF. Dialytic clearance ranged from 20+/-5 to 179+/-20 ml/min for LF and from 24+/-6 to 191+/-24 ml/min for SF; being higher with SF for UA, HA, IS and IAA (SF vs LF, P<0.05). KoA was higher for most compounds with SF-HD. Albumin loss per SF session was 3.4+/-1.3 g. The retrieved amount of uraemic solutes in dialysate with LF and SF was comparable. CONCLUSIONS: In conventional HD, SF-CTA was superior to LF-CTA for removal of most protein-bound compounds, especially IS. Reduction rate, dialytic clearance and KoA were higher with SF. The SF-CTA membrane is albumin-leaking; however, this property could not completely explain the amount of retrieved protein-bound compounds in dialysate.     

Revisiting mortality predictability of serum albumin in the dialysis population: time dependency, longitudinal changes and population-attributable fraction.

BACKGROUND: Hypoalbuminaemia is a marker of malnutrition-inflammation complex syndrome (MICS) and a strong predictor of cardiovascular (CV) death in maintenance haemodialysis (MHD) patients. However, serum albumin may change over time. Hence, its time-varying associations with outcome may be different. METHODS: Associations between 3-month averaged serum albumin levels, measured in a single laboratory using bromocresol green, and CV mortality were studied longitudinally in a 2-year cohort of 58,058 MHD patients. Mortality predictability of fixed baseline and trimonthly-varying serum albumin concentrations were compared. RESULTS: Hazard ratios (HRs) of CV death strictly increased across decrements of baseline serum albumin, whereas the HR for time-varying serum albumin decrements below 3.8 g/dl did not differ. A drop in serum albumin in the first 6 months was associated with increasing all-cause and CV death risks in the subsequent 18 months, while a rise in serum albumin was a predictor of better survival independent of baseline serum albumin. The multivariate adjusted population-attributable fraction of death due to baseline serum albumin <3.8 g/dl was 19%. CONCLUSIONS: Time-varying hypoalbuminaemia predicts all-cause and CV death differently from fixed measures of serum albumin in MHD patients. An increase in serum albumin over time is associated with better survival independent of baseline serum albumin or other MICS surrogates. If this association is causal, an intervention that could increase serum albumin >3.8 g/dl might reduce the number of MHD deaths in the USA by approximately 10,000 annually. Nutritional interventions examining benefits of increasing serum albumin in MHD patients are urgently needed.     

HU308对脂多糖诱导小胶质细胞分泌NO及IL-6的影响

目的研究大麻素CB2受体激动剂HU308对脂多糖（LPS）诱导小胶质细胞激活后NO及IL-6分泌的影响。方法体外培养小鼠小胶质细胞株（BV-2细胞）,分为对照组、LPS刺激组及干预组（LPS＋HU308）。通过显微镜观察各组小胶质细胞的形态学变化,CCK-8法检测各组小胶质细胞的增殖情况,Griess法检测各组NO含量,ELISA法检测各组IL-6水平。结果LPS刺激组的小胶质细胞中出现大量胞体增大,伪足粗短或消失的细胞和一些坏死细胞,细胞增殖较差,NO及IL-6表达水平显著增高。经大麻素CB2受体激动剂HU308干预后,大部分细胞胞体稍大,伪足尚明显,细胞破坏程度轻,增殖较好,炎性因子表达均明显下降。结论激动小胶质细胞表面的大麻素CB2受体,可以减轻LPS造成的小胶质细胞过度活化或损伤,抑制其炎性因子N0及IL-6的分泌,从而达到中枢神经系统炎性损伤后的神经保护作用。     

Effect of immunosuppressive agents FK506 and cyclosporin and steroids on the expression of IL-6 and its receptor by stimulated lymphocytes and monocytes

Abstract The interaction of interleukin-6 (IL-6) with its receptor (IL- 6R) is not well understood. In the present study, we investigated the effect of different immunosuppressive agents on the expression of the couple IL-6/ IL-6R on cultured lymphocytes and monocytes. IL-6 in culture supernatants from cultured monocytes were analyzed by ELISA. The expression of IL-6R was studied by flow cytometry. Dexamethazone, cyclosporin (CyA), and FK506 at immunosuppressive concentrations induced a dose-dependent inhibition of IL-6 secretion from adherent monocytes (MO) stimulated with phytohemagglutinin (PHA). Dexamethazone was the most effective agent in inhibiting IL-6 secretion, while the inhibitory effect observed with 1 ngyml FK506 was comparable with that obtained with 100 ng/ml CyA. Unstimulated MO strongly expressed IL-6R (80% positive cells). Stimulation of MO with PHA resulted in a significant downregulation of IL-6R expression. Treatment of PHA-timulated adherent MO with different concentrations of CyA and FK S06 induced a restoration of IL-6 R expression. FKS06 was 100 time more effective in restoring IL-6R than CyA. This restoration of IL-6R was incomplete. FK506, CyA, and steroids may exert their immunosuppressive effect by inhibiting IL-6 secretion and partially restoring MO IL-6R, which may be important in protecting the cell target against IL-6 autocrine stimulation.     

Short-term effects of nocturnal haemodialysis on carnitine metabolism.

BACKGROUND: Functional carnitine deficiency [as indicated by an abnormal acyl-carnitine/free-carnitine (AC:FC) ratio] is commonly seen in patients with end-stage renal disease (ESRD), resulting in significant clinical detriments including anaemia, cardiomyopathy and muscle weakness. Nocturnal haemodialysis (NHD) (5-6 sessions per week, 8 h per treatment) has been reported to reverse several surrogate markers of uraemia. Conversely, as a consequence of increased dialysis dose, NHD may have the potential to aggravate plasma nutrient deficiencies. Our objective was to determine the effects of NHD on plasma free-carnitine levels and carnitine metabolism. METHODS: We conducted an observational cohort study with a before and after design. Nine ESRD patients (age: 47 +/- 3; mean +/- SEM) were studied. Routine biochemical, haemodynamic and carnitine metabolic products were analysed at baseline while on conventional haemodialysis and 2 months post-conversion to NHD. Free-carnitine and total-carnitine levels were generated by colorimetric assays. The difference between total- and free-carnitine concentrations was estimated to be the acyl-carnitine level. Paired t-test was used to ascertain statistical significance. RESULTS: After conversion to NHD, there was a significant increase in urea clearance in all patients. Plasma free-carnitine levels fell from 26.54 +/- 2.99 to 15.6 +/- 2.34 micromol/l (P < 000.1). A similar reduction in plasma acyl-carnitine levels was observed (from 13.22 +/- 1.34 to 6.24 +/- 1.20 micromol/l (P < 0.001)). The AC:FC ratio improved from 0.51 +/- 0.03 to 0.39 +/- 0.03 (P < 0.005) (Normal < 0.25). CONCLUSION: NHD is associated with an improvement in AC:FC ratio. Further research is needed to examine the longitudinal clinical impact of this metabolic correction and to examine whether this effect is sustained.