Comparative Effects of Haemodialysis and Haemofiltration on Plasma Atrial Natriuretic Peptide

The effects of 4 h haemodialysis (15 patients) or 4 h haemofiltration(five patients) on plasma concentrations of atrial natriureticpeptide (ANP) were compared by means of a sensitive radioreceptorbinding assay, and related to accompanying changes in body weight,blood pressure and plasma renin activity. Before dialysis, plasmaANP concentrations were considerably elevated: haemodialysisgroup 10–484 pmol/l (mean 156 pmol/l); haemofiltrationgroup 72–320 pmol/l (mean 170 pmol/l). Although plasmaconcentrations of ANP fell markedly with treatment in both groups:post-haemodialysis 2–187 pmol/l (mean 67 pmol/l); post-haemofiltration47–135 pmol/l (mean 79 pmol/l), after treatment it remainedabove the normal range in 14 of the 20 patients. Pretreatmentplasma ANP was related to systolic blood pressure (r=0.459;P<0.05) but bore no relationship to mean or diastolic bloodpressure, or plasma renin activity. The fall in plasma ANP concentrationduring treatment correlated with the postural blood pressuredrop after dialysis (r=0.505; P<0.05), but was unrelatedto changes in weight or plasma renin activity with haemodialysisor haemofiltration. Plasma ANP concentrations rose rapidly againin the 60 min after dialysis treatment, without change in bodyweight. These results show that high levels of biologically active ANPcirculate in end-stage renal disease. The fact that these arenot reduced to normal by haemodialysis or haemofiltration, despiterestoration to normovolaemic or hypovolaemic state, suggeststhat the increased levels of ANP in end-stage renal failureare due to both hypervolaemia and other factors, which may includeoccult cardiac dysfunction and loss of renal clearance.     

Effect of Fibronectin on C3b and Fc Receptor-mediated Phagocytosis by Peripheral Blood Monocytes in Uraemic Patients

The influence of human fibronectin was evaluated on the phagocytosisin vitro of C. albicans (C3b receptor-mediated) and IgG antibody-coatedsheep erythrocytes .(Fc receptor-mediated) by the peripheralblood monocytes of 40 uraemic patients undergoing periodic haemodialysis.Some nutritional parameters (albumin, transferrin, C4, C3, haematocrit,lymphocyte count, height and bodyweight) were also evaluated.Results showed significantly decreased plasma fibronectin (P<0.001)and reduced C3b receptor (R)- and FcR-mediated phagocytosisin uraemic patients (P<0.001). A strict correlation was foundbetween fibronectin and C3bR-mediated phagocytosis (P<0.001)and between fibronectin and FcR-mediated phagocytosis (P<0.05).In 20 patients with decreased fibronectin concentrations andreduced phagocytic function, the in vitro incubation of peripheralblood monocytes with 50 µg/ml of purified fibronectinsignificantly enhanced C3bR- (P<0.001) but not FcR-mediatedphagocytosis. Study of nutritional parameters in the uraemicpatients revealed that values of fibronectin, C3, IgG and albuminwere significantly reduced. Fibronectin correlated significantly(P<0.00l) with C3. A good relationship (P<0.05) was alsofound between the plasma fibronectin and bodyweight loss. Agreater incidence of infectious disease was observed in patientswith decreased plasma fibronectin than in uraemic patients withnormal values (P<0.05). The results suggest that a decreasein plasma fibronectin in uraemic patients could impair the peripheralblood monocyte phagocytic capacity and be potentially dangerous,predisposing the patient to infections. The determination offibronectin concentration in these patients may, therefore,have a potential value as an indicator of peripheral blood monocyte phagocytic function.     

Serum type I procollagen peptide: a non-invasive index of bone formation in patients on haemodialysis?

The value of serum procollagen peptide (PICP) as a non-invasiveindex of bone formation was studied in 18 patients establishedon haemodialysis. There was a significant correlation betweenPICP and serum alkaline phosphatase activity (ALP; r=0.55, P<0.05),and between PICP and osteocalcin (r=0.53, P<0.05). PICP alsocorrelated significantly with histomorphometric indices of boneformation, particularly bone formation rates (BFR) as estimatedby the tetracycline double-labelled technique (r=0.74, P<0.01),but not with those of bone resorption. There was a similar relationshipbetween BFR and ALP. From the regression analyses, a normalBFR was associated with normal PICP values despite the absenceof renal function, suggesting that the impact of renal functionon serum concentrations of PICP may not be large. Seven patientshad histochemical evidence for significant aluminium overload.th these patients the expected sup pression in biochemical andhistological indices of bone formation was associated with inappropriatelyraised PICP concentrations. The mechanism of this discrepancyis not clear, but caution is advocated in the interpretationof PICP in the presence of significant aluminium overload. Ourfindings otherwise suggest that PICP may be a useful non-invasiveindex of bone formation in patients on haemodialysis.     

Concentration of dimethyl-L-arginine in the plasma of patients with end-stage renal failure

Abstract. N^GN^Gdimethyl-L-arginine (asymmetric dimethyl-L-arginineADMA) and N^GN^G dimethyl-L-arginine (symmetric dimethyl-L-arginine;SDMA) are naturally occurring analogues of L-arginine, the substratefor nitric oxide (NO) synthesis. ADMA is a potent inhibitorof NO synthesis, and accumulates in the plasma of patients withrenal failure. However the precise concentration of ADMA andSDMA in renal patients is still controversial. This study wasperformed to measure plasma ADMA and SDMA concentrations bytwo different HPLC techniques in nine healthy controls and 10uraemic subjects, and to investigate the effects of haemodialysis.In controls, the mean (±SEM) plasma concentrations ofADMA and SDMA were 0.36±0.09 and 0.39±0.05 µmol/lrespectively, yielding an ADMA/SDMA ratio of 1.2± 0.17.In uraemic patients, the plasma concentrations of ADMA and SDMAwere 0.9±0.08 µmol/l (P<0.001 compared to controls)and 3.4±0.3 µmol/l (P<0.001 compared to controls)with an ADMA/SDMA ratio of 0.27±0.015 (P<0.001). Inthe course of one 4 h haemodialysis session, ADMA concentrationsdecreased from 0.99±0.13 to 0.77±0.3 µmol/land SDMA concentrations from 3.38±0.44 to 2.27±0.21µmol/l. The plasma ADMA/creatinine ratio tended to increasefrom 1.26±0.20 x 10^–3 to 2.01±0.41 x 10^–3It is concluded that there is a modest (3-fold) but definiteincrease in plasma ADMA concentration in uraemic patients comparedto controls. SDMA accumulates to a greater degree (8-fold increase)and more closely parallels creatinine concentration than ADMA.The change in the ADMA/SDMA ratio is not accounted for by greaterrenal or dialysis clearance of ADMA, and, even though alternativeexplanations are not excluded, greater metabolism of ADMA thanSDMA is the most likely explanation. Although small in magnitude,the increase in ADMA concentration might be biologically significant.     

Increased plasma levels of soluble tumor necrosis factor-receptors in uraemic patients: effects of dialysis, type of membrane, and anticoagulation method

Enhanced levels of soluble TNF-receptors (sTNF-R) have beenreported in patients with chronic renal failure. The aim ofthe present study was to evaluate the effects on sTNF-R levelsin plasma of haemodialysis patients of the anticoagulation methodand of the type of membrane used, as well as the variabilityof predialysis sTNF-R levels during time. All haemodialysispatients tested (n = 35) showed increased levels of both sTNF-R55(72.4 ± 5.7 ng/ml, P<0.001) and sTNF-R75 (18.2±2ng/ml,P<0.00l) before dialysis, as compared with normal healthycontrols (<2.5 ng7sol;ml for both sTNF-R), confirming previousobservations. sTNF-R levels were determined before and duringhaemodialysis at different time intervals in patients receivingeither heparin (2500 U, 5000 U, or 10000 U), low molecular weightheparin, or periodic saline flushing to prevent coagulationof the extracorporal circuit. A transient, small decrease inboth sTNF-R levels occurred at the beginning of haemodialysis(t=15 mm) with all anticoagulation methods used. At the endof haemodialysis, sTNF R55 and sTNF-R75 concentrations wereonly minimally affected (P<0.05). Predialysis sTNF-R levelswere similar in patients dialysed on either cellulose diacetateor polyacrylonitrile. Finally, there were only minimal variationsin predialysis sTNF-R levels in individual patients during the1 week observation period. Although the biological consequencesof the increased TNF-binding ability of serum from haemodialysispatients is still unclear, it could play a role in the compleximmunological perturbations of uraemic patients.     

The Effect of Lactate-Buffered Solutions on the Acid-Base Status of Patients with Renal Failure

We investigated the effect of an exogenous lactate load givenduring intermittent machine haemofiltration to three groupsof patients with renal failure: those with dialysis-dependentend-stage renal failure (6 patients) and those with either acuterenal (8 patients) and/or acute hepatorenal failure (6 patients).As expected, the hepatorenal group exhibited the greatest degreeof hyperlactataemia, and this was associated with the developmentof a metabolic acidosis. There were correlations between themaximum blood lactate measured during treatment and the increasein arterial hydrogen ion concentration (r=;0.76, P<0.001),and between the decrease in serum bicarbonate (r=0.89, P<0.001) and the mean arterial blood pressure prior to treatment(r= –0.57, P = 0.003). This suggests that hyperlactataemiais not as benign as previously thought and that lactate-bufferedfluids should be used with care in patients with hepatorenalfailure and cardiovascular instability.     

Subjective global assessment of nutrition in dialysis patients

Malnutrition is a major negative prognostic factor in dialysispatients. Simple and reliable estimations of nutritional statusmay therefore prove of particular value in the follow-up ofthese patients. To validate subjective global assessment (SGA)in dialysis patients we compared subjective global assessmentwith objective measurements (anthropometry, bioelectrical impedance,biochemical measurements) in 59 chronic uraemic patients treatedby haemodialysis (n = 36) or CAPD (n = 23). Subjective globalassessment was performed by an observer unaware of the resultsof objective measurements and was related to serum albumin (r= –0.51, P<0.001) and bioelectric impedance phase angle(r = –0.58, P<0.001) as well as with MAMC (r = –0.28P = 0.028), %fat (r = –0.27, P = 0.042) and nPCR (r =–0.29 P = 0.027). Multiple regression analysis showedthat the relationship of subjective global assessment (as adependent variable) with objective measurements (covariates)was stronger (multiple r = 0.77) than the relationship foundwith univariate analysis. This finding indicates that subjectiveglobal assessment gives a well-based and balanced estimationof nutritional status. Our data show that subjective global assessment is a clinicallyadequate method for assessing nutritional status in dialysispatients. Being an inexpensive method of well-proven reliability,subjective global assessment can be recommended for a more frequentassessment of nutritional status in dialysis patients.     

Increased serum concentrations of pro-gastrin-releasing peptide in patients with renal dysfunction

BACKGROUND: Gastrin-releasing peptide has a prominent role as a tumour markerin the diagnosis of small-cell lung carcinoma. This study wasdesigned to assess the validity of a newly developed enzyme-linkedimmunosorbent assay (ELISA) for pro-gastrin-releasing peptidein patients with renal and systemic diseases. METHODS: Pro-gastrin-releasing peptide concentrations in sera from normalsubjects and patients with small-cell lung carcinoma, diabetesmellitus, rheumatoid arthritis, systemic lupus erythematosus,chronic glomerulonephritis, or undialysed or dialysed chronicrenal failure were measured with the TND-4 Kit, a newly developedELISA for pro-gastrin-releasing peptide. RESULTS: All of the patients with normal renal function, whether theyhad diabetes mellitus (n=16), rheumatoid arthritis (n=10), systemiclupus erythematosus (n=12) or chronic glomerulonephritis (n=14),had serum pro-gastrin-releasing peptide concentrations lessthan 46 ng/l, the upper limit in normal subjects. In contrast,14 of 16 patients (88%) with small-cell lung carcinoma, whohad normal renal function, and 25 of 26 (96%) patients withchronic renal failure on haemodialysis had serum pro-gastrin-releasingpeptide concentrations greater than 46 ng/l. The highest serumpro-gastrin-releasing peptide levels in patients with chronicrenal failure, before and after initiating haemodialysis were183 and 290 ng/l respectively. Ten of 16 (63%) small-cell lungcarcinoma patients had serum pro-gastrin-releasing peptide concentrationsgreater than 290 ng/l, the highest level in haemodialysed patients.Serum pro-gastrin-releasing peptide concentrations were alsoelevated in patients with chronic glomerulonephritis or diabetesmellitus when their serum creatinine concentrations were greaterthan 120 µmol/l. And, there was a significant correlation,y=23.5+0.15x(n=22, r=0.82, P<0.001), between serum pro-gastrin-releasingpeptide (y, in ng/l) and serum creatinine (x, in µmol/l)concentrations in those patients with renal dysfunction. Thecorrelation between serum pro-gastrin-releasing peptide andserum urea nitrogen concentrations was likewise significant. CONCLUSIONS: The evaluation of patients as to their renal functional statemay be mandatory when serum pro-gastrin-releasing peptide levelsare to be applied as one of the diagnostic tools for small-celllung carcinoma or as a marker monitoring their clinical courses.     

Tumour necrosis factor soluble receptors I and II and interleukin-1 receptor antagonist in acute pyelonephritis in relation to bacterial virulence-associated traits and renal function

Urinary tract infections activate both mucosal and systemicinflammatory responses reflected by elevation of cytokine concentrationsin serum and urine. We determined urine and serum concentrationsof tumour necrosis factor soluble receptors I and II (sTNFRI and sTNFR II) and interleukin-1 receptor antagonist (IL-1ra)in 41 women with acute pyelonephritis caused by Escherichiacoli, 2 weeks after the infection, during a subsequent episodeof cystitis or asymptomatic bacteriuria and also later whenthe same patients were free from bacteriuria. Concentrationsof sTNFR I, sTNFR II and IL-1ra were related to the expressionof five virulence markers of E. coli, glomerular filtrationrate (GFR) and to the concentration of C-reactive protein (CRP)in serum. Patients with acute pyelonephritis had elevated serumconcentrations of sTNFR I and sTNFR II compared to healthy women(P<0.001 for both comparisons). The concentrations of sTNFRI and sTNFR II in urine were significantly higher in patientswith acute pyelonephritis compared to controls (P<0.001 inboth cases). The concentration of sTNFR II in urine was higherin patients infected by E. coli producing haemolysin (P=0.05)and in patients infected by E. coli expressing hydrophobic properties(P=0.05) compared to patients infected by strains without thesevirulence traits. Patients who had high concentrations of sTNFRII in serum during acute pyelonephritis had lower GFR at follow-up(r=–0.48, P=0.05). Patients who responded with a markedincrease in CRP had higher sTNFR I and sTNFR II in urine (r=0.58,P<0.01 and r=0.48, P<0.01, respectively). The concentrationsof sTNFR I and sTNFR II in serum and urine decreased duringfollow-up and were lower 2 weeks after the infection when allpatients were free from bacteriuria. IL-1ra in serum was elevatedduring pyelonephritis (P<0.001) while that in urine was significantlylower compared to controls (P<0.001). It is concluded thatthe     

Vitamin D3 Metabolites in Chronic Renal Failure and After Renal Transplantation

Circulating vitamin D3 metabolites were measured in 31 adultpatients with chronic renal failure and 31 adults between 3and 30 months after renal transplantation. No subject excretedover 1 g urinary protein daily nor received vitamin D or itsmetabolites. There was a positive correlation between 1,25(OH)₂D3and GFR between 15 and 90 ml/min in both chronic renal failure(r=0.60, P<0.001) and transplant subjects (r=0.49, P<0.01)and between 1.25(OH)₂ and 25(OH)D3 after transplant (r=0.69,P<0.001), but not in chronic renal failure (r=0.22, P=ns).There was a weak inverse correlation between 1,25(OH)₂D3 andserum phosphate in chronic renal failure (r=0.36, P<0.05)but not post transplant (r=0.03, P=ns). Compared with 1,25(OH)₂D3concentrations in 16 normal subjects (mean±SEM: 39.5±1.9 pg/ml), chronic renal failure subjects with mild renal impairment(GFR 45–90 ml/min, mean: 61.5±3.3 ml/min, n=17)had reduced 1,25(OH)₂D3 (28.9±2.7 pg/ml, P<0.01).In transplant subjects with mild impairment (GFR 45–90ml/min, mean: 61.4±3.7), 1,25(OH)₂D3 was positively (r=0.79,P<0.001) and iPTH inversely correlated (r=0.51, P<0.05)with 25(OH)D3. In each of nine such subjects studied, seasonalvariations in 1,25(OH)₂ (P<0.001) and PTH (P<0.05, 1-tailedtest), as well as in 25(OH)D3 and 24,25(OH)₂D3 were observed.We conclude that (1) 1,25(OH)₂D3 may be reduced early in thecourse of chronic renal failure and that (2) because of abnormaldependence of 1 ,25(OH)₂D3 on 25(OH)D3, low 25(OH)D3 may resultin reduced 1,25(OH)₂D3 values post transplant. Increased PTHin such cases suggests the functional significance of theseobservations.     

Subclinical pulmonary oedema and intermittent haemodialysis

It has been postulated that patients with chronic renal failure,even in the absence of cardiopulmonary symptoms, accumulateinterstitial pulmonary fluid, which is removed by haemodialysis.To test this hypothesis we used the indocyanine green (ICG)-heavywater double indicator dilution method to measure lung water,cardiac output, and central blood volume in relation to haemodialysis.Ten uraemic patients, without cardiopulmonary symptoms, wereinvestigated at the beginning and end, and 2 h after, a regulardialysis session. A group of 18 surgical patients about to undergoelective abdominal surgery served as controls. Despite normalgas exchange, central blood volume, and cardiac output at thestart of dialysis the mean (SD) lung water was significantlyhigher than in the control group [4.8 (0.9) compared with 3.6(0.7) ml/kg, P<0.001]. There was no correlation between weightgain between sessions of dialysis and the magnitude of lungwater at the start of dialysis. Lung water decreased (P <0.001)to the level of the control group in response to dialysis. Therewas no correlation between weight loss and reduction in lungwater induced by dialysis. In conclusion, we have verified thepresence of subclinical pulmonary oedema which was removed bydialysis in a group of patients with established renal failure.The variations in lung water cannot be explained by hydrostaticmechanisms alone.     

Aluminium-related osteodystrophy and desferrioxamine treatment: role of phosphorus

We investigated (1) the prevalence of aluminium overload among96 patients with symptomatic bone disease haemodialysed from1987 to 1989 in the Sao Paulo area, Brazil; (2) the effect of6 months desferrioxamine (DFO) treatment (1–2 g/week).All patients underwent a first bone biopsy. Aluminium overload(extent of stainable bone aluminium more than 20% trabecularsurface) was observed in 74 of 96 patients. Forty overloadedpatients were divided into patients with high bone formationrate (BFR) (group 1; n=17) and patients with low BFR (group2; n=23), and had a second biopsy after DFO therapy. In bothgroups aluminium surface was reduced after treatment (P<0.001),osteoblast surface (P<0.02-P<0.01) and plasma parathyroidhormone (iPTH) (P<0.01) increased. In group 1 BFR remainedhigh. In group 2 BFR remained low in 16 patients (2a) and increasedin seven (P<0.02) (2b). In group 2a plasma phosphorus wasbelow that in group 2b patients, before (P<0.03) and after(P<0.01) DFO. The histological features of group 2a patientsresembled hypophos-phataemic osteomalacia, those of group 2bpatients aluminium osteodystrophy. These data show a high prevalence of aluminium overload in Brazilianpatients. Low-dose DFO therapy was safe, decreased bone pain,prevented fractures, and reduced stainable bone aluminium. Bonelesions only partially improved, suggesting that low phosphorusintake and/or plasma calcitriol concentrations may have preventedimprovement of bone formation and mineralization.     

Reduced speed of sound in tibial bone of haemodialysed patients: association with serum PTH level

BACKGROUND: In end-stage renal disease, average bone mineral density hasbeen reported to be normal or only modestly reduced, more soin the cortical bone. The purpose of the present study was toexplore the potential use of quantitative ultrasound, a methodreflecting both quantitative and qualitative properties of bone,in assessing bone status in patients on maintenance haemodialysis. METHODS: We studied 71 patients (age 17–81 years, time on dialysis0–18 years). The speed of sound waves (tSOS; m/s) propagatingalong the cortical bone has been determined at the tibial shaft.tSOS results were expressed as Z scores, i.e. units of standarddeviations from age- and sex-matched normal mean values, andcorrelated with relevant clinical and biochemical variables. RESULTS: SOS Z score averaged –2.0 (range –6.8 to 0.6; P<0.001)and was negative in 93% of the patients. Significant inversecorrelations were found between SOS Z score and both time ondialysis (r=–0.52; P<0.0001) and serum PTH (r=–0.39;P=0.002). Markedly reduced SOS Z score, below –2, wasfound in 80% of the patients whose PTH levels exceeded 34 pmol/l(five times the upper normal limit), compared with 43% of thepatients whose PTH levels were below 34 pmol/l (P=0.04). Comparedto patients with out bone pain (n=51), subjects with bone pain(n=20) had somewhat lower SOS Z scores –2.5±2.0versus –1.8±1.4; n=0.08), but this could be accountedfor by longer time on dialysis. CONCLUSIONS: tSOS is substantially reduced in the majority of haemodialysedpatients and is related to time on dialysis and serum PTH level.The clinical value of this novel method needs further exploration.     

Plasma advanced glycosylation end-products in maintenance haemodialysis patients

BACKGROUND.: Pentosidine is a useful marker of advanced glycation end-products(AGE) which form cross-links between proteins and have beenfound elevated in plasma and tissues of uraemic and haemo-dialysedsubjects. The origin and fate of these molecules are not clearlyunderstood, but they might play a role in the cardiovascularcomplications of end stage renal failure. The aim of this studywas to evaluate the effect of different types of substitutivetherapy on the removal of pentosidine. METHODS.: Pentosidine was measured by a two-step HPLC methodology. Itsconcentration was evaluated in plasma before and after dialysissession, in 24-h urine, and in dialysate of subjects treatedwith three types of chronic substitutive therapy: bicarbonatehaemodialysis, acetate-free biofiltration, and haemofiltration.Pentosidine levels were compared among the three therapy modalitiesand correlated with clinical and biochemical parameters. RESULTS.: Plasma pentosidine level was extremely high (23.7±2.0pmol/mg protein) in the patients treated with the differentdialysis modalities. The dialysis session had no significanteffect on its plasma concentration, but haemofiltration seemedto be the most efficient method (300–2000 nmol of pentosidineremoved per session versus 250–700 nmol per session withthe two other approaches). An interesting correlation was foundbetween pentosidine and blood urea nitrogen (r=0.58, P<0.01)and pentosidine with uric acid (r=0.48, P<0.05). CONCLUSIONS.: These results suggest that none of the methodology showed agood removal of pentosidine, but among them haemofiltrationhas the best efficiency. The statistical relationships betweenpentosidine and urea and uric acid respectively might provideinsight into the origin of pentosidine. The accumulation ofreactive AGE in uraemic patients may be implicated in the organand tissue damage observed in uraemia.     

Atherogenic lipid profile and lipoprotein(a) in relation to serum albumin in haemodialysis patients

Malnutrition in haemodialysis patients is associated with anincreased cardiovascular mortality. Lipoprotein(a) (Lp(a)) isan independent risk factor for atherosclerotic cardiovasculardisease. To evaluate the relationship between atherogenic lipidprofile and serum albumin in haemodialysis patients we measuredfasting serum Lp(a), total cholesterol (TC), high-density lipoprotein-cholesterol(HDL-C), triglyceride (TG), apoprotein A-I (ApoA-I), apoproteinB (ApoB) and albumin in 101 haemodialysis patients and in 46healthy subjects as a control. The haemodialysis patients weredivided into two groups on the basis of the level of serum albumin:group I, serum albumin <4.0 g/dl; group II, serum albumin>4.0 g/dl. Haemodialysis patients as a whole (n=101, 17.1 mg/dl (10.3–30.9))had higher serum Lp(a) than normal subjects (n = 46, 10.5 mg/dl(3.3–24)) (P<0.05). Lp(a) in group I (n = 38, 27.1mg/dl (14.6-35.0)) was significantly higher than in group II(n = 63, 14.5mg/dl(7.7–21.7), P<0.005) and normal subjects(P<0.0005). However, serum Lp(a) level of group II was notdifferent from those of normal subjects. There was a significantinverse correlation between serum Lp(a) and albumin concentration(r_s = -0.26, P<0.01). TC, TG, HDL-C, ApoA-I, ApoB, TC/HDL-C,and ApoA-I/ApoB ratios were not different between group I andgroup II. No correlation was found between albumin and TC, TG,HDL-C, TC/HDL-C, and ApoA-I/ApoB ratios. These results suggest that Lp(a) could be responsible for anincreased cardiovascular mortality in haemodialysis patientswith malnutrition.     

Endothelin-1 in children with chronic renal failure

Endothelin-1 (ET-1) was meansured after extraction from plasma of normal adults (5.9±1.9 pg/ml,n=22), normal children (7.1±1.86 pg/ml,n=29), nonhaemodialysed children with chronic renal failure (CRF) (11.1±1.8 pg/ml),n=10), renal graft recipients (9.5±3.4 pg/ml,n=37), haemodialysed children 24 h after a haemodialysis session (20.02±10.9 pg/ml,n=26) and haemodialysed children before and after a haemodialysis session (15.31±10.6 and 13.8±8.5 respectively,n=14). A sensitive and specific radioimmunoassay was used. ET-1 was significantly higher in non-haemodialysed CRF children and in renal graft recipients than in normal children (P<0.001 andP<0.01, respectively) and significantly higher in haemodialysed children when compared with normal children, non-haemodialysed CRF children and renal graft recipients (P<0.001). ET-1 concentrations were similar in normal children and normal adults. ET-1 was inversely correlated with glomerular filtration rate in non-haemodialysed CRF children (r=–0.39,P<0.01) and positively correlated with extracellular volume in haemodialysed children (r=0.435,P<0.03). After haemodialysis, ET-1 increased in 6 and decreased in 8 of the 14 children studied before and after a haemodialysis session.     

Adequacy of dialysis and nutritional status in CAPD

Urea kinetic modelling (UKM) was used to assess adequacy ofdialysis in 50 CAPD patients. Nutritional status was assessedfrom the measurement of visceral protein status (total protein,albumin, transferrin, immunoglobulins, complement), somaticprotein status (anthropometry), and dietary intake (1 week weigheddietary inventory and normalized protein catabolic rate (NPCR)from UKM). Morbidity was assessed from the peritonitis and admissionhistory. Mean Kt/V (corrected to x3 weekly dialysis) was 0.66 ±0.02. Dietary protein intake estimated from the NPCR (1.08±0.03g kg^–1 day^–1) correlated well (r=0.72, P<0.001)with that estimated from the dietary inventory (1.10±0.04g kg^–1 day^–1). There was a strong correlation betweenKt/V and NPCR corrected for actual weight (r=0.65, P<0.001),but when NPCR was corrected for IBW this correlation was weaker(r=0.35, P<0.05). Patients were divided by Kt/V into twogroups (>0.65, n=22 and <0.65, n=28). There were no significantdifferences in the indices of visceral protein status betweenthe two groups. Weight, height, BMI, fat free mass and arm musclearea were significantly greater in the group Kt/V<0.65. Residualrenal function (creatinine clearance) was higher in the groupKt/V>0.65 (3.8±0.7 versus 1.9±0.5 1/24 h, P<0.05)and plasma creatinine less (913±51 versus 1265±51µmol/l, P<0.001). Hb, potassium, bicarbonate, phosphate,alkaline phosphatase, PTH, and blood pressure were not different.Neither was there any difference between the two groups in anyof the indices of morbidity.     

Effect of L-carnitine administration on erythropoietin use in thalassemic minor haemodialysis patients.

Sir, We read with great interest the recent letter by Arduini etal. [1], on the effect of L-carnitine (LC) on erythrocyte survivalin haemodialysis patients. In the same issue, there is a paperby Hothi et al. [2] showing that plasma free-carnitine (FC)levels fell from 26.54 ± 2.99 to 15.6 ± 2.34 µmol/l(P < 000.1) in nocturnal haemodialysis (NHD). A similar reductionin plasma acyl-carnitine (AC) levels was observed (from 13.22± 1.34 to 6.24 ± 1.20 µmol/l (P < 0.001)).The AC : FC ratio improved from 0.51     

Abnormal Blood Rheology in Progressive Renal Failure: A Factor in Non-immune Glomerular Injury?

Chronic renal insufficiency progresses by a final common pathwayof glomerular damage characterised by microvascular injury andglomerulosclerosis. In order to investigate the possible roleof blood rheology in this process, rheological indices werecompared between healthy controls and a group of patients withprogressive renal failure due to renal diseases that were notconsidered to be immunologically mediated. Plasma viscositywas significantly increased in the renal insufficiency group(P<0.005), and correlated with raised plasma concentrationsof fibrinogen (r=0.63; P<0.005). Whole-blood viscosity correctedto a standard haematocrit of 0.45 was also raised. A weak butsignificant correlation was seen between plasma viscosity and24-h urinary protein excretion (r=0.50; P<0.005). Our data show that in chronic renal insufficiency, rheologyis abnormal. Proteinuria correlates with plasma viscosity, whichis consistent with the hypothesis that raised plasma viscosityleads to an increase in glomerular capillary pressure and thenceglomerular permeability. Correction of rheological abnormalitiesmight help to preserve kidney function and reduce proteinuriain these patients.     

Survey of Blood Lead and Plasma Aluminium Concentrations in Patients of a Renal Unit

Blood lead and plasma aluminium concentrations have been measuredin patients with end-stage chronic renal failure treated byhaemodialysis (HD) or by continuous ambulatory peritoneal dialysis(CAPD) and in a control group of non-dialysed patients withchronic renal failure (CRF). Data on a group of subjects withnormal renal function is included for comparison. We have foundsignificantly increased mean blood lead and plasma aluminiumconcentrations in all patients with chronic renal failure comparedto a group with normal renal function. All blood lead concentrations were within the accepted safeexposure range of less than 1.8 µmol/l (380 µg/l)).There were significant differences among the patient groups:home HD, 0.60±0.25 µmol/l (124±52 µg/l);hospital HD, 0.39±0.31 µmol/l (81±64 µg/l);CAPD, 0.32±0.17 µmol/l (66±35 µg/l);CRF, 0.38±0.20 µmol/l (79±41 µg/l);normal, 0.24±0.11 µmol/l (50±23 µg/l).Correction of the blood lead results for haemoglobin accentuatesthese differences (i.e. hospital HD, 4.61±3.25 nmol/g(0.96±0.67 µg/g); CRF, 3.05±1.46 nmol/g(0.63±0.30 µg/g); normal, 1.65±0.70 nmol/g(0.34±0.14 µg/g). Plasma aluminium concentrations show a similar pattern: homeHD, 1.09±0.70 µmol/l (29.4±18.9 µg/l);hospital HD, 0.81±0.58 µmol/l (21.9±15.7µg/l); CAPD, 0.34±0.34 µmol/l (9.2±9.2µg/l); CRF, 0.18±0.09 µmol/l (4.9±2.4µg/l); normal, 0.09±0.07 µmol/1 (2.4±1.9µg/l). The duration of dialysis treatment is an important determinantof metal accumulation: there is a significant positive correlationbetween the duration of dialysis treatment and both blood lead:haemoglobinratio (r=0.48, P<0.01) and plasma aluminium (r=0.61, P<0.01)concentrations. There is also a significant negative correlation(r= –0.59, P<0.01) between urine volume and plasmaaluminium for haemodialysis patients, but not for peritonealdialysis patients. Urine volume shows no relationship to bloodlead. Age has no effect on lead accumulation in any of the patientgroups, but there is a significant correlation of age to bloodlead in the normal renal function group (r=0.47, P<0.01).The effect of sex and hypertension on metal concentrations isalso discussed. It is considered probable that the dialysate is a major factorcontributing to the accumulation of both elements. The possiblelong-term clinical significance of these findings remains tobe determined.