Insulinogenic index in non-diabetics during haemodialysis.

BACKGROUND: The aim of this study was to analyse whether the insulin to glucose relationship following an intravenous glucose load in non-diabetic patients delivered during haemodialysis was affected by extracorporeal clearance and whether this relationship could be determined by an abridged sampling protocol. METHODS: Studies were done during routine haemodialysis following the infusion of 0.5 g glucose per kilogram body mass. Extracorporeal effects were measured by online clearance (K(OCM)) and insulin clearance (K(I)). The insulin to glucose relationship was examined for a period of 1 h following the infusion of glucose. The integral response measured as the insulinogenic index (I(G)) was compared to the relationship between insulin and glucose concentrations measured for the whole period (k(IG)) as well as from only two samples taken at baseline and after 10 min (k(10)). RESULTS: Eight non-diabetic haemodialysis patients (three females) with a dry body mass of 76.9 ± 18.2 kg completed the study. I(G) was 5.4 ± 4.4 U/mol and not different from normal reference values. A linear relationship providing characteristic slopes k(IG) was observed between arterial insulin and glucose levels. k(IG) was 6.1 ± 5.0 U/mol and not different from k(10) = 5.9 ± 4.8 U/mol measured after 10 min of glucose infusion and ongoing dialysis. I(G), k(IG) and k(10) were highly correlated (P < 0.0001), and k(10) showed substantial concordance (ρ(c) = 0.99) with I(G). Moreover, I(G), k(IG) and k(10) were independent of K(OCM) or K(I). CONCLUSIONS: The insulin to glucose relationship is measurable within 10 min of glucose administration and unaffected by extracorporeal clearance. This could be helpful to characterize the insulin response to a glucose stimulus during haemodialysis.

Efficacy and safety of anticoagulation with heparin versus heparin plus epoprostenol in patients undergoing extracorporeal liver support with Prometheus.

Anticoagulation for extracorporeal liver support is delicate due to underlying coagulation disorders in patients with liver failure and to the associated elevated bleeding risk. To date, there has been no detailed report on anticoagulation issues in patients treated with Prometheus, a device based on the principle of fractionated plasma separation and adsorption. We studied 17 patients from two centers treated with Prometheus, comparing standard anticoagulation with heparin (15 treatments) and a combination of heparin and the synthetic prostacyclin epoprostenol (22 treatments). Standard coagulation tests, proteins C and S, and thrombin-antithrombin (TAT) complex were determined, and adverse events were recorded. All but two treatments could be completed as scheduled, although filter exchange due to filter clotting was required in 24% of the treatments. Three out of 17 patients developed severe bleeding complications within 24 h of treatment. There were no overt thrombotic events. Addition of epoprostenol neither reduced coagulation-related adverse events nor improved standard coagulation parameters. Protein C, but not protein S, showed a significant reduction (23 +/- 18%) after Prometheus treatments, but levels rebounded to baseline within 18 h. TAT levels--a measure for activation of coagulation--were only altered by Prometheus in patients where TAT was already elevated before treatment. In conclusion, anticoagulation of Prometheus with heparin is feasible but still associated with a relatively high frequency of filter clotting and a considerable risk of severe bleeding in this high-risk patient population. As addition of epoprostenol did not prove beneficial, other strategies, such as regional anticoagulation with citrate, should be further evaluated.

Antioxidant status of patients on peritoneal dialysis: associations with inflammation and glycoxidative stress.

BACKGROUND: Patients on peritoneal dialysis (PD) frequently exhibit oxidant-antioxidant imbalance, advanced glycation end-product overload, and subclinical inflammation but the interrelations between these pathophysiological changes have not been fully elucidated. SUBJECTS AND METHODS: To study possible associations, a cross-sectional study of antioxidant status, glycoxidative stress, and inflammation, using HPLC and ELISA methods, was undertaken in 37 PD patients and age- and sex-matched healthy controls. RESULTS: Plasma ascorbate concentrations were low in patients not taking at least low-dose vitamin C supplements. In patients taking vitamin C supplements, there was a positive relation between ascorbate and pentosidine concentrations. Vitamin E and carotenoid concentrations were comparable between patients and controls, while lycopene and lutein/zeaxanthin concentrations were lower. Interleukin-6, C-reactive protein (CRP), and pentosidine concentrations were elevated in PD patients. beta-Cryptoxanthin, lycopene, and lutein/zeaxanthin concentrations were inversely related to interleukin-6 concentrations. beta-Cryptoxanthin concentrations were also inversely related to CRP concentrations. Pentosidine showed a low dialysate-to-plasma ratio, indicating low peritoneal clearance. Pentosidine concentrations increased with duration of PD therapy, while alpha- and beta-carotene concentrations decreased. Malondialdehyde concentrations were elevated compared to controls but remained within the normal range. Retinol concentrations decreased with PD therapy and were inversely related to interleukin-6 and CRP concentrations. CONCLUSIONS: Low-dose vitamin C supplements and a carotenoid-rich diet should be recommended for PD patients to maintain normal antioxidant status and efficiently counteract the chronic inflammatory response, rather than high doses of vitamin C, which could play a role as a precursor of pentosidine.

Drug reactions - new observations.

This Macro-Micro-Dermatology-contribution with the theme innovative drugs and drug reactions illustrates two new observations of practical interest: 1. Follicular eruption after Everolimus and 2. Atrophy of sebaceous glands after Sirolimus.

Decrease in thoracic vertebral bone attenuation with calcium-based phosphate binders in hemodialysis.

UNLABELLED: We performed a post hoc analysis of a 52-week randomized trial conducted in adult hemodialysis patients that compared the effects of calcium-based phosphate binders and sevelamer, a nonabsorbable polymer, on parameters of mineral metabolism and vascular calcification by electron beam tomography. In this analysis, we evaluated the relative effects of calcium and sevelamer on thoracic vertebral attenuation by CT and markers of bone turnover. Subjects randomized to calcium salts experienced a significant reduction in trabecular bone attenuation and a trend toward reduction in cortical bone attenuation, in association with higher concentrations of serum calcium, lower concentrations of PTH, and reduced total and bone-specific alkaline phosphatase. INTRODUCTION: In patients with chronic kidney disease, hyperphosphatemia is associated with osteodystrophy, vascular and soft tissue calcification, and mortality. Calcium-based phosphate binders are commonly prescribed to reduce intestinal phosphate absorption and to attenuate secondary hyperparathyroidism. Clinicians and investigators have presumed that, in hemodialysis patients, calcium exerts beneficial effects on bone. MATERIALS AND METHODS: We performed a post hoc analysis of a 52-week randomized trial conducted in adult hemodialysis patients that compared the effects of calcium-based phosphate binders and sevelamer, a nonabsorbable polymer, on parameters of mineral metabolism and vascular calcification by electron beam tomography. In this analysis, we evaluated the relative effects of calcium and sevelamer on thoracic vertebral attenuation by CT and markers of bone turnover. RESULTS AND CONCLUSIONS: The average serum phosphorus and calcium x phosphorus products were similar for both groups, although the average serum calcium concentration was significantly higher in the calcium-treated group. Compared with sevelamer-treated subjects, calcium-treated subjects showed a decrease in thoracic vertebral trabecular bone attenuation (p = 0.01) and a trend toward decreased cortical bone attenuation. More than 30% of calcium-treated subjects experienced a 10% or more decrease in trabecular and cortical bone attenuation. On study, sevelamer-treated subjects had higher concentrations of total and bone-specific alkaline phosphatase, osteocalcin, and PTH (p < 0.001). When used to correct hyperphosphatemia, calcium salts lead to a reduction in thoracic trabecular and cortical bone attenuation. Calcium salts may paradoxically decrease BMD in hemodialysis patients.

Effect of hemodialysis on the antioxidative properties of serum.

In patients with chronic renal failure undergoing regular hemodialysis (HD), oxidative stress is involved in the development of dialysis-related pathologies. The aim of the study was to measure the effect of HD treatment on the general antioxidative status of serum with special consideration of the specific oxidizability of lipids and proteins. Indicators for the oxidative/antioxidative status of plasma were monitored at the beginning and at the end of a dialysis session on the arterial and venous side of the dialyzer. A decrease in the antioxidant status was accompanied by an increased oxidizability of proteins as well as lipids during HD treatment. During the first passage of the dialyzer, the lag time of lipid oxidation decreased from 114.0+/-19.8 to 81.5+/-18.9 min, the lag time of protein oxidation decreased from 105.0+/-24.6 to 72.9+/-21.3 min and the total antioxidative status decreased from 518+/-24 to 252+/-124 microM trolox equivalents. The carbonyl content of serum proteins was high in patients with end stage renal disease (ESRD) (3.9+/-1.1 vs. 0.9+/-0.1 nmol/mg in controls) but did not change significantly during dialysis procedure. Our data demonstrate that the susceptibility of serum lipids and proteins to oxidative modification is severely increased by HD treatment.

[Treatment of renal anemia with darbepoetin alfa: results of an Austrian multicenter study]. / Behandlung der renalen Anämie mit Darbepoetin alfa--Ergebnisse einer österreichischen Multicenter-Studie.

Darbepoetin alfa is a unique erythropoetic protein whose half-life is 3 times longer than that of recombinant human erythropoetin (rHuEPO). It corrects and maintains haemoglobin (Hb) concentrations at increased dosing intervals as compared to rHuEPO. The aim of this study was to evaluate the efficacy and safety of darbepoetin alfa administered as fixed unit doses. Haemodialysis patients (n = 250) maintained on stable rHuEPO treatment 2-3 times weekly (n = 200) were switched to darbepoetin alfa once weekly (QW). Treatment for patients on rHuEPO QW (n = 50) was changed to darbepoetin alfa every other week (Q2W). The route of administration (i.v. or s.c.) was kept unchanged. The dose of darbepoetin alfa was titrated to maintain Hb levels at 10-13 g/dL between baseline and the evaluation period (weeks 21-24; primary endpoint). There was no clinically relevant change in mean Hb levels between baseline (11.69 g/dL) and evaluation (-0.28 g/dL (95% CI: -0.43; -0.13)). Mean weekly dose requirements of darbepoetin alfa decreased by 13.3% from 36.7 micrograms (95% CI: 33.9; 39.7) to 31.8 micrograms (95% CI: 28.7; 35.2). This decrease was more pronounced in patients receiving darbepoetin alfa i.v. (-18.4%) as compared to those receiving it s.c. (-6.4%). Darbepoetin alfa was well tolerated. Overall safety data were consistent with those observed in other studies. These data confirm that unit dosing with darbepoetin alfa at increased dosing intervals and reduced dose effectively and safely maintains Hb levels in haemodialysis patients.

Antioxidant treatment of therapy-resistant idiopathic membranous nephropathy with probucol: a pilot study.

BACKGROUND: Proteinuria in Heymann's nephritis, an experimental rat model disease corresponding to membranous nephropathy, has been shown to be due to lipid peroxidation. Since the pathophysiology might be similar to idiopathic membranous nephropathy in humans, we performed a prospective multicenter trial to investigate the efficacy of the lipid peroxidation scavenger, probucol. METHODS: Fifteen patients with biopsy-proven idiopathic membranous nephropathy resistant to conventional immunosuppressive therapy (n = 7) and/or ACEI treatment (n = 12) were recruited. Probucol (1 g/d orally) was administered for three months, followed by a washout period of four weeks, whereon lovastatin (10-20 mg/d orally) was administered for additional three months. RESULTS: A significant reduction in proteinuria was seen during the probucol treatment (median (range): 6.4 (3.8-9.1) g/d vs. 4.7 (1.3-16) g/d; P < 0.05), with partial remission achieved in four patients. Three of these patients had previously been resistant to immunosuppressive therapy. Median protein excretion increased to pretreatment values during the washout period (6.2 (1.9-15) g/d; P < 0.05) and was not significantly different after the intake of lovastatin (4.9 (1.8-19) g/d; P = NS). None of the patients achieved partial remission during lovastatin therapy (P < 0.05 vs. probucol). CONCLUSION: The present study led us to conclude that proteinuria can be reduced by probucol in some patients with idiopathic membranous nephropathy. A randomized multicenter study to further elucidate the influence of lipid peroxidation scavengers on membranous nephropathy is warranted.

Intracorporeal glucose disposal during hemodialysis after a standardized glucose load.

The aim of this study was to quantify intracorporeal clearance and disposal of glucose after the administration of a standardized glucose load during regular hemodialysis done in stable and non-diabetic patients and to account for effects of extracorporeal clearance. A standardized load of glucose was administered approximately 30 min after starting hemodialysis with a constant dialysate glucose of 5.0 +/- 0.2 mmol/L. Glucose in the arterial line blood and in dialysate outflow was measured at baseline and in short intervals for a period of 1 h after the infusion. Tests were repeated within 1 week. Nine patients completed the study. Extracorporeal blood and dialysate flows were 304 +/- 34 and 500 mL/min, respectively. The intracorporeal clearance of glucose was 327 +/- 137 mL/min and 69.1 +/- 9.4% of total glucose clearance. Mass balance assessed from dialysate samples showed that 60.1 +/- 10.5% of glucose injected was disposed intracorporeally. The fraction of intracorporeal clearance and the fraction of intracorporeal glucose disposal were highly correlated (r = 0.94, p < 0.0001). The fraction of glucose disposed in hemodialysis patients can be determined from the amount of glucose injected and from the amount of glucose removed extracorporeally during hemodialysis without blood sampling. This measure could be of interest in surveillance of glucose control in hemodialysis patients.

Renal transplant patients at high risk of acute rejection benefit from adequate exposure to mycophenolic acid.

BACKGROUND: To better define subpopulations in which achieving adequate mycophenolic acid (MPA) concentrations quickly would be important, a post hoc exploratory analysis on the fixed-dose concentration-controlled database was performed, comparing high- versus low-risk renal transplant patients. METHODS: Renal transplant patients were treated with mycophenolate mofetil, corticosteroids, and cyclosporine A or tacrolimus. Patients were defined as "high risk" if they had one or more of the following characteristics: delayed graft function, second or third transplantation, panel reactive antibodies >15%, four or more human leukocyte antigen mismatches, or were of black race. RESULTS: A total of 549 patients (61%) were classified as high risk, of whom 284 were on cyclosporine A treatment and 265 on tacrolimus. In high-risk patients, the difference in rejection incidence was 14.3% in the MPA-area under the concentration (AUC) less than 30 mg hr/L vs. 7.8% in the MPA-AUC more than or equal to 30 mg hr/L groups (P=0.025) during the first month after transplantation; whereas, in low-risk patients, there were similar rejection rates (5.7% vs. 4.5%). In the subgroup of high-risk tacrolimus-treated patients, the difference in acute rejection incidence in the first month between patients with MPA-AUC0-12 less than or more than or equal to 30 mg hr/L was most pronounced: 16 of 67 patients (23.9%) vs. 18 of 173 patients (10.4%); P=0.012. CONCLUSIONS: The incidence of acute rejection is higher in high-risk patients if MPA-AUC0-12 is below 30 mg hr/L. In contrast, a difference in acute rejection incidence in low-risk patients with MPA-AUC0-12 less than or more than or equal to 30 mg hr/L was not observed. This supports the use of a higher mycophenolate mofetil starting dose in selected patient populations early after transplantation.

Anderson-Fabry disease: a case-finding study among male kidney transplant recipients in Austria.

The diagnosis of Anderson-Fabry disease is often delayed or even missed. As severe renal manifestations are a hallmark of alfa-galactosidase A (AGAL) deficiency, we tested the hypothesis that Anderson-Fabry disease is under-recognized among male kidney transplant recipients. This nation-wide study in Austria enrolled 1306 patients (ca 65% of all kidney transplanted males) from 30 kidney centers. AGAL activity was determined from filter paper dried blood spots by a fluorescence assay. A positive screening test was defined by an AGAL activity below 1.5 nmol/h/ml. In patients with a positive blood spot-screening test, AGAL activity was re-examined in peripheral blood leukocytes. Genetic testing for mutations in the GLA gene was performed by sequencing to confirm the diagnosis of Anderson-Fabry disease. Two previously not recognized cases with Anderson-Fabry disease were identified. Our study is the first showing that a diagnosis of Anderson-Fabry disease can be missed even in patients who undergo kidney transplantation. Case-finding strategies may be considered a useful tool for diagnosis of this rare disease that may be somewhat more prevalent among kidney transplant recipients compared with dialysis populations.

Bone markers predict cardiovascular events in chronic kidney disease.

Recent studies have indicated a link between bone metabolism and cardiovascular events in patients with chronic kidney disease (CKD). CKD is a major health problem worldwide. This study evaluates the role of noninvasive markers of bone metabolism in predicting cardiovascular morbidity (coronary artery disease, peripheral vascular disease, stroke) and mortality in patients with mild to severe forms of CKD. In a prospective cohort study, 627 patients with CKD were screened. To focus on bone metabolism, traditional risk factors for cardiovascular events were excluded, and 135 patients with CKD stages 1-5 were followed for 4 yr. Glomerular filtration rate was calculated by the Modification of Diet in Renal Disease formula. PTH (measured by four different assays), vitamin D 25 and 1,25, bone-specific alkaline phosphatase (BSALP), TRACP-5b, osteocalcin, serum collagen cross-link molecules, RANKL, and osteoprotegerin were determined. Predictors of cardiovascular events were evaluated by multivariable logistic regression, Kaplan-Meier survival, and Cox regression analysis. There were a total of 45 cardiovascular events (33%). Event rates were 5.6%, 29.1%, 45.2%, and 45.0% in CKD stages 1-2, 3, 4, and 5, respectively. In logistic regression, cardiovascular events were predicted only by (1) CKD stage (independent of age or sex; p < 0.001); (2) BSALP (p = 0.03); and (3) TRACP-5b (p = 0.04). Markers of bone formation (BSALP) and resorption (TRACP-5b) can serve as predictors of cardiovascular morbidity and mortality in CKD.

Removal of bile acids by two different extracorporeal liver support systems in acute-on-chronic liver failure.

Acute-on-chronic liver failure (ACLF) is accompanied by marked intrahepatic cholestasis leading to accumulation of cytotoxic bile acids. Extracorporeal liver support systems efficiently remove bile acids, but their effect on bile acid composition in ACLF is unknown. The aim of the present study was to compare elimination of individual plasma bile acids by albumin dialysis (Molecular Adsorbents Recirculating System, MARS) and fractionated plasma separation (Prometheus). Eight consecutive patients with ACLF underwent alternating 6-hour sessions with MARS or Prometheus in a randomized, cross-over design. Serum samples were obtained before, during, and after each treatment, and individual bile acids including cholic acid and chenodeoxycholic acid (CDCA) were measured by gas chromatography. MARS and Prometheus removed total bile acids to a similar extent (reduction ratio, 45% and 46%, respectively). Both devices cleared cholic acid more efficiently than did CDCA. The molar fraction of CDCA (fCDCA) was elevated at baseline and correlated with the degree of liver dysfunction. Prometheus but not MARS treatments further increased fCDCA. Although both devices eliminate total bile acids to a similar extent, clearance of individual bile acids is different, leading to a slight change of the bile acid profile toward hydrophobic bile acids during Prometheus treatments.

Device and technique for extracorporeal blood volume sequestration during hemodialysis.

We developed a technique for a controlled and reversible volume perturbation of the cardiovascular system during hemodialysis. The capacitance of the extracorporeal circulation was modified by an expansion bag, using separate filling and draining lines connected to postpump and prepump sections of the arterial line segment, respectively. The connection to this bag was manually operated by three-way valves. The volume sequestered into the blood bag was continuously measured by a weighing scale. Filling and draining of the expansion bag was measured in eight patients in two subsequent routine dialysis treatments. Four volume shifts were done in each treatment. Filling and draining rates and times depended on extracorporeal blood flow as well as arterial and venous line pressures. Bag inflow and outflow volumes were 215.8 +/- 28.5 ml/min and 221.6 +/- 37.0 ml/min, respectively. The total volume transiently sequestered in the bag was 479.8 +/- 61.3 ml. The duration of the whole test was 4.5 +/- 0.8 minutes. During filling, residual dialyzer blood flow was transiently reduced to 58.5 +/- 21.6 ml/min and the filtration fraction reached 30 +/- 13%. There were no adverse events such as clotting in the blood bag or in the dialyzer. The method provides rapid, reversible, and safe volume shifts between the patient and the extracorporeal circulation with the potential to elicit a hemodynamic response for characterizing the patient during each dialysis treatment.

Bilirubin kinetic modeling for quantification of extracorporeal liver support.

BACKGROUND/AIM: To provide a measure of treatment dose for extracorporeal liver support (ELS). METHODS: The kinetics of conjugated bilirubin were described by a two-compartment model (Vc, Vp) with central elimination (K) and constant generation rate (G). The transfer of solute between compartments was modeled by intercompartmental clearance (Kpc). The central compartment (Vc) was assumed as a constant fraction of total volume (Vc = 0.3*Vt). RESULTS: Eight patients were studied during 35 treatments lasting 6 h each. The average K, Vt, Kpc, G, and mass of conjugated bilirubin removed were 18.6 +/- 3.9 ml/min, 9.1 +/- 3.8 liters, 103 +/- 108 ml/min, 0.33 +/- 0.15 mg/min, and 641 +/- 275 mg, respectively. The reduction ratio (48 +/- 10%) measured as the change in post- to pre-treatment concentrations underestimated the modeled fraction of bilirubin mass removed (54 +/- 13%) essentially because of significant conjugated bilirubin appearance during treatments. CONCLUSIONS: Kinetic analysis provides an improved measure of treatment dose as generation, distribution, and elimination of conjugated bilirubin are jointly considered.

In vivo quantification of liver dialysis: comparison of albumin dialysis and fractionated plasma separation.

BACKGROUND/AIMS: Artificial liver support represents a potentially useful option for the treatment of severe liver failure. A sufficient 'dose' might be crucial for such treatments to provide a survival benefit. The aim of this study was to compare in vivo efficiency and resulting delivered treatment dose of two commercially available devices that use different therapeutic principles: albumin dialysis (AD, MARS) and fractionated plasma separation (FPS, Prometheus). METHODS: Eight patients with acute-on-chronic liver failure were treated alternately with AD and FPS. Thirty-two treatments at identical blood and dialysate flow rates were evaluated. Clearance and reduction ratio (a measure of delivered treatment dose) were compared for bilirubin subfractions, ammonia and urea. RESULTS: FPS achieved significantly higher clearance for all measured protein-bound and water-soluble markers. This resulted in significantly higher reduction ratios for FPS compared to AD. Unconjugated bilirubin, a marker for strongly albumin-bound toxins, was influenced only by FPS. CONCLUSIONS: FPS provided a higher delivered treatment dose than a matching treatment with AD. Reduction ratios of bilirubin and urea should be reported in clinical studies on liver dialysis, since delivered dose is likely to be linked to the clinical effectiveness of extracorporeal liver support therapies.

Two year comparison of sevelamer and calcium carbonate effects on cardiovascular calcification and bone density.

BACKGROUND: Calcium-based phosphate binders may induce tissue calcification, and little is known about their effects on bone density. We compared the effects of a calcium with a non-calcium phosphate binder on both arterial calcification and bone density measured by computed tomography. METHODS: Seventy-two adult haemodialysis patients were randomized to treatment with calcium carbonate (CC) or sevelamer (SEV) for 2 years. Electron beam CT scans were performed at baseline and at 6, 12 and 24 months. Serum phosphorus, calcium, calcium x phosphorus product and intact parathyroid hormone (iPTH) were measured and other routine laboratory tests were also carried out. RESULTS: The average calcium x phosphorus product was similar in the two treatment groups. However, patients receiving CC had significantly lower average iPTH (P<0.01), were more likely to have hypercalcaemic episodes (P = 0.03) and had significantly greater increases in coronary artery (CC median 484, P<0.0001, SEV median 37, P = 0.3118, between-group P = 0.0178) and aortic (CC median 610, P = 0.0003, SEV median 0, P = 0.5966, between-group P = 0.0039) calcification scores. The CC group also had a significant decrease in trabecular bone density (CC median -6%, P = 0.0049, SEV median +3%, P = 0.0296, between-group P = 0.0025). However, there was no significant difference in cortical bone density between the two groups. CONCLUSIONS: This 2 year study shows that calcium carbonate use is continuously associated with progressive arterial calcification in haemodialysis patients. In addition, it suggests that it is also associated with decreased trabecular bone density. However, this latter finding requires confirmation by a study specifically devoted to this issue.

Assessment of renal functional reserve by dynamic renal function testing.

Renal clearances of suitable clearance markers such as inulin and p-aminohippurate, determined before and after protein load, have been used for a long time to determine glomerular filtration rate (GFR), renal blood-flow, renal functional reserve as well as renal vascular resistance. Despite this long history, inconsistent results were achieved in determining renal functional reserve after protein ingestion or aminoacids infusion. Most authors found acute 'blunted increases' in GFR after dietary stresses, whereas others found acute decreases. In hypertensive patients showing hyperfiltration, a contradictory situation was observed; the traditionally observed 'blunted increase' in GFR and increase in the intraglomerular pressure were neither accompanied by a change in albumin excretion nor by an expected dynamic GFR response after administration of angiotensin converting enzyme (ACE)-inhibitors. We are of the opinion that the traditional clinical methods for assessing acutely provoked changes in renal function have been inappropriate and that an approach based on the two-compartment model of pharmacokinetics is more adequate for studying dynamic clearance changes within clinically feasible time horizons. Such test evaluations performed in patients within a washout period, and after long-term treatment with various drugs enable one to assess the efficacy of the therapeutic regimens especially in patients showing apparently normal or increased baseline clearances in hyper filtering kidneys.

Prediction of time-averaged concentration of haemoglobin in haemodialysis patients.

BACKGROUND: Haemoglobin (Hb) concentration is not stable in most haemodialysis patients due to ultrafiltration-induced haemoconcentration. Pre-dialysis Hb concentrations might therefore significantly deviate from the time-averaged concentration (Hb-tac) which is more likely to represent the patients 'true' Hb. This study was performed to quantify these differences in our chronic haemodialysis population and to develop a formula for prediction of Hb-tac. METHODS: In 55 stable patients, serial blood samples were taken over a period of 2 weeks before and immediately after each haemodialysis as well as 30 min post-haemodialysis to account for post-dialytic fluid rebound. Hb-tac was calculated for every patient from the area under the time-dependent Hb curve. We compared the differences between Hb-tac and pre-dialysis Hb (Hb-pre) and various prediction formulae for Hb-tac generated by multiple linear regression analysis which included Hb-pre and post-dialysis Hb (Hb-post) and/or ultrafiltration rate (UFR). RESULTS: Mean Hb-pre after the long dialysis interval was significantly lower than after the short interval (11.47 vs 11.85 g/dl, P < 0.0001), both underestimating mean Hb-tac (11.97 g/dl). More interestingly, Hb-pre after the long interval deviated >0.5 g/dl from Hb-tac in 50% of measurements. After the short interval, 20% still lay outside this tolerance range. The best formula to predict Hb-tac was Hb-pre x 0.5 + Hb-post x 0.38 + 1.28 (6% outside +/- 0.5 g/dl). Hb-pre +(Hb-post - Hb-pre)/3 may be used for quick estimation of Hb-tac. CONCLUSIONS: Hb-tac can be predicted from pre- and post-dialysis blood samples after the short interval, using a simple new formula. Because Hb-tac more reliably reflects a 'true' Hb level of haemodialysis patients, it represents a potentially useful tool for future scientific and clinical work.

High prevalence of Chlamydia pneumoniae infection in cyclosporin A-induced post-transplant gingival overgrowth tissue and evidence for the possibility of persistent infection despite short-term treatment with azithromycin.

BACKGROUND: Cyclosporin A (CsA) induces gingival overgrowth (GO) in up to a quarter of CsA-treated renal transplant recipients. A short-term therapy with azithromycin effectively reduces GO, indicating a possible involvement of microorganisms in the pathogenesis of CsA-induced GO. We aimed to determine if there could be any relationship between infection with Chlamydia pneumoniae and GO pathogenesis. In addition, we determined the long-term persistence rate of C. pneumoniae infection in residual GO tissue when azithromycin treatment failed to eliminate GO. METHODS: Chlamydia pneumoniae IgG and IgM antibody titres were measured by microimmunofluorescence technique in sera of kidney recipients with (n = 11) and without (n = 89) GO. GOs were rated and gingivectomies were performed before treatment with 500 mg of azithromycin for 3 days and at months 6 and 12 post-treatment when C. pneumoniae titres were re-evaluated. Nested polymerase chain reaction was performed to identify C. pneumoniae-specific DNA in GO tissues. Results of C. pneumoniae antibody titres from patients with GO were compared with pair-matched controls without GO. RESULTS: Chlamydia pneumoniae IgM titres were elevated in five of 11 patients with GO and in none without GO, whereas the difference of C. pneumoniae IgG titres between patients with GO and pair-matched controls did not reach significance (P<0.57). Chlamydia pneumoniae-specific DNA was found in 10 of 11 GO tissue samples pre-treatment. Azithromycin therapy effectively reduced GO and C. pneumoniae IgM titres. In residual GO, C. pneumoniae-specific DNA remained detectable after 1 year in all GO tissue samples despite azithromycin treatment. The C.pneumoniae IgM titres correlated with GO scores. CONCLUSION: Chlamydia pneumoniae infection is highly prevalent in CsA-induced GO. The infection can persist over a long period in residual GO despite short-term azithromycin therapy. The results indicate that CsA immunosuppression enhances C. pneumoniae infection rates in non-cardiovascular tissue.