Enhanced platelet reactivity with erythropoietin but not following transfusion in dialysis patients

Although the haemostatic defects that occur in uraemia are complex,a major factor is the anaemia of renal failure. This may nowbe corrected by recombinant human erythropoietin (rHuEpo) therapyrather than by repeated blood transfusion. Platelet reactivityto shear stress and collagen was measured using non-anticoagulatedblood to study the effect of erythropoietin or blood transfusionon platelet function. Twenty dialysis patients were commencedon 25–50 U/kg rHuEpo twice weekly. The dose was adjustedafter 3 months to maintain target Hb 10–10.5 g/dl. A further15 patients were studied before and 10–12 days after receivingblood transfusion. Baseline platelet reactivity was subnormalin both groups versus control (P<0.0001). In the rHuEpo group,a significant increase in platelet reactivity was observed at2 months (P<0.005) which disappeared at 3 months. This wasnot related to the increase in Hb (7.3±0.3 to 10.2±0.3g/dl, P<0.0001). There was no change in platelet reactivityafter transfusion, despite an increase in Hb (6.2±0.2to 8.8±0.2 g/dl, P<0.0001) similar to that occurringin the rHuEpo group. We conclude that after rHuEpo therapy butnot after transfusion a transient increase in platelet reactivityoccurs which is dissociated from changes in platelet and redcell numbers.     

Low-dose aspirin does not prevent thrombovascular accidents in low-risk haemodialysis patients during treatment with recombinant human erythropoietin

Treatment of the anaemia of renal disease with recombinant humanerythropoietin results in an improvement of haemostasis andan increased risk of thrombovascular accidents. In this prospective,placebo-controlled, double-blind, and cross-over study, theeffects of low-dose acetylsalicylic acid (30 mg daily) on thromboticand bleeding events during the initial period of treatment witherythropoietin in anaemic haemodialysis patients without previousthrombovascular accidents or known increased risk for thrombosiswere investigated. During correction of the haematocrit andthe first 3 months thereafter, group A (n = 68) received placeboand group B (n = 69) 30 mg acetylsalicylic acid daily. Cross-overtook place after the 3rd month of a stable haematocrit. Thestudy ended 3 months later. Target haematocrit (30–35%) was reached in 12.4±8 weeks (M ± SD). In group A the bleeding time was 382±285s, decreasing to 282±208 before cross-over (P<0.0l),and increasing to 395±271 (P<0.05) there after. Ingroup B the bleeding time was 390±381 s, 406±267(NS), and 285±238 (P<0.05) respectively. Twenty-twothrombovascular accidents were seen (16%, 13 during acetylsalicylicacid and 9 during placebo, NS), including 17 fistula thromboses.The incidence of bleeding events was not significantly differentbetween regimens. In conclusion, erythropoietin treatment resulted in a reductionof the bleeding time. When 30 mg acetylsalicylic acid was takenduring the treatment, the bleeding time did not decrease. Theregimen did not result in an increased number of bleeding events,but neither were thrombovascular accidents prevented in low-riskpatients.     

A double-blind, randomized, placebo-controlled study of nifedipine on early renal allograft function

A double-blind, randomized, placebocontrolled study was conductedto determine the effect of nifedipine on early renal allograftfunction when added to a triple therapy immunosuppression regimecomprising low-dose cyclosporin (CsA), prednisolone and azathioprine.Fifty adult cadaveric renal allograft recipients were randomizedto placebo (group P n=17), nifedipine 10 mg preoperatively and20 mg b.d. postoperatively for 48 h, followed by matching placebofor 3 months (group NS n=16) or nifedipine 10 mg preoperativelyand 20 mg b.d. postoperatively for 3 months (group NL n=17).Donor and recipient exclusion criteria included recent calciumantagonist treatment. At 3 months after transplantation meanGFR adjusted for graft loss was significantly higher in groupNL than in NS (mean ± SD 61±28 versus 34 ±25 ml/min/1.73 m²; P<0.05), group P being intermediate (45± 34ml/min/1.73 m²). Similarly, effective renal bloodflow (ERBF) at 3 months was higher ingroup NL than in groupsP and NS (mean ± SD 351 ± 175 versus 216±166and 220±162 ml/min/ 1.73 m²; P<0.05). The differenceswere not significant by 6 months post-transplantation. Thisstudy suggests that oral nifedipine commenced preoperativelyand continued for 3 months following transplantation has beneficialeffects on early renal allograft function whenincorporated aspart of an immunotherapy regimen based on cyclosporin.     

Influence of ACE inhibition on glucose tolerance in patients with stable chronic renal failure

ACE inhibitors improve glucose tolerance and insulin sensitivityin hypertensive patients with normal renal function. Hypertensivepatients with renal failure are a high-risk group who are particularlyglucose intolerant and insulin resistant. We have thereforestudied whether ACE inhibition improve glucose tolerance inthis group as well. In a double-blind placebo-controlled crossover study 10 patientswith stable moderate chronic renal failure (mean endogenouscreatinine clearance 40±16 ml/ min/1.73 m² were examined.Patients were randomly allocated to receive either placebo orthe ACE inhibitor perindopril (2 mg/day per os) for 14 days.After 7 days of wash-out they received the alternative medicationsin random order for another 14 days. Before and after each ofthe two treatment periods (day 1 and day 15) an intravenousglucose tolerance test (i.v. GTT) with concomitant determinationof insulin levels was performed. The glucose disappearance rate(K value) was calculated to express changes in glucose tolerance.An i.v. GTT was also performed in a group of healthy volunteers. The mean K value was significantly (P<0.05) lower, i.e. glucosetolerance was impaired, in patients compared with healthy controls.In addition, baseline and peak insulin levels after the i.v.GTT were significantly higher (P<0.05) in patients than inhealthy subjects. The K values in patients before and afterplacebo treatment (1.33±0.31 and 1.41±0.45 respectively)were not significantly different from the values with perindopriltreatment (1.35±0.37 and 1.41±0.48 respectively).Furthermore, no significant differences between placebo andperindopril treatment were found with respect to the insulinresponse to the glucose load. The peak (5 min) insulin concentrationsafter the i.v. glucose load were 49.0±19.2 µU/ml(day 1) and 50.0±24.9 (day 15) with placebo and 49.2±19.3(day 1) and 46.8±17.9 (day 15) with perindopril. Finally,no significant differences between the two treatment periodswere observed with respect to serum lipid, HbA_1C, glucagon,potassium, and creatinine levels, whereas systolic blood pressuredecreased significantly with perindopril treatment. In contrast to hypertensive patients with normal renal function,ACE inhibition does not cause a demonstrable change of glucosetolerance in patients with moderate chronic renal failure.     

Late outcome of a controlled trial of enalapril treatment in progressive chronic renal failure. Hard end-points and influence of proteinuria

An earlier controlled trial showed that over an average of 26months, enalapril slowed the progression of chronic renal failure.Following completion of the trial, the patients continued toreceive antihypertensive treatment according to ordinary clinicalcriteria. All but four patients in the enalapril group remainedon that drug, and two patients in the control group were switchedto an angiotensin-converting enzyme (ACE) inhibitor. In thepresent study the fate of the 70 patients 44 months after terminationof the trial was investigated, with a total follow-up of around7 years. In the original enalapril group, 12 of the 35 patients(34%) were alive without renal replacement therapy versus fiveof the 35 patients (14%) in the control group. This differenceof 20% in favour of having been in the enalapril group in theoriginal trial was significant (P=0.05; 95% confidence limits0.5–39.5%). The influence of baseline proteinuria on clinical outcome wasanalysed. In the original control group, baseline renal clearancesof albumin (C_alb) and immunoglobulin G (C_IgG) were significantlylower in patients surviving without renal replacement therapyat follow-up than in patients who ultimately developed end-stagerenal failure (ESRF) (P<0.05). In the original enalaprilgroup, these baseline clearances were equal in the two renaloutcome groups. In all patients, baseline C_alb and C_IgG werenegatively correlated with the rate of change in GFR duringthe controlled trial (r=–0.37, P<0.01 and r=–0.28,P<0.05). In all patients alive without renal replacementtherapy at follow-up, independent of their original treatment,the initial (1–8 weeks) fractional Caib was 79% of baseline,significantly less than 100% in patients who ultimately developedESRF (P<0.05). Baseline total plasma cho lesterol was lowerin patients alive without replacement therapy, 5.8 (range, 4.5–8.8)as compared with 6.9 (4.4–12.7) mmol/l in patients withultimate ESRF (P<0.05) and 7.2 (5.3–9.2)mmol/l in patientswith non-renal death (P<0.05). The clinical outcome was notassociated with differences in baseline high-density lipoproteinor plasma triglyceride. These observations suggest that enalapril treatment improveslong-term dialysis-free survival in patients with progressivechronic renal failure. Renal function outcome appears to beinfluenced by the magnitude and type of proteinuria, the initialantiproteinuric response to treatment, and the plasma cholesterollevel.     

Modulation of platelet cytosolic calcium during erythropoietin therapy in uraemia

Erythropoietin therapy for uraemic anaemia is associated witha high rate of hypertensive and thrombotic complications. Themechanism is unknown, but a change in cellular calcium controlmay be relevant to changes in blood pressure and thrombosis. Platelets were utilized as a model of vascular smooth musclecells. The effects of erythropoietin therapy on platelet cellularcalcium, assessed by fura-2, were meas ured in 25 patients receivingrenal replacement therapy during a 6-month treatment period. Three patients failed to reach a target haemoglobin and wereexcluded from the analysis. Blood pressure increased in 11 ofthe remaining 22 subjects, eight requiring an increase in antihypertensivemedication. There were no differences in cellular calcium controlbetween the group in whom blood pressure rose and patients withstable blood pressure. Overall there was a fall of 24% in restingcytosolic calcium (baseline 69.2 ± 5.1 to 52.5 ±3.0 nmol/1, P<0.05) after 3 months of erythropoietin therapy.There was no change in the thrombin-stimulated peak responsein the presence of extracellular calcium during therapy, althoughthrombin-stimulated intracellular release also fell at 3 months(baseline 769±61 versus 3 months 559±49nmol/l,P<0.01 This study suggests that intracellular free calcium controlwithin platelets improves in response to erythropoietin therapy.However these changes appear not to be related to the developmentof hypertension.     

Influence of blood volume on the blood pressure of predialysis and peritoneal dialysis patients treated with erythropoietin

Twenty-seven patients with renal failure (16 on CAPD and 11predialysis) were treated with erythropoietin. At 12 weeks,the mean haemoglobin concentration (±SEM) in the CAPDpatients had increased from 7.07 ± 0.20 to 10.88 ±0.45 g/dl (two-tailed paired t test, P<0.0001) and in thepredialysis patients from 6.90 ±0.35 to 10.05 ±0.47 g/dl (P< 0.0001). Predialysis patients were taking moreantihypertensive medication at baseline. No increase was requiredin either group after erythropoietin; there was no change inblood pressure in the CAPD patients, though in the predialysispatients the systolic blood pressure rose slightly from 132to 146 mmHg (P=0.029) and the mean blood pressure from 95 to103 mmHg (P=0.028). In 12 patients (6 on CAPD and 6 predialysis) the red cell volume,plasma volume, and total blood volume were measured before andafter treatment. In the CAPD patients there was a marked expansionof the red cell volume from 912±127 to 1471±222ml (P=0.004) and a concomitant contraction of the plasma volumefrom 3932 ±250 to 3178 ±326 ml (P=0.005), leavingthe blood volume unchanged from 4843 ± 352 to 4649 ±503ml. Predialysis patients had a similar expansion of the redcell volume from 733 ± 59 to 1304± 161 ml (P=0.017)but no contraction of the plasma volume (from 3417 ±354to 3314 ±260 ml), so that the blood volume tended toexpand from 4149 ±347 to 4618 ±414 ml (P= 0.053).The mean contraction of the plasma volume in the predialysisgroup was trivial (– 102 ±214 ml), whereas in theCAPD group it was large (–754 ±158 ml, P=0.034,two-tailed unpaired t test). Thereby the predialysis group experiencedan expansion of the total blood volume of 469±186ml,whereas the CAPD group experienced a contraction of the bloodvolume of –195±189 ml(P=0.031). We conclude that (a) increased blood volume may contribute tothe exacerbation of hypertension induced by erythropoietin therapy;(b) gradual reduction of plasma volume, aiming for a stabletotal blood volume, is an important strategy for the preventionand control of erythropoietin-induced hypertension; (c) as reductionof plasma volume may be more problematic in predialysis patients,adequate blood pressure control may consequently be slightlymore difficult, placing more reliance on antihypertensive medication.     

High dose enalapril impairs the response to erythropoietin treatment in haemodialysis patients

Background: The resistence to recombinant human erythropoietin (rHuEpo) therapy in haemodialysis (HD) patients has multifactorial aetiologies; erythropoietin insufficiency, dialysis insufficiency, iron deficiency, and secondary hyperparathyroidism. Angiotensin-converting enzyme (ACE) inhibitors induce anaemia in patients with essential hypertension, congestive heart failure, chronic renal insufficiency, and renal transplants. Data exist suggesting that ACE inhibitors impair erythropoiesis in HD patients. Therefore the aim of this study was to investigate the impact of enalapril on rHuEpo requirement. Methods: In the present prospective non-randomized study of 12 months, we compared the effects of enalapril and nifedipine on rHuEpo requirement in 40 hypertensive patients receiving rHuEpo for more than 6 months on maintenance haemodialysis. Twenty normotensive rHuEpo-dependent patients served as a control group. All patients with severe hyperparathyroidism or iron deficiency were excluded. The mean (±SD) haemoglobin concentration was >10 g/dl in all groups. The mean weekly rHuEpo dose increased in the enalapril group (P<0.0001 vs before) and remained constant in the nifedipine and control groups (P=NS vs before). Statistically, there was no differences with regard to iPTH levels, dialysis parameters, iron status, and underlying renal diseases among all groups. Conclusion: High-dose enalapril increases rHuEpo requirement and should be reserved for dialysis patients with hypertension uncontrollable with other antihypertensive medications or dialysis patients with cardiac failure.     

ACE inhibition reduces proteinuria in normotensive patients with IgA nephropathy: a multicentre, randomized, placebo-controlled study

A multicentre, randomized, placebo-controlled study was performedin 39 adult patients with biopsy-proven IgA nephropathy withthe aim of comparing the effects of the ACE inhibitor fosinopriland placebo on proteinuria. All patients had normal blood pressureand normal renal function. Proteinuria ranged from 1.0 to 2.5g/24 h. After a 3-month run-in period, fosinopril and placebowere randomly administered in two 4-month sequences separatedfrom crossover treatment by a 1-month interval. The mean valuesof creatinine clearance did not change during either the placeboor the treatment sequences. The mean values of mean arterialpressure (MAP) were significantly lower during the fosinoprilsequence (90.4 ±9.0 mmHg) than in basal conditions (92.8± 9.1 mmHg) (P=0.034). The mean basal values of proteinuriawere 1.74 ±0.84 g/24 h. They were unchanged during theplacebo sequence (1.79 ±1.20) and fell to 1.37 ±0.98g/24 h after 4 months of fosinopril treatment. Using a multivariatestatistical analysis, the treatment effect by time on proteinuriawas significantly evident only in the fosinopril sequence (Wilkstest, P=O.O33). Changes in protein excretion were not correlatedwith changes in MAP, baseline plasma renin activity, and urinarysodium excretion. This controlled study shows that fosinoprilcan significantly reduce proteinuria even in normotensive patientswith IgA nephropathy. Obviously, the results of treatment withACE inhibitors on long-term renal prognosis remain to be elucidated.     

Human Recombinant Erythropoietin in Anaemic Patients on Maintenance Haemodialysis. Secondary effects of the Increase of Haemoglobin

Twelve anaemic patients on haemodialysis were treated with recombinanthuman erythropoietin, starting with 72 IU/kg/week. The dosewas doubled after 2 weeks until an increase of 2 g/dl of haemoglobinwas observed. The effects on various parameters were studiedduring a 3-month period. Haemogiobin increased from 6.70±0.74to l0.49±1.04g/dl (mean±SD, P<0.00l), potassiumfrom 5.51±0.50 to 6.06±0.65mmol/1 (P<0.005),phosphate from 1.78±0.40 to 2.17±0.4Ommol/1 (P<0.001)and the calcium phosphorus product from 4.3 to 5.2 (P<0.001)Three patients developed marked periarticular inflammation dueto calcified deposits with a high calcium-phosphorus productof 6.8. An increase in arterial blood pressure was observedin three previously well-controlled hypertensive patients, oneof whom developed hypertensive encephalopathy. We conclude thatrecombinant human erythropoietin is very effective in treatingthe anaemia of end-stage renal failure on haemodialysis. Regularestimations of serum potassium and phosphate are mandatory.In hypertensive individuals a further increase in blood pressureis possible.     

Correlation between glomerular morphology and renal haemodynamic response to amino-acid administration in patients with IgA nephropathy

RATIONALE.: To establish relationship, if any, between renal morphologyand renal haemodynamic response to amino acids. DESIGN AND METHODS.: We investigated the correlation between renal haemodynamic regulationand morphology in a group of 15 patients with primary IgA nephropathy(IgAN) (age 26±2 years, BMI 24.4±1, GFR 64±5ml/min, RPF 377±34 mI/mm, FF 0.17±0.02). Twelvenormal subjects (age 30±3 years, BMI 24±1, GFR82±6 ml/min, RPF421±42 ml/min, FF 0.19±0.02)were studied as controls. IgA patients were divided into twogroups according to the histological staging of glomerular lesions:group I (n=7) stage II, and group II (n=8) stage III–IV. RESULTS.: In the basal state GFR was similar in the two groups and averaged64±9 and 64±6 ml/mm respectively. In contrast,FF was significantly lower in group II(0.14±0.01) (P<0.05)in comparison to group I (0.21±0.03) and controls (0.19±0.02).In order to evaluate the renal functional reserve, all studygroups underwent to an intravenous amino-acid infusion designedto increase plasma amino acid levels twofold (total from 2096±145to 4301±221 µmol/l in IgA nephropathy patientsand from 2272±83 to 3844±238 µmol/l in controls).In response to amino-acid infusion, GFR rose significantly ingroup I (GFR 20±2% and RPF 37±4% versus basal)and controls (GFR 20±2% and RPF 20±3% versus basal)(both P<0.01 vs basal). In contrast, in patients with moresevere glomerular lesions (group II) neither GFR nor RPF rosesignificantly (GFR –1±4% and RPF –8±6%versus basal) (P NS versus basal, P<0.01 versus group I andcontrols). CONCLUSIONS.: The data show that in IgA nephropathy: severe forms of glomerularlesions are associated with a complex alteration of glomerularhaemodynamic regulation, characterized by lower basal FF andloss of haemodynamic response to hyperaminoacidaemia.     

Idiopathic membranous nephropathy in the elderly

In this retrospective non-randomized study we reviewed the outcomefor 41 patients with membranous nephropathy older than 65 yearsat onset and followed for at least 1 year. Twelve of the patientsnever received any specific treatment (group A), 15 were treatedwith a 6-month course of methylpredniso-lone alternated to chlorambucilevery other month (group B), and 14 received corticosteroidsalone for 3–12 months (group C). At the end of a meanfollow-up of 92±61 months in group A, 53±35 ingroup B, and 38±25 in group C there were significantlymore remissions of nephrotic syndrome in group B than in groupA (P=0.035) or in group C (P = 0.010). Moreover patients ingroup B spent a significantly longer period without nephroticsyndrome than patients in group A (P=0.000) and C (P=0.000).Three patients in group A and one in group B died. During thefollow-up six patients of group A, two of group B, and fiveof group C developed renal function deterioration. In patientsfollowed for at least 5 years the mean plasma creatinine increasedfrom a basal of 112±29 to 239±287 µmol/lat the 5th year in group A and from 113±14 to 124±30µmol/l in group B. The mean urine protein excretion remainedunchanged in group A (basal 4.6±2.3 versus 4.8±5.7g/day at 5 years) while it decreased in group B (from a basalof 6.8±3.5 to 1.1±0.4 g/day at 5 years). The natural course of membranous nephropathy in older patientsis similar to that of patients of the second age. Corticosteroidsalone do not modify the outcome. Corticosteroids alternatedwith chlorambucil seem to improve the chances of remission andto protect from renal dysfunction, but elderly patients aremore exposed to the side-effects of this regimen. Thus thistreatment should be limited to patients with severe nephroticsyndrome and/or incipient renal insufficiency, using some particularcautions.     

Diabetic nephropathy and pregnancy: the effect of ACE inhibitors prior to pregnancy on fetomaternal outcome

BACKGROUND: Diabetic nephropathy is associated with an increase in perinatalmortality and morbidity in uncontrolled pregnant patients. Recentlyangiotensin converting enzyme inhibitor (ACE-I) was shown toimprove the disease status in non-pregnant subjects. The purpose of this study was to examine the effect of prepregnancytreatment of insulin-dependent diabetes mellitus (IDDM) nephroticwomen with captopril angiotensin converting enzyme inhibitor(ACE-I), on maternal renal function throughout pregnancy andon the fetomaternal outcome. METHODS: Eight IDDM nephrotic patients planning pregnancy were treatedwith captopril for a minimum of 6 months prior to conceptiontogether with intensive insulin management. Conception was allowedwhen proteinuria was <500 mg/day and euglycaemia was achieved.At conception captopril was discontinued. RESULTS: At the beginning of captopril treatment, proteinuria was 1633±666mg/day. At conception, proteinuria dropped to 273±146mg/day (P=0.0000) and increased gradually over the three trimestersto 593±515, 783±813, and 1000±1185mg/dayrespectively (P=0.2 between the trimesters); declining to 619±411mg/day (P=0.0002 vs conception) 3 months after delivery. Onlyin two patients (25%) did proteinuria exceed 1000 mg/day duringpregnancy. There was no significant change in any of the otherrenal function tests: CCT, serum creatinine, uric acid, K⁺ andblood pressure. However, there were three cases of PET justprior to delivery. Maternal glycaemic control improved significantlyprior to conception (P= 0.002) and remained euglycaemic (reflectedby daily glucose profile, HbA1C and fructosamine) throughoutgestation. Perinatal outcome was excellent.     

Effect of Nifedipine in the Protection of Renal Function During In Situ Preservation

In an experimental study on six healthy dogs both kidneys wereexposed and subjected to 1 h of ischaemia by clamping both renalvessels. To the left renal artery, 300 ml of cold (4°C)Euro-Collins solution in which nifedipine (Bay a 1040—20µg/kg per min) was diluted, was infused for 15 min. Simultaneously300ml of cold Euro-Collins solution plus 20 µg/kg permin of placebo (Bay a 1040—placebo) was infused in theright renal artery. The 1 h of ischaemia was divided in a 15-minperiod of cold ischaemia and 45 min of warm ischaemia, at theend of which both clamps were removed. During the 2 h (4x30min) following the removal of the clamps, urine volume, ureaand creatinine clearances, urine sodium concentration, sodiumfractional excretion (%) and urine/plasma osmolality ratio measurementswere made and results compared to the pre-ischaemia values.Both kidneys were then removed for histological study. The nifedipine group restored diuresis of 0.43±0.23 ml/minwithin 30 min, while this degree of diuresis (0.64±0.16ml/min) was achieved by the placebo group at 120 min. Urinevolume as well as creatinine and urea clearances of the nifedipinegroup were significantly higher in all studied periods comparedto the placebo group (P<0.01 or P<0.025). Urine sodiumand FE_Na (%) were not different between the two groups, andurine/plasma osmolality ratio was above 1.1 in all studied periodsfor both groups. The microscopic study did not show any significantdifferences between the two groups. We conclude that nifedipineis effective in the protection of renal function when it isadministered during experimental in situ preservation.     

Low-dose simvastatin is safe in hyperlipidaemic renal transplant patients

Hyperlipidaemia is common after renal transplantation, and becauseof its association with atherosclerosis, interest has increasedin the use of lipid-lowering drugs in transplant patients. Dietaryapproaches have not been consistently successful, and multiplepharmacotherapy and drug interactions have led to difficultiesin establishing lipid-lowering drug regimes. The statins reduceplasma cholesterol by inhibiting the rate-limiting step in cholesterolsynthesis, and although some side-effects have been reportedin their use after transplantation, the efficacy and safetyof low doses has not been formally established. A randomized single-blind placebo crossover study designed todetermine the safety and effectiveness of simvastatin in a singledaily 5-mg evening dose was therefore conducted in 26 stablerenal transplant patients, 14 of whom were receiving cyclosporinA. The results demonstrated no difference between total cholesterollevels in the baseline simvastatin and placebo periods: 7.97± 1.2 and 7.59±1.5 mmol/l respectively. After8 weeks of simvastatin, the total cholesterol declined significantlyto 6.72±0.87 mmol/l (P<0.001). A significant differencewas found when the placebo and simvastatin cholesterol levelswere compared at 4 and 8 weeks (P<0.01). LDL cholesterol decreased from 4.74 ± 0.87 to 3.78 ±0.78 mmol/l after 8 weeks on simvastatin (P<0.001), and apoB fell from 142 ± 31 to 112 ± 22 mg/dl (P<0.001).The difference in LDL cholesterol and apo B after 8 weeks ofsimvastatin when compared with the corresponding values on placebowas also significant (P<0.01). A slight but not significantincrement in HDL cholesterol from 1.10 ± 0.47 to 1.13± 55 mmol/l (NS) was seen after 8 weeks on simvastatin. Triglycerides and serum creatinine did not change during thestudy in any of the groups. Creatine kinase (CK.) remained inthe normal range (0–200 U/l), except for one patient nottaking cyclosporin who had a CK value slightly above the upperlimit of normal during the simvastatin period, without abnormalclinical signs. Repeated cyclosporin measurements remained withinthe therapeutic range (50–150 ng/ml). These results suggestthat low-dose simvastatin is effective and safe in reducingtotal cholesterol and LDL cholesterol in renal transplant patients.     

Recombinant human erythropoietin corrects anaemia during the first weeks after renal transplantation: a randomized prospective study

BACKGROUND.: Studies on the effect of recombinant human erythropoietin (rHuEpo)on haematopoiesis in patients with kidney transplants, havebeen limited to progressive chronic graft failure, late aftertransplantation. In the present prospective randomized study,the efficacy of rHuEpo in the correction of anaemia during thefirst weeks after renal transplantation (RTP) was evaluated. METHODS.: Patients were allocated to either an Epo-(n=14) or a non-Epo-treatedgroup (n=15). Epo (150 U/kg.week s.c.) was started at a haematocrit(Hct) <30% and was increased at weekly intervals by 30 U/kg.week,as long as Hct remained <25%. RESULTS.: In the Epo group, Hct increased from a nadir of 22±4%2 weeks after RTP to 30±4% at week 4 and to 36±4%at week 6 (P<0.001 and P<0.0001 respectively vs week 2).Corresponding values in the non-Epo group were 25±6%,28±6% (P=NS) and 32±6% (P<0.05 vs week 2) (overallevolution Epo vs non-Epo: P=0.038 by variance analysis). Thedifferences in Hct between the Epo and non Epo group were evenmore marked in patients without major complications (varianceanalysis P=0.009). The Epotreated patients required fewer post-surgicalblood transfusions (0.005 vs 0.014/days follow-up, P<0.05),in spite of greater post-surgical blood losses, especially atday 1 (P<0.05) and the presence of more major complications(7 vs 4) and a higher number of ganciclo vir-treated patients(4 vs 0; P<0.05). The maximum Epo dose after RTP was >2xhigher than the one required before RTP (197.1±45.1 vs85.0±76.0 U/kg.week; P<0.05). CONCLUSIONS.: It is concluded that rHuEpo during the first weeks after RTPis of benefit in the correction of the Hct in the early post-surgicalperiod, in spite of relative Epo resistance.     

Bilateral nephrectomy simultaneously with renal allografting does not alleviate hypertension 3 months following living-donor transplantation

Severe hypertension prior to renal transplantation has traditionallybeen an indication for bilateral nephrectomy. The reasons forhypertension after successful renal transplantation are howevermany, and the impact of simultaneous bilateral nephrectomy (BN)in this setting has not been well documented. We retrospectivelyevaluated 158 living-donor renal graft recipients. BN had beenperformed in 76 patients at the time of the transplantationand 82 were not nephrectomized (controls). All received a tripleimmunosuppressive drug regimen. Before transplantation, patientsin the BN group used 1.8±0.9 (mean±SD) antihypertensivedrugs/day, significantly more than in the control group (1.3±0.8;P<0.05). Three months after renal transplantation no differencewas found (0.9±1.0 drugs/day in the BN group vs 1.0±0.8drugs/day in the control group). No difference was found withrespect to serum creatinine, whole blood cyclosporin A (CsA)concentration or blood pressure between the groups. The numberof blood transfusions during the first week after transplantationwas significantly increased in the BN group (66 SAG units vs4 SAG units). The median hospitalization length was also longerin the BN group (21 days vs 16 days). In order to circumscribethe pre-transplant difference in use of antihypertensive medicationwe studied a subgroup of 62 hypertensive recipients (BN/control= 31/31) matched for number of antihypertensive drugs at thetime of transplantation (2.3±0.5 drugs/day in the BNgroup, 2.1±0.3 drugs/day in the control group). Threemonths after transplantation the use of antihypertensive drugsremained the same in the two groups (1.3±1.0 drugs/dayin the BN group vs 1.3±0.9 drugs/day in the control group).At 3 months no difference was found between the two hypertensivesubgroups regarding serum creatinine, whole blood CsA and haemoglobinconcentration or systolic blood pressure. However, the BN patientswere younger than the control group (38±10 years vs 49±11years, P<0.05) and this may explain the marginally lowerdiastolic blood pressure observed in the BN group (82±10mmHg vs 87±7 mmHg, P<0.05). It is concluded that,in recipients of living-donor grafts, bilateral nephrectomyperformed at the time of transplantation did not influence thenumber of antihypertensive drugs used 3 months after a successfultransplantation. Bilateral nephrectomy did however increasethe need of blood transfusions during the first week after transplantationand also the hospitalization length.     

Lack of renoprotective effect of i.v. N-acetylcysteine in patients with chronic renal failure undergoing cardiac surgery

Background. Pre-existing chronic renal failure is a significantrisk factor for acute renal failure (ARF) after cardiac surgery.N-acetylcysteine (NAC) has been shown to prevent contrast media-inducedARF. Our objective was to evaluate whether i.v. NAC has renoprotectiveeffects in patients with mild renal failure undergoing cardiacsurgery. Methods. In this prospective, randomized, double-blind study,80 patients with mild to moderate renal failure undergoing electiveheart surgery with cardiopulmonary bypass were recruited. Allreceived either i.v. NAC (n=38) or placebo (n=39) at inductionof anaesthesia and then up to 20 h. Urine N-acetyl-ß-D-glucosaminidase(NAG) and urine creatinine ratio, plasma creatinine, and serumcystatin C levels indicated renal function. Results. Levels of urinary NAG/creatinine ratio, plasma creatinineand serum cystatin C did not significantly differ between NACand placebo groups during five postoperative days. Urine NAG/creatinineratio increased over 30% in 100% of patients in the NAC groupvs 92.3% in the placebo group (P=0.081). Plasma creatinine increasedby 25% from baseline or over 44 µmol litre^–1 in42.1% in NAC group vs 48.7% in placebo group (P=0.560). Serumcystatin C exceeded 1.4 mg litre^–1 in 78.9% in NAC groupvs 61.5% in placebo group (P=0.096). Conclusions. Prophylactic treatment with i.v. N-acetylcysteinehad no renoprotective effect in patients with pre-existing renalfailure undergoing cardiac surgery.     

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.