Serum lipoprotein (a) concentrations in patients undergoing continuous ambulatory peritoneal dialysis

Lipoprotein (a) is a subspecies of low-density lipoprotein whichpossesses as part of its protein moiety a mutant form of plasminogentermed apolipo-protein (a), and which may be closely relatedto the risk of ischaemic heart disease and cerebral infarction.We have investigated the serum concentrations of lipoprotein(a) and other lipoproteins in 24 male patients on CAPD and comparedthem to healthy men (n= 100) and to age-matched healthy controls(n=38). The most striking finding was a substantial elevationof serum lipoprotein (a) in CAPD patients in whom it was 46.9(2.2–168) mg/dl (median and range) compared to 9.0 (<0.6–87.4)mg/dl in healthy control group and 6.7 (< 0.6–84.2)mg/dl in age-matched controls (both P<0.001). Patients, whencompared to healthy men, also had significantly increased serumtriglycerides (median and range, 1.94 (0.55–8.00) versus1.24 (0.36–4.40) mmol/1; P< 0.001), very-low-densitylipoprotein cholesterol (median and range, 0.98 (0.10–3.71)versus 0.46 (0.10–1.17) mmol/l; P<0.001), and lower-high-densitylipoprotein cholesterol (mean±1 sd, 1.26±0.29versus 1.35±0.31 mmol/l). Of these, however, only thedifference in very-low-density lipoprotein cholesterol remainedstatistically significant (P< 0.001) in comparison to age-matchedcontrols. The marked elevation of serum lipoprotein (a) in patientson CAPD may be due to increased hepatic synthesis as a consequenceof the substantial amounts of plasma proteins lost in the dialysate.Elevated serum lipoprotein (a) concentrations in CAPD patientsmay contribute to their risk of coronary artery disease.     

Hyperhomocysteinaemia: a significant risk factor for cardiovascular disease in renal transplant recipients

Moderate hyperhomocysteinaemia has been shown to constitutean independent risk factor for cardiovascular disease (CVD),a frequent cause of morbidity and mortality in renal transplantrecipients (RTR). In these patients few data regarding bothtotal homocysteine levels and their influence on cardiovas cularrisk have been reported. We therefore studied serum homocysteinelevels in deep-frozen sera from 42 kidney transplant recipientswith a follow-up of 11±4.5 years (mean±SD) aftertransplantation. Eighteen patients had one or more ischaemicevents (CVD(+)) and 24 patients had none (CVD(–)). Serumsamples had been drawn 1–6 months prior to the first vascularevent in CVD(+) patients and serum storage time was comparablein both CVD(–) and CVD(+) patients. Serum homocysteinelevels were measured using a radioenzymatic method. Mean homocysteinelevel was significantly higher in 42 RTR males and females (15.5±6.3,13.5±5.5 µM respectively) compared with 35 controlsubjects matched for age and sex (8.7± 1.9, 7.5±l.9µP<0.001). The difference in serum homocysteine levelsbetween CVD(+) and CVD(–) RTR nearly reached statisticalsignificance in male patients (18.6±7.8 versus 13.1 ±3.4µM, P<0.06) but not in female patients (P=NS). In theCVD(+) group 11/18 patients had homocysteine levels > 14µM (the upper limit in healthy controls) versus 7/24 inthe CVD(–) group (P=0.04). In these patients we simultaneouslymeasured in the same serum samples, serum triglycerides, andtotal and HDL cholesterol, and calculated LDL cholesterol. Bystepwise discriminant analysis and by logistic regression analysisin this relatively small patient population, only serum triglyceridesand homocysteine were selected as risk factors associated withCVD. We conclude that signi ficant hyperhomocysteinaemia ispresent in renal transplant recipients and represents a potentialrisk factor for cadiovascular disease in these patients.     

Monitoring of iron requirements in renal patients on erythropoietin

We studied 38 patients (9 haemodialysis, 18 peritoneal dialysis,11 advanced renal failure) over the first 12 weeks of erythropoietintherapy. In 14 iron-overloaded patients (ferritin >500 µg/l)the haemoglobin (±SEM) increased from 6.74±0.27to 9.85±0.36 g/dl (P<0.0001) entirely by mobilizingiron reserves (reduced from 1,220±73 to 739±111mg, P<0.0001). In the 24 non-overloaded patients (ferritin<500µg/l) the haemoglobin rose similarly from 7.04±0.18to 10.70±0.36 g/dl (P<0.0001), partly from iron reserves(depleted from 200±74 to –44±77mg, P=0.016)and partly from oral iron supplements (305±110 mg). Inthe overloaded patients the ferritin declined from 1057 µg/l(geometric mean, range 504–3699) to 317 µg/l (42–1505,P<0.0001). In the non-overloaded patients it declined from82 µg/l (8–461) to 45 µg/l (5–379, P=0.016).The transferrin saturation (TS) in the overloaded patients appearedto decline from 38.3±7.2% to 24.0±3.7% but thiswas not statistically significant. In the non-overloaded theTS was unchanged (23.3±2.4 before and 28.1±3.6%after treatment). Considering all 38 patients together, thehaemoglobin correlated negatively with the ferritin (r=0.3731,P<0.001) but not with the TS. The TS correlated with theserum ferritin initially (r=0.75, P<0.001) but not afterthe first 4 weeks. At 12 weeks, eight of 15 patients with irondeficiency (ferritin<50 µg/l) had a TS >20%, whereastwo of five patients with persistent iron overload (ferritin>500 µg/l) had a TS <20%. We conclude that (a) inpatients with iron overload, stored iron is utilizable for erythropoiesis;(b) oral iron supplements are necessary and sufficient for mostpatients without iron overload; (c) the serum ferritin is abetter indicator of iron status than the TS for renal patientson erythropoietin.     

Excellent uricosuric efficacy of benzbromarone in cyclosporin-A-treated renal transplant patients: a prospective study

Patients on cyclosporin A (CsA) often develop hyperuricaemiaand gout. In transplant patients the use of uricosuric drugsfor treating hyperuricaemia may be preferable to allopurinolbecause of the known interaction of the latter with azathioprine.We therefore prospectively studied the uricosuric efficacy of100 mg benzbromarone (Bbr;Desuric®) daily in 25 CsA-treatedrenal transplant patients with stable graft function and hyperuricaemia(>359 µmol/l for females, >491 µmol/l formales). Benzbromarone decreased plasma uric acid from 579±18µmol/l to 313±24 µmol/l (mean±SEM;P<0.001) and thereby normalized plasma uric acid in 21 of25 patients. The remaining four patients had creatininc clearancesbetween 21 and 25 ml/min, the lowest of the entire study group.Mean fractional clearance of uric acid increased from 5.4±0.4%to 17.2±1.0% (P<0.001). The relative decrease of plasmauric acid closely correlated with baseline creatinine clearance(r=0.67; P<0.001). CsA trough values were not influenced.None of the patients experienced any significant side-effects.As an unexpected find-ing, urinary uric acid excretion increasedfrom 2082 ± 175 µmol7sol;24 h to 3233 ±232µmol/24 h after 4 weeks' treatment with benzbromarone. In conclusion, benzbromarone normalized plasma uric acid inall CsA-treated renal transplant recipients with a creatinineclearance >25 ml/min. Due to its excellent efficacy and lackof significant side-effects, benzbromarone appears to be preferableto allopurinol in CsA-treated renal transplant recipients witha creati nine clearance over 25 ml/min.     

Fish oil and cyclosporin A-induced renal hypoperfusion in kidney-transplanted patients

BACKGROUND.: Dietary supplementation with fish oil has been said to improverenal function in cyclosporin A (CsA)-treated subjects. METHODS.: Renal function and the acute renal haemo-dynamic and tubularresponse to an oral CsA-dose (3 mg/kg) were investigated beforeand after 12 weeks of fish oil supplementation (6 g/day) in12 low-dose CsA-treated kidney-transplanted patients (s-creatinine,124 ± 24 µmol/l, mean ± SD). After an overnightfast, ten 1-h renal clearance periods were performed, two periodsbefore and eight after CsA-ingestion. An additional controlclearance study without CsA intake was performed in six subjects. RESULTS.: Fish oil did not change baseline values of the effective renalplasma flow (ERPF) or the glomerular filtration rate (GFR).Compared to the control study, CsA decreased GFR and ERPF significantlyon aver-age 20 ± 3% (P<0.01) and 23 ± 3% (P<0.01)respectively, 4–6 h after peak CsA blood concentrationwith no additional effect of fish oil. CsA also significantlydecreased the renal clearance of lithium, used as an index ofproximal tubular outflow, with no impact of dietary fish oil. CONCLUSION.: Fish oil supplementation had no effect on baseline renal functionor CsA-induced hypoperfusion in stable renal transplant recipientstreated with a low maintenance dose of CsA.     

Substitution of conventional cyclosporin with a new microemulsion formulation in renal transplant patients: results after 1 year

BACKGROUND: A new galenic form of cyciosporin A has been developed, basedon microemulsion technology. The bioavailability of the compoundis reiativeiy independent of food intake and bile flow. It wasthe purpose of this prospective clinical trial to study thesafety of the microemulsion form of cyclosporin A. METHODS: Three hundred and two renal transplant patients, stratifiedaccording to transplant age, were switched from the conventionalto the new micro-emulsion formulation of cyclosporin A. A 1:1conversion ratio was used. Measurements included CsA levels,S-creatinine, liver enzymes, uric acid, and blood pressure.Measurements were performed at baseline and on days 4, 8, 15,29 and months 3, 6 and 12 after conversion. Dose adjustmentswere performed to achieve trough levels of 80–120 ng/ml. RESULTS: Within the 12-month observation period the cyclosporin dosewas reduced by 14.7% (from 204±60 mg/day at baselineto 174±51 mg/day after conversion, P<0.001). Acutely,i.e. by day 8, a 1:1 dose conversion resulted in a modest increaseof mean drug trough levels (from 114 ng/ml at baseline to 120ng/ml, P<0.01). This increase was accompanied by an increasein serum creatinine concentration, a decrease in calculatedcreatinine clearance, and an increase in uric acid values (P0.05).Liver enzymes remained unchanged while systolic and mean arterialblood pressure decreased (P<0.05). After 1 month, drug troughlevels had decreased to baseline (112 ng/ml) and remained thereuntil month 6. They were significantly lower after 12 months(102±33 ng/ml, P<0.001). Creatinine clearance valuesincreased to above baseline at 6 and 12 months. Within the 1-yearperiod there occurred 24 (=8%) episodes of biopsy-proven rejectionand seven episodes of cyclosporin-attributed nephrotoxicity. CONCLUSIONS: The 1:1 conversion from conventional cyclosporin A to the microemulsionformulation is efficacious and safe, but an initial dose reductionof 10% is advised in patients with trough levels in the high-normalrange.     

Calcium balance and intact PTH variations during haemodiafiltration

BACKGROUND.: Recent approaches to prevent and treat secondary hyperparathyroidismin dialysis patients include decreasing dialysate Ca contentfrom 1.75 to 1.5 mM or lower. We have recently observed thatby decreasing dialysate Ca to 1.25 mM a rise in intact parathormoneserum levels occurs despite adequately controlled predialysisCa and phosphate serum levels. In that study complementary treatmentwith high-dose 1(OH) vitamin D3 was required to suppress theparathormone. In the present study we aimed to assess the totalCa balance as well as the modifications in parathormone inducedby the dialysis session in order to understand the reasons forwhich the rise in parathormone was induced. METHODS.: Fourteen HD patients treated with haemodi-afiltration threetimes/week gave their informed consent for the study. They weredistributed in two groups with identical treatment but for thedialysate Ca content which was 1.5 and 1.25 mM respectivelyand for the amount of oral CaCO₃ received. Total and ionizedCa, phosphate, pH, and albumin as well as parathormone weremeasured in serum before and after dialysis and in the spentdialysate during two dialysis sessions. RESULTS.: Serum ionized Ca (normalized to pH 7.4) did not change during1.25 mM dialysate Ca and significantly increased with 1.5mM(P<0.001). The end-dialysis values being 1.25±0.02and 1.38±0.02 mM respectively. Total Ca significantlydecreased with 1.25mM dialysate Ca (P<0.04) and increasedwith 1.5mM (P<0.003), the end-dialysis values being 2.51±0.03and 2.75±0.04mM respectively. In the dialysate the differencein ionized Ca concentrations, fresh minus spent dialysate was–1.78±1.12 mmol/l (NS) and 4.26±1.47 mmol/l(P<0.02) respectively for 1.25 and 1.5 mM dialysate Ca. Thedifference in total Ca concentrations, fresh minus spent dialysatewas –0.1±0.01 mmol/l (P<0.005 and –0.002±0.01 mmol/l (NS) respectively. Phosphate removal was higherin 1.25 mM dialysate-Ca-treated patients (40.4±1.75 mmol/sessionversus 34±1.3 mmol/session respectively, P<0.015).The use of 1.25 mM dialysate Ca did not result in a change inserum parathormone, while the use of 1.5 mM resulted in a decreaseof 43±15% (P<0.02) in patients with marked hyperparathyroidism. CONCLUSIONS.: Our data remind us of the difficulty in assessing Ca balancesand identifies the phosphate content as one of the factors influencingthe amount of ionized Ca in the dialysate. Although the long-termparathormone increase we observed using 1.25 mM dialysate Camay well not be explained only by the acute intradialytic modifications,the negative Ca balance identified here (which was missed withthe analysis of ionized Ca alone), and the lack of parathormoneinhibition may participate in the relapse of hyperparathyroidism.     

Effect of gastric acid secretion on intestinal phosphate and calcium absorption in normal subjects

BACKGROUND.: Phosphate-induced hyperparathyroidism still represents an intriguingproblem in dialysis patients. Postprandial hyperphosphataemiais considered to be the main stimulus to parathyroid hyperfunction,and therefore many efforts have focused on the use of phosphatebinders to prevent phosphate absorption. METHODS.: We investigated whether the pH-mediated gastric ionization ofcalcium phosphate dietary salts is necessary for its intestinalabsorption. In eight normal subjects we measured 24-h urinarycalcium phosphate excretion and the postprandial blood calciumphosphate profile after a meal containing 1 g of calcium and2 g of phosphate salts in a crossover placeboomeprazole study.On two occasions the subjects received either placebo or omeprazole60 mg/day 2 days before and during the day test. RESULTS.: Serum gastrin levels were measured as an indicator of achlorhydriaand were 13.7 ± 1 pg/ml after placebo and 30.4 ±4.7 after omeprazole (P <0.003). Postprandial plasma phosphateprofiles were not significantly different between the two studies(+ 36 ± 8% after placebo and + 24 ± 8% after omeprazole,NS), while plasma calcium increased by + 6.1 ± 1% afterplacebo and decreased by – 4.2 ± 0.7% after omeprazole(P < 0.01). The 24-h urinary phosphate excretion was 1068± 85 mg after placebo and 773 ± 55 after omeprazole(P < 0.002), while the 24-h urinary calcium excretion was360 ± 21 after placebo and 238 ± 15 after omeprazole(P < 0.0001). A negative relationship was observed betweenabsolute changes in plasma gastrin and those in urinary calcium(P < 0.009) and phosphate (P < 0.05). CONCLUSIONS.: The inhibition of gastric acid secretion by omeprazole significantlyreduces both urinary phosphate and calcium excretion after anoral load. The behaviour of the postprandial calcium-phosphateplasma profile suggests that gastric acid inhibition is moreeffective in reducing calcium rather than phosphate dietarysalts absorption in normal subjects.     

Serum lipoprotein (a) in renal transplant recipients receiving cyclosporin monotherapy

Coronary heart disease is more common in patients with chronicrenal failure and is a major cause of death after renal transplantation.Elevated serum lipoprotein (a) (Lp(a)) is a known risk factorfor coronary heart disease in the general population. We measured the serum concentration of Lp(a) in 58 renal transplantrecipients (40 male, 18 female) on cyclosporin monotherapy,and in 58 age- and sex-matched controls. Serum Lp(a) was significantlyelevated in the transplant patients with a median of 27.5 (range< 0.8–140.3) mg/dl compared to 7.6 (range <0.8–87.4)mg/dl in controls (P<0.001). Total serum cholesterol, low-densitylipoprotein cholesterol, and total triglyceride concentrationswere also significantly raised (P<0.001) in the transplantrecipients. The increased serum Lp(a) may contribute to the increased cardiovascularmorbidity associated with renal transplantation.     

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.     

Acute Responses of Parathyroid Hormone and 1,25 Dihydroxyvitamin D3 to Unilateral Nephrectomy in Healthy Donors

Plasma immunoreactive parathyroid hormone (iPTH), 1,25(OH)₂D3calcium and phosphate and urinary creatinine, calcium and phosphatewere measured before and following unilateral nephrectomy insix kidney donors. Unexpectedly, plasma calcium rose, from 2.27±0.02mmol/l (mean±SEM) to 2.41±0.03 mmol/l on day 7and to 2.37±0.02 mmol/l on day 30 (P<0.02). A parallelrise in iPTH occurred, from 0.61±0.16 ng/ml initially,to 1.83±0.54 ng/ml on day 7 (P<0.05) and to 1.18±0.18on day 30 (P<0.01). The ratio of maximal tubular reabsorptionof phosphate to GFR (TmP/GFR) fell by day 2 (P<0.001), remainingreduced on day 30 (P<0.05). The significance of elevated iPTH in renal insufficiency wasfurther assessed by determining the time course of the disappearanceof iPTH after parathyroidectomy in three haemodialysis subjects.Fifty per cent baseline iPTH level occurred after an averageof 104.7 min, suggesting that the assay did not predominantlyrecognize C-terminal PTH fragments. By day 2, plasma 1,25(OH)₂D3had fallen from 34.3±4.5 pg/ml to 22.8±3.8 pg/ml(P<0.001), but by day 4 had regained its pre-nephrectomyvalue. Our results suggest that hypocalcaemia may not be thesole stimulus to parathyroid hormone secretion. It is speculatedthat reduction in circulating 1,25(OH)₂D3 may be involved.     

Improvement of Anaemia With Desferrioxamine in Haemodialysis Patients

We have prospectively investigated the effect of desferrioxamine(DFO)administration (2 g i.v. after every haemodialysis session for6 months) on the normocytic and normochromic anaemia of sevenhaemodialysis patients. None had either clinical or analyticaldata characteristic of chronic aluminium intoxication. At theend of DFO therapy, the haematocrit had increased from 20.5±2.7%to 30.4±7.7% (P< 0.005), and the transfusional requirementsdecreased from 3.5±2.2 units (range 1–8 units)in the 6 months prior to DFO, to 0.7±0.9 units (range0–2 units) during DFO administration (P<0.01). No transfusionwas required during the second half of the DFO therapy period.Serum ferritin decreased from 1059±532 nmol/l (2649±1331ng/ml) to 507±403 nmol/l (1268±1008 ng/ml) (P<0.025).Two months after DFO withdrawal the haematocrit value fell significantlyto 22.2±1.6% (P<0.01). DFO therapy was restarted inone patient at a lower dose (1 g i.v. after every haemodialysissession) and an increase of haematocrit from 23.8% to 40.2%was again observed after 3 months of treatment. The toleranceto DFO was excellent. We conclude that DFO therapy should beconsidered in haemodialysis patients with severe anaemia andincreased blood transfusion requirements.     

Symptomatic antiproteinuric treatment decreases serum lipoprotein (a) concentration in patients with glomerular proteinuria

Elevated serum levels of the atherogenic and thrombogenic lipoprotein(a) (Lp(a)) have been recognized as a feature of the nephroticsyndrome associated hyperlipidaemia. To examine a possible relationshipbetween serum Lp(a) concentration and proteinuria, serum albumin,or blood pressure, we studied nine patients with nephrotic-rangeproteinuria both at baseline and after various forms of antihypertensiveand antiproteinuric treatment. In fixed order, patients receivedconventional antihypertensive treatment (either -methyldopaor clonidine), subsequently ACE-inhibition therapy (lisinopril),ACE inhibition combined with an NSAID (indomethacin), and finallyNSAID plus conventional antihypertensive therapy. Measurementswere performed at the end of each 2-month study period. When compared to controls (n = 29), proteinuric patients beforetreatment showed increased levels of total cholesterol, very-lowand low-density lipoprotein (VLDL + LDL) cholesterol, triglyceridesand apolipo-protein B (apoB), while high-density lipoprotein(HDL) HDL cholesterol was lower. Lp(a) was significantly higherin patients (107 (95% CI: 55–208) mg/l) as compared tocontrols (25 (13–49) mg/l, P<0.01). Conventional antihypertensivetreatment did not reduce proteinuria, while Lp(a) remained unaffected.ACE-inhibitor treatment lowered proteinuria, raised serum albumin,while La(a) tended to fall (– 11 ±8%). Additionof an NSAID induced a further fall in proteinuria and a risein serum albumin. Lp(a) now fell by 40±5% from baselinevalues (P<0.01). Both serum total, HDL and VLDL + LDL cholesterolfell significantly. Finally, during subsequent single therapywith NSAID most parameters, including proteinuria and Lp(a),returned towards values obtained during single therapy withACE inhibition. Multiple regression analysis showed a strongrelation of Lp(a) with the amount of proteinuria (P = 0.001),while serum albu-min did not independently contribute to Lp(a)levels (P = 0.2). In conclusion, effective symptomatic antiproteinuric treatmentdecreases serum Lp(a) levels in patients with glomerular proteinuria.Our data suggests that renal protein leakage plays a more importantrole in the metabolic regulation of this lipoprotein than serumalbumin level, and that antiproteinuric treatment may be ofbenefit in reducing the increased risk of thrombosis and atherosclerosisobserved in this patient category.     

Renal effects of maintenance low-dose cyclosporin A treatment in psoriasis

The renal effects of low-dose cyclosporin A (CsA) treatmentin severe psoriasis was investigated in 10 patients treatedwith a mean CsA dose of 3.23 (range 1.94–4.10) mg/kg/dayfor 12 months. The psoriasis area and severity index was reducedby 63–76%. Ambulatory GFR (iothalamate-¹²⁵I) ERPF (hippuran-¹³¹),RVR and MAP were examined at 3-months intervals. A control renalbiopsy was performed shortly before treatment start and a secondbiopsy was taken after 12 months of therapy. GFR was slightlybut significantly reduced after 6 and 9 months; after 12 monthsthe decrease was not significant (121.0±7.6 versus 115.2±7.8ml/min/l.73M P>0.10). After 12 months serum creatinine increasedfrom 82±4 to 94±7 µmol/litre (P<0.05while an insignificant increase of ERPF was seen and FF decreasedfrom 0.29±0.01 to 0.26±0.01 (P<0.05). MAP remainedunchanged. GFR and serum creatinine correlated significantlywithin each 3-month interval. A slight de novo interstitialfibrosis was seen in the second biopsy in 4 of 10 patients receivinga mean CsA dose of 3.2–4.1 mg/kg/day. In three of thesepatients a concomitant rise in serum creatinine was seen. In conclusion, low-dose CsA was associated with reversible fallin GFR and potentially progressive structural changes not alwaysaccompanied by corresponding functional alterations. One shouldconsider reducing the daily dose of CsA to 3.0 mg/kg body- weightor less in CsA therapy up to 1 year.     

The Use of Calcium Carbonate to Treat the Hyperphosphataemia of Chronic Renal Failure

This study evaluates the use of calcium carbonate in chronicrenal failure. Forty-eight patients (25 male, 23 female, meanage 54.3 years, six pre-dialysis, 12 CAPD, 30 haemodialysis)on phosphate restriction and requiring aluminium hydroxide (mean2.4±0.8 g/ day) to control serum phosphate, were convertedto an equivalent dose of calcium carbonate (2.5±0.6 g/day).None received vitamin D analogues. Three months post-conversionthere was a significant decrease in mean (±SEM) serumphosphate (1.86±0.08 versus 1.66±0.05 mmol/l,P<0.01) and serum aluminium (28.3±5.4 versus 13.2±3.0µg/l,P<0.0001); calcium/phosphate product was unchanged. Post-conversionthere was an increase in serum bicarbonate, (20.6±0.5versus 22.1±0.6 mmol/l, P<0.01) and serum calcium(2.32±0.02 versus 2.45±0.03 mmol/l, P<0.0001).No change in serum creatinine, alkaline phosphatase or parathormoneoccurred. No adverse effects were reported but nine (18%) patientsbecame hypercalcaemic (2.7 to 2.93 mmol/l), eight of whom respondedto dose reduction. Hypercalcaemia did not correlate with pre-conversionserum calcium, parathyroid hormone, alkaline phosphatase oraluminium. Calcium carbonate is an effective alternative toaluminium-based phosphate binders. It produces a beneficialincrease in serum calcium and bicarbonate and a significantdecrease in serum aluminium. Hypercalcaemia is unpredictablebut is easily reversible in the majority of patients.     

Dietary Fish Oil Supplements Preserve Renal Function in Renal Transplant Recipients with Chronic Vascular Rejection

The effect of dietary fish oil supplements on renal failureand lipid abnormalities was studied in 14 adult renal transplantrecipients with chronic vascular rejection. The rate of declineof renal function (assessed by studying the slope of reciprocalplasma creatinine plots) slowed significantly during a 6-monthperiod on fish oil supplements compared with the preceding 6-monthcontrol period (slope 1/cr during supplementation –3.6x 10^–5 µmol/l per month compared with –13.5x 10^–5 before, the difference in slope being –9.8x 10^–5, 95% confidence interval (CI) –16.2 x 10^–5,–3.5 x 10^–5, P<0.05). Total plasma triglycerideconcentrations decreased during supplementation (mean change–1.15 mmol/l, 95% CI –1.84, –0.47, P<0.003),but there was no change in total plasma cholesterol concentrationor urinary protein excretion. Platelet function was studiedin nine patients. Platelet aggregation induced by adrenalineand collagen was reduced by fish oils (median change in percent aggregation), adrenaline 2 µmol/ –36% (95%CI –68%, –8%, P<0.05), collagen 1 mg/l, –13%(95% CI –44%, –2%, P<0.05). Platelet thromboxaneA₂ release in response to these agents was also significantlyreduced. These results demonstrate that fish oils preserve residualfunction in renal graft failure due to chronic vascular rejection.     

Efficacy, safety and tolerability of atorvastatin in dyslipidemic subjects with advanced (non-nephrotic) and endstage chronic renal failure

Background Patients with dyslipidemia and advanced renal failure are at markedly increased risk of cardiovascular morbidity and mortality. We evaluated the efficacy, safety, and tolerability of atorvastatin in non-nephrotic, dyslipidemic patients with chronic renal failure (CRF) or endstage renal failure (ESRF) receiving dialysis. Methods Following a 6-week baseline period, adult patients meeting Australian Heart Foundation treatment guidelines received atorvastatin for 16 weeks: 19 with CRF (predialysis), 17 on hemodialysis (HD), and 13 on continuous ambulatory peritoneal dialysis (CAPD). Dose (10–40 mg daily) was titrated to achieve lipid-lowering targets. Efficacy was determined by monitoring lipids (principally triglycerides and low-density lipoprotein [LDL] cholesterol); safety and tolerance by monitoring clinical and laboratory parameters. Results Atorvastatin was effective in reducing LDL cholesterol from baseline at each of weeks 4, 8, 12, and 16 in all study groups, with reductions of more than 40% at week 16. Sixty-two percent of PD, 73% of HD, and 100% of CRF patients were at or below target (<2.6 mmol/l) for LDL cholesterol at week 16. Significant reductions in triglycerides (approximately 27%) were seen in the CRF and combined HD/CAPD groups at all time points. Depending on the group, 65%–83% of patients were at or below target (<2.0 mmol/l) for triglycerides at week 16. The majority of patients received the 10-mg dose. Atorvastatin also reduced total cholesterol and apolipoprotein B levels in all groups and very-low-density lipoprotein (VLDL) cholesterol in the CRF group. Significant increases in LDL particle size were found in the HD and combined HD/CAPD groups. Minor, particularly gastrointestinal, symptoms were common. Three patients reported musculoskeletal symptoms, but creatine kinase was raised in only one. Conclusion Atorvastatin is an effective lipid-lowering agent for dyslipidemic subjects with advanced and endstage renal failure, and was reasonably well tolerated.     

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.     

Plasma lipoproteins and renal apolipoproteins in rats with chronic adriamycin nephrosis

The relation between plasma lipoprotein composition and renalapolipoprotein deposition was studied in nephrotic rats in whichstable renal function had been monitored for 7 months aftera single low dose of adriamycin (ADR, 3 mg/kg). Proteinuriawas observed 3 weeks after ADR and increased progressively upto about 0.5 g/day (versus 0.07 g/day in controls; P< 0.001),while the creatinine clearance remained stable at about 80%of control values. Hypercholesterolaemia was observed 6 weeksafter ADR, and increased progressively up to 7.0±1.0mmol/l (versus 2.3±0.1 mmol/l in controls; P<0.001).Cholesterol was primarily located in LDL2 and HDL2 lipoproteins.Plasma apolipoprotein (apo) A-I increased by more than 400%in the nephrotic rats (/><0.001). Apo B and apo E increasedby about 60% (P<0.01), whereas apo A-IV remained unchanged.Focal sclerotic lesions in glomeruli had an incidence of 50±10%in ADR rats versus 2±1% in controls (P<0.001). Immunohistochemistryrevealed apo A-I and apo A-IV in the visceral epithelium. ApoE immunoreactivity and lipid deposits were observed in focalglomerular sclerotic lesions of ADR rats. Neither apolipoproteinsnor lipids were detected in glomeruli of controls. Proximaltubular localization of apolipoproteins was extensive for apoA-I, apo A-IV and apo E, but no differences were observed intubular deposition of apolipoproteins between ADR and controlrats. Chronic proteinuria induced by a single low dose of ADRin rats is a promising model to study the alleged pathogeneticrole of hyperlipidaemia in relation to mesangial apolipoproteinE and lipid deposition in the deterioration of renal functionand morphology in the nephrotic syndrome.     

Elevated plasminogen activator inhibitor levels in cyclosporin-treated renal allograft recipients

Atherosclerosis and thrombosis, two major causes of morbidityand mortality in renal transplant recipients, share the sameclinical risk factors including decreased fibrinolysis and lipiddisturbances. In a crosssectional study we have determined parametersof fibrinolysis in control subjects (n=23) and stable renalallograft recipients without cyclosporin CsA (n=10) and withCsA (n=87) in their immunosuppressive treatment. In CsA-treatedpatients, tissue-type plasminogen activator was moderately increasedcompared to patients without CsA (8.4±3.3 vs 5.5±2.8ng/ml). The plasminogen activator inhibitor (PAI) activity inplasma was clearly increased in CsA-treated patients: 14.5±8.8vs 7.2±3.2 in normal controls and 8.5±2.4 AU/mlin patients without CsA. Total cholesterol and LDL cholesterollevels were higher in CsA-treated patients (256±62 and169±60 mg/dl) than in patients without CsA (209±45and 136±44 mg/dl). The two groups did not differ in HDLcholesterol, triglycerides, and lipoprotein(a). Hypercholesterolaemia,obesity, and steroid-induced diabetes could be identified asrisk factors for elevated plasma PAI activity in CsA-treatedpatients. Hypofibrinolysis induced by elevated PAI levels andincreased LDL cholesterol may contribute to the increased thrombogenicityand accelerated atherosclerosis observed in cyclosporin-treatedpatients.