Methods. In the present study, we investigated the effect and molecular mechanism of the PPAR agonist, pioglitazone, on the progression of diabetic nephropathy in type 2 diabetic rats. Inflammatory markers including NF-B, MCP-1 and pro-fibrotic cytokines were determined by RT-PCR, western blot, immunohistochemical staining and EMSA. In addition, to evaluate the direct anti-inflammatory effect of PPAR agonist, we performed an in vitro study using mesangial cells.

Results. Treatment of OLETF rats with pioglitazone improved insulin sensitivity and kidney/body weight, but had a little effect on blood pressure. Pioglitazone treatment markedly reduced urinary albumin and MCP-1 excretion, and ameliorated glomerulosclerosis. In cDNA microarray analysis using renal cortical tissues, several inflammatory and profibrotic genes were significantly down-regulated by pioglitazone including NF-B, CCL2, TGFβ1, PAI-1 and VEGF. In renal tissues, pioglitazone treatment significantly reduced macrophage infiltration and NF-B activation in association with a decrease in type IV collagen, PAI-1, and TGFβ1 expression. In cultured mesangial cells, pioglitazone-activated endogenous PPAR transcriptional activity and abolished high glucose-induced collagen production. In addition, pioglitazone treatment also markedly suppressed high glucose-induced MCP-1 synthesis and NF-B activation.

Conclusions. These data suggest that pioglitazone not only improves insulin resistance, glycaemic control and lipid profile, but also ameliorates renal injury through an anti-inflammatory mechanism in type 2 diabetic rats.

Methods. We treated subtotally nephrectomized (SNX) and sham-operated, ad lib and pair-fed Sprague-Dawley rats with CIN (15 mg/kg day) or solvent (S) for 14 days p.o. and assessed whole body and tibia length gain, growth plate morphology, osseous front advance (OFA) (calcein staining) and chondrocyte proliferation rate [5-bromo-2'-deoxyuridine (BrdU) staining].

Results. Total body length gain did not differ after 7 and 14 days (SNX + CIN 2.9 ± 0.6, SNX + S 3.0 ± 0.7; sham + CIN 4.2 ± 0.4, sham + S 4.5 ± 0.4; sham pair-fed + CIN 3.3 ± 0.5, sham pair-fed + S 3.5 ± 0.6 cm/14 days; P = n.s.). Tibia length, the height of the total growth plate and the hypertrophic zone, OFA and chondrocyte proliferation rate were similar with CIN and S. Serum Ca²⁺ declined with CIN treatment; PTH was 61% lower in CIN- compared to S-treated SNX (P < 0.05). Food intake was similar, whereas body weight gain (21.6 ± 8.7 versus 12.7 ± 11.2 g) and body weight gain per food intake (141 ± 50 versus 77 ± 70 g/kg) improved in CIN- versus S-treated SNX animals (P < 0.05).

Conclusion. CIN treatment does not impact on growth plate chondrocyte function in uraemic rats, but improves food efficiency and body weight gain.

Methods. Six-month-old female NZB/W F₁ mice with active nephritis (albuminuria >100 mg/dL) were treated with rapamycin (3 mg/kg body weight) or saline once daily by oral gavage for 4 months. The effect of rapamycin on the severity of nephritis was evaluated by clinical manifestations, biochemical parameters, renal histology, immunohistochemistry and semi-quantitative gene expression studies.

Results. Treatment with rapamycin significantly decreased albuminuria, improved survival, diminished splenomegaly, preserved renal function and reduced serum anti-dsDNA antibody levels. Kidney sections from saline-treated mice revealed marked mesangial proliferation, tubular dilation with intra-tubular protein cast deposition and leukocytic infiltration of the interstitium. The rapamycin-treated mice, in contrast, had relatively mild histological changes in their kidneys. Rapamycin treatment also significantly reduced the amount of immune complex deposition in the glomeruli, suppressed the interstitial infiltration by T-cells, B-cells and macrophages as well as down-regulated the intra-renal expression of RANTES.

Conclusions. We conclude that rapamycin is effective in attenuating the severity of established nephritis in NZB/W F₁ mice_. The beneficial effects of rapamycin are mediated, at least in part, through inhibition of lymphoproliferation, reduced RANTES expression and decreased inflammatory cell infiltration in the kidneys. Rapamycin could be of therapeutic value in the treatment of human lupus nephritis.

Methods. Male Sprague-Dawley rats received CsA (15 mg/kg/day i.p.) and/or EPL (100 mg/kg/day p.o.) for 21 days. After 2 weeks, arterial, venous and urinary bladder catheters were implanted and the rats were trained to accept a restraining device allowing arterial blood sampling and direct measurement of BP and renal function. BP was measured on-line in conscious rats.

Results. CsA significantly increased systolic BP: 139 ± 4 versus 134 ± 2 mmHg, reduced body weight gain: –5 ± 6 versus 36 ± 7 g, glomerular filtration rate (GFR): 1.02 ± 0.16 versus 2.64 ± 0.27 ml/min, renal blood flow (RBF): 5.3 ± 2.4 versus 13.5 ± 2.1 ml/min and lithium clearance (C_Li+): 0.16 ± 0.04 versus 0.26 ± 0.07 ml/min compared to controls. These changes were prevented by simultaneous EPL treatment: systolic BP, 130 ± 4 mmHg; weight gain, 53 ± 7 g; GFR, 1.67 ± 0.26 ml/min; RBF, 12.3 ± 2.1 ml/min and C_Li+, 0.27 ± 0.03 ml/min. Analysis of kidney morphology after the CsA treatment showed hyaline vacuolization in tubules and vascular depositions in arterioles; these changes were less pronounced after combination therapy. No significant changes were seen regarding haemoglobin, haematocrit, plasma renin and vasopressin, plasma and urinary sodium, potassium, or osmolality.

Conclusions. MR blockade by EPL prevented short-term alterations in GFR, RBF and hypertension associated with CsA nephrotoxicity. We conclude that the aldosterone-MR pathway contributes markedly to the renal toxicity induced by this calcineurin inhibitor.

Methods. CsA-treated mice were injected with recombinant adenovirus expressing either COMP-Ang1 or LacZ. Histology, inflammatory, haemodynamic and fibrotic parameters, and signalling pathway were evaluated.

Results. Histologic examination showed that COMP-Ang1 significantly decreased CsA-induced tubular damage and tubulointerstitial fibrosis. CsA-induced increases in macrophage infiltration and expression of MCP-1 and ICAM-1 after CsA treatment were significantly reduced by COMP-Ang1. Treatment with COMP-Ang1 also decreased the CsA-induced increases in TGF-β1 and Smad 2/3 levels while increasing Smad 7 levels. Laser–Doppler sonographic findings and endothelial factor VIII staining revealed that COMP-Ang1 preserved the integrity of peritubular vasculature and intrarenal haemodynamics from the CsA-induced renal injury. COMP-Ang1 inhibited tubular cell apoptosis while increasing tubular cell proliferation in CsA-induced renal injury.

Conclusions. These results indicate that COMP-Ang1 exhibited a protective effect on damaged peritubular capillaries, haemodynamic alteration and inflammation in CsA-induced renal injury. Thus, COMP-Ang1 may be useful as a therapeutic and prophylactic agent for specific protection against endothelial dysfunction and inflammation.

Methods. The lysosomal enzyme cathepsin D was measured by ELISA and isolated by pepstatin-agarose affinity chromatography; N-acetyl-β-d-glucosaminidase (NAG) was assayed colorimetrically, as was the cytosolic enzyme lactate dehydrogenase (LDH). Cathepsin D, procathepsin D and CI-MPR were also detected by western blotting. No patient had a serum creatinine concentration >170 µmol/L. Soluble CI-MPR, isolated from fetal calf serum and bound to agarose, was used to probe cathepsin D for mannose-6-phosphate (M6P).

Results. Increased excretion of cathepsin D (mean = 44-fold) and NAG (mean = 12-fold) was found in FS patients: Dent's disease (n = 5), cystinosis (n = 4), Lowe syndrome (n = 3) and ‘autosomal dominant idiopathic FS’ (ADIF) (n = 2). Increased cathepsin D excretion was confirmed by western blotting; excretion of procathepsin D and LDH was not increased. When compared with control subjects, CI-MPR excretion was also increased in FS (n = 6). Thus, significantly increased excretion of lysosomal enzymes and CI-MPR was found in all cases of FS examined. Cathepsin D binding to CI-MPR-agarose was inhibited by M6P.

Conclusions. We conclude that underlying gene defects in FS may disrupt normal membrane trafficking of CI-MPR, leading to mistrafficking of lysosomal enzymes via a default pathway from the Golgi to the apical surface of proximal tubule cells rather than to lysosomes. Lysosomal enzymes are then secreted into the tubular fluid and excreted in the urine. This contrasts with the widely held view that cell necrosis is the cause of lysosomal enzymuria in renal disease. Moreover, cathepsin D in FS urine is M6P-tagged.

Methods. The study evaluated BS/GS patients for nitric oxide-dependent (FMD) and -independent vasodilation and intima-media thickness (IMT) of the carotid arteries compared with healthy subjects and essential hypertensive patients.

Results. The results showed the absence of IMT growth in BS/GS patients as cumulative mean-IMT and mean maximum-IMT levels in BS/GS did not differ from normotensives: 0.58 ± 0.09 mm versus 0.60 ± 0.09 and 0.67 ± 0.09 versus 0.70 ± 0.13 respectively, P = ns, but were significantly lower compared with hypertensive patients: 0.69 ± 0.13, P < 0.046 and 0.85 ± 0.19, P < 0.018, respectively. FMD was increased in BS/GS versus hypertensives or normotensive controls (10.8 ± 2.7% versus 6.5 ± 2.3 and 8.7 ± 1.9, P < 0.002 respectively) while endothelium-independent dilation did not differ (10.2 ± 3.6% versus 7.2 ± 1.9 and 8.2 ± 3.3, P = ns) between groups.

Conclusions. Our study in BS/GS provides to our knowledge the first clinical data that point to a direct proatherogenic role for Ang II. However, because the data are derived from findings in BS/GS and therefore are indirect, further studies in this and other models using more direct approaches should be pursued to demonstrate a direct proatherogenic effect of Ang II as well as further studies on Ang II type 2 receptor (AT2R) signalling that the spectrum of findings of this and other studies indicate as involved in the lack of vascular remodelling.

Methods. This study was conducted as a part of the Korean Longitudinal Study on Health and Aging (KLoSHA) that was designed as a population-based, prospective cohort-study in a population aged >65 years living in a satellite city of Seoul in Korea. Among 1 000 randomly selected subjects, 944 were able to complete the SF-36 questionnaires to measure HRQOL.We categorized the participants into five GFR groups: group 1: 90 mL/min/1.73 m² or more, group 2: 89–75 mL/ min/1.73 m², group 3: 60–74 mL/min/1.73 m², group 4: 45–59 mL/min/1.73 m² and group 5: less than 45 mL/min/ 1.73 m².

Results. Except for the general health perception and mental health scale, all the other scores of the SF-36 scales showed differences among five groups categorized according to GFR. However, the scores were significantly decreased only among participants with a GFR value of <45 mL/min/1.73 m², compared to the other four GFR groups. After adjustment, the physical component summary score was the lowest in participants with GFR values <45 mL/min/1.73 m². The dichotomized GFR factor with the criterion of 45 mL/min/1.73 m² was an independent predictor of poor physical HRQOL. Other factors, such as age, gender, duration of education, regular exercising habits, depression and a history of cardiovascular accident, were also predictors of HRQOL. A lower haemoglobin level was related to the mental component summary.

Conclusion. The renal function deduced to be an important predictor of HRQOL, even in the old age group. The moderately decreased renal function of 45 mL/min/1.73 m² GFR was the level at which HRQOL decreased in the elderly Korean population.

Methods. The present study included 2249 men and 2192 women without signs of kidney disease at baseline who were followed for 7 years from 1994 to 1995 in the Tromsø Study. Estimated glomerular filtration rate (eGFR) was calculated from the Modification of Diet in Renal Disease study equation. Gender-specific multiple linear regression analyses were used to assess predictors of change in eGFR (GFR).

Results. Change in eGFR, measured in ml/min/1.73 m²/year, was associated with systolic blood pressure (SBP) [β-value for a 10-mmHg increase in SBP, men = –0.14, 95% confidence interval (CI) = –0.18 to –0.09; women = –0.07, 95% CI = –0.11 to –0.03] and fibrinogen [β-value for 1 SD increase in fibrinogen, men (1 SD: 0.85 g/L) = –0.12, 95% CI –0.20 to –0.03; women (1 SD: 0.80) = –0.11, 95% CI –0.20 to –0.02]. High alcohol consumption in men and high physical activity in women predicted an increase in eGFR. Higher albumin/creatinine ratio was associated with a decline in eGFR in men only.

Conclusions. Some risk factors for change in GFR seem to be gender specific but both high SBP and high levels of fibrinogen contribute to a more rapid decline in GFR for both men and women.

Methods. We undertook a study of kidney function decline and physical function in 2544 women participating in the Nurses’ Health Study. Glomerular filtration rates (GFR) were estimated using the four-variable MDRD equation from plasma creatinine measured in blood collected in 1989 and 2000. Physical function was assessed by the Physical Function Sub-Scale (PFS) score of the Short Form 36 (SF-36) in a questionnaire administered in the year 2000. PFS scores have been shown to correlate well with direct measures of physical function.

Results. In the year 2000, the median age was 67 years, median body mass index (BMI) was 25.6 kg/m², 48.5% had hypertension and 5.8% had diabetes. There were 427 women (16.8%) who experienced an ≥25% decline in eGFR between 1989 and 2000. Median PFS in 2000 for those with an eGFR decline of ≥25% was 80 compared to a PFS score of 85 for those without (P < 0.001). In fully adjusted models, the presence of an eGFR decline of ≥25% was independently associated with a 3.5-point lower PFS score (95% CI –5.4 to –1.5). Also, an eGFR decline of ≥25% was independently associated with an increased odds ratio of being in the lowest quartile of PFS score (OR 1.37; 95% CI 1.04–1.81).

Conclusions. We conclude that an eGFR decline of ≥25% over 11 years is independently associated with lower physical function in women.

Methods. A prospective cohort of 2761 type 2 diabetic patients without significant dyslipidaemia and having at least one measurement of TC, LDL-C and HDL-C during 2.8 years of follow-up was analysed. The spline Cox regression model was used to derive hazard ratio (HR) curves of the spot urinary albumin:creatinine ratio (ACR) and the estimated glomerular filtration rate (eGFR) for dyslipidaemia, followed by standard Cox models to confirm the findings from the HR curves.

Results. Seven percent of the cohort developed high TC, 4.6% developed high LDL-C and 5.7% developed low HDL-C during follow-up. In multivariate analysis, the HR of ACR for high TC and high LDL-C increased rapidly and linearly from zero with no apparent threshold. Patients with macroalbuminuria (ACR ≥25 mg/mmol) were, respectively, 1.6- and 2.4 folds more likely to develop high TC and high LDL-C than those with normoalbuminuria at baseline. The HR of eGFR for low HDL-C increased rapidly with declining eGFR at <110 ml/min/ 1.73 m². Subjects with eGFR <60 ml/min/1.73 m² and ≥60–<110 ml/min/1.73 m², respectively, had 3.0-fold and 1.8-fold risks of low HDL-C compared to those with eGFR ≥110–<140 ml/min/1.73 m².

Conclusions. In type 2 diabetes, macroalbumninuria predicts high TC and high LDL-C, while reduced renal function, even within normal range, predicts low HDL-C.

Methods. A total of 156 patients with EH were enrolled and grouped according to albumin-to-creatinine ratio (ACR). Of these, 90 patients with EH underwent a 12-week antihypertensive trial with administration of benazepril, valsartan or both. Serum TGF-β₁, plasma angiotensin (Ang) II and urinary albumin were quantified by immunoassays.

Results. Serum TGF-β1, plasma Ang II and ACR were highly elevated in patients with EH (P < 0.01). There was a positive correlation between serum TGF-β1 levels and ACR (r = 0.53, P < 0.01). Significant decreases in TGF β1 and ACR were obtained in all groups at the end of 12-week antihypertensive therapy compared to the baseline values, with the combined group to a greater extent (P < 0.01). Plasma Ang II levels were significantly decreased in the benazepril group but increased in the valsartan group (P < 0.05) while no significant change was observed in the combined group.

Conclusions. TGF-β₁ is highly elevated and strongly associated with urinary albumin excretion in patients with EH. Treatment with benazepril or valsartan attenuates serum TGF-β₁ levels and microalbuminuria with the combined therapy receiving the greater effect. TGF-β₁ could be a potential surrogate marker in monitoring the development and progression of kidney damage in EH.

Methods. Non-azotemic patients were randomized to either a control group (n = 20) or an EPA group (n = 21). EPA capsules (2.4 g/day) were administered in the EPA group for 2 years. Twenty-four hours of urine was collected for the creatinine clearance (Ccr) measurement every year. At baseline and 24 months, fatty acid compositions in erythrocytes were measured and computerized tomographies were obtained for calculation of renal volume by the modified ellipsoid and volumetric methods.

Results. In the EPA group, the EPA concentration (1.80 ± 0.99 versus 4.40 ± 1.79 area%, P < 0.001) and the 3/6 ratio in the erythrocyte increased, but docosahexaenoic acid (DHA) (6.76 ± 1.19 versus 5.64 ± 1.45 area%, P < 0.010) concentration decreased. Ccr decreased by 8.5 ± 9.5 and 9.0 ± 13.0 ml/min/1.73 m²/2 years in the control and EPA groups, respectively (NS). The increases in renal volume calculated by either method were not significantly different between the two groups.

Conclusions. A beneficial effect of EPA on renal function and kidney volume in ADPKD patients could not be confirmed in the present study. Administration of EPA with DHA supplementation and/or longer intervention might be necessary to demonstrate preventive effects of 3-polyunsaturated fatty acids on progression of ADPKD.

Methods. An observational study of 201 consecutive adult patients was conducted; 100 were operated by the OPCAB and 101 by the ONCAB technique. All patients in each group were operated by a single, experienced surgeon. Fifteen pre-, intra- and postoperative variables that were repeatedly identified in previous studies as independent AKI risk factors were included in this analysis. AKI was defined as an increase of serum creatinine ≥50% or ≥0.3 mg/dL within 48 h and AKI severity was classified, according to current AKIN definitions.

Results. Significantly fewer OPCAB patients developed AKI compared to ONCAB (14.0 versus 27.7%; P = 0.03). OPCAB was associated with milder stages of AKI, whereas ONCAB patients had more severe AKI. Congestive heart failure and chronic kidney disease were independent risk factors for AKI. The OPCAB technique for CABG was identified as the only independent factor associated with lower incidence of AKI.

Conclusions. Using current AKI definitions and classifications, the OPCAB technique for CABG, which avoids CPB; was associated with a significantly lower rate and less severe AKI compared to ONCAB. The OPCAB technique was identified as the only modifiable and potentially protective factor against postoperative AKI.

Methods. Twelve healthy male individuals were included in a monocentre, randomized, single-blind, placebo-controlled, three-way crossover phase I study. Concurrently with their meals, participants received 4 x 2 tablets of SEV (800 mg), CC (500 mg) or placebo for 6 days with 1-week washout between the treatment periods. During the study, weekly blood samples were taken and 24-h urine was collected each day for measurement of calcium, magnesium, phosphorus, chloride and iPTH.

Results. Mean daily urinary phosphorus excretion was significantly lower in subjects undergoing SEV treatment compared to those taking placebo (P < 0.001). Mean daily total urinary excretion of calcium was significantly higher in CC-treated participants compared to those receiving placebo (P < 0.001). Mean 24-h calcium excretion during the 6 treatment days was 6.60 ± 2.62 mmol [265 ± 105 mg] (CC) versus 5.15 ± 2.16 mmol [206 ± 87 mg] (SEV) versus 4.95 ± 1.63 mmol [198 ± 65 mg] (Placebo). Taking into account nutritional calcium intake estimated from dietary records fractional calcium absorption was 8.7% (CC), 13.3% (placebo) and 14.8% (sevelamer).

Conclusion. Intake of calcium carbonate compared to placebo in contrast to sevelamer in healthy individuals was associated with increased total urinary calcium excretion indicating an increased calcium load due to increased intestinal calcium absorption.

Methods. This was a retrospective cohort study. Of 850 IgA nephropathy (IgAN) patients that were followed up in our renal centre, 32 received MMF (1–1.5 g/day) and 47 were treated with cyclophosphamide (CTX; 50–100 mg/day). All the patients also received prednisone. SP was defined as diffuse bilateral lung infiltrate with respiratory failure, and PCP was diagnosed by detecting organisms in sputum and bronchoalveolar lavage.

Results. Patients given MMF or CTX did not differ in their distribution of age, sex, renal function or prednisone dosage. However, 6 of the 32 patients developed SP around the third month after the initiation of MMF administration: 3 were diagnosed with PCP, 2 with suspected PCP and in the other PCP could not be excluded. SP did not occur in patients treated with CTX. Most SP cases (five of six) presented with abrupt onset and rapidly progressed to respiratory failure, from which four died. The deterioration of renal function was strongly associated with the occurrence of SP. Six patients (6 of 16) with chronic renal function impairment (eGFR < 60 ml/min/1.73 m²) developed SP while none of the patients with eGFR > 60 ml/min/1.73 m² did. Absolute lymphocyte counts decreased significantly in patients with eGFR < 60 ml/min/1.73 m² after 3 months of MMF treatment compared to the counts before MMF was initiated (1.71 ± 0.23 versus 2.43 ± 0.17 x 10⁹/l, P = 0.04). This effect was more pronounced in patients with SP, which had significantly lower counts than patients without SP (0.22 ± 0.04 versus 1.91 ± 0.20 x 10⁹/l, P = 0.001). The occurrence of SP or PCP in patients with chronically impaired renal function was also associated with lymphopenia.

Conclusions. This study is the first report of delayed SP including PCP following MMF plus corticosteroids in patients with IgAN. Chronically impaired renal function might be a risk factor for severe infection, and lymphocyte counts may serve as useful and convenient tools for monitoring the intendance of the occurrence of PCP. This finding and its risk factors need to be further evaluated.

Methods. In 34 patients, 24-h ambulatory BP (A&D TM2421) was measured at baseline and every 4 months for 1 year or until the need for renal replacement therapy. For each BP recording patients were classified as dippers or non-dippers based on the presence or absence of a nighttime reduction in both systolic and diastolic BP > 10%. Antihypertensive treatment aimed at an office BP < 120/80 mmHg. GFR was measured by the plasma clearance of ⁵¹Cr-EDTA and albuminuria was determined from 24-h collections.

Results. A total of 125 24-h BP recordings were made. Ten patients were constant dippers and five were constant non-dippers throughout the study whereas nineteen patients changed dipping status apparently at random. When analysing pairs of sequential recordings in the individual patient, non-dipper and dipper status remained unaltered in 25 (27%) and 32 (35%) of comparisons, respectively, whereas it was inconsistent in 34 (38%) of cases. No correlation between dipper status and GFR, decline in renal function, degree of albuminuria or BP level could be demonstrated.

Conclusions. The consistency of circadian BP variation seems to be poor in CKD stages 3–5 and single measurements of 24-h ambulatory BP are therefore probably inadequate for the evaluation of dipping status.

Methods. We analysed cross-sectional data from 7389 outpatient adults, who were referred by general practitioners for routine blood testing between June 2006 and June 2007. Glomerular filtration rate (eGFR) was estimated by the abbreviated Modification of Diet in Renal Disease (MDRD) equation. Multivariable linear regression analysis was used to identify factors independently associated with haemoglobin concentrations across eGFR categories as the main outcome.

Results. Of the 7389 participants included in the analytic cohort 2221 (30.1%) participants had eGFR ≥90 mL/min/m², 4310 (58.3%) 60–89 mL/min/m² and 858 (11.6%) <60 mL/min/m². There were significant, graded, increases in high sensitivity C-reactive protein (hs-CRP) and haemoglobin concentrations across eGFR categories independent of age, gender, plasma glucose and lipids (P < 0.0001 for trends). In the multivariable regression analysis, increased hs-CRP concentrations were independently associated with lower haemoglobin concentrations at different stages of eGFR (P < 0.0001 for all). Other independent predictors of lower haemoglobin were older age, female gender and lower eGFR.

Conclusions. Our findings suggest that increased plasma hs-CRP concentrations are independently associated with anaemia in the setting of decreased kidney function in a large cohort of unselected adult outpatients.

Methods. Total calcium (TCa), ionized calcium (iCa²⁺), magnesium, phosphate, albumin and bicarbonate were collected from 60 HD patients to derive the formula. A validation set of 237 stable HD patients was then examined, and subjects were classified as hyper-, hypo- and normocalcaemic based on the iCa²⁺. Agreement of the new formula was calculated with iCa²⁺ as the gold standard, using the intraclass correlation coefficient (ICC). This was compared to the agreement between iCa²⁺ and the following: uncorrected total serum calcium (TCa), the conventional correction formula, the Orrell formula and the Clase formula.

Results. Using multiple linear regression the following formula was derived: corrected total calcium (mmol/L) = TCa (mmol/L) + 0.01 [30 (g/L) – albumin (g/L)]. The new formula had superior agreement compared to all of the other formulae. There was a statistically significant greater agreement between the new formula and the iCa²⁺ as compared to the conventional formula (P < 0.01). However, the new formula did not significantly outperform the Orrell formula, the Clase formula or Total calcium.

Conclusions. The use of our simple new formula should enable more appropriate decision making compared to the conventional formula in the highly complex HD population.

Methods. This study was performed on formalin-fixed paraffin-embedded archival tissues of 21 SHPT glands from haemodialysis (n = 19) and kidney transplanted (n = 2) patients submitted to surgical parathyroidectomy. For control, eight normal human parathyroid glands (NPG) encountered in surgical specimens of total thyroidectomy were used. We evaluated the immunohistochemical expression of the proliferation cell marker Ki67. Angiogenesis was evaluated by immunohistochemistry staining with anti-endoglin (CD105) antibody in 21 SPH and 5 NPG by stereological analysis. Levels of b-FGF and VEGF were determined by semi-quantitative analysis in 21 SPH and 8 NPG.

Results. The SHPT patients present a mean iPTH of 1314 ± 750 pg/ml, a corrected serum calcium of 10.3 ± 1.2 mg/dl and a serum phosphorus of 6.1 ± 1.4 mg/dl. SHPT glands displayed a significantly higher immunoreactivity against Ki67, compared to NPG. With CD105, a significantly higher number and volume of microvessels were observed in SHPT compared to NPG. Both VEGF and b-FGF expression were increased in SHPT compared to NPG. Using the predefined subdivision into negative and positive only the b-FGF expression was significantly increased in the SHPT glands compared to NPG.

Conclusion. These results suggest that PTGs in this group of patients with SHPT have a significantly higher number of vessels expressing CD105, which has been reported to preferentially label activated endothelial cells associated with angiogenesis. SHPT glands have a significantly increased expression of b-FGF compared to NPG. VEGF-A expression is also increased in the examined SHPT glands but could be less relevant for angiogenesis.

Methods. The Ca²⁺-PTH curve was evaluated in 10 haemodialysis patients, with baseline intact PTH levels >300 pg/ml in two haemodialysis sessions, one before and the other after (range, 9–22 weeks) cinacalcet treatment. In each session a 2-h low-dialysate Ca²⁺ concentration was used to induce hypocalcaemia and maximally stimulate PTH secretion, followed immediately by a 2-h high-dialysate Ca²⁺ concentration to induce hypercalcaemia and maximally inhibit PTH secretion.

Results. Significant decreases in ionized Ca²⁺ and intact PTH were observed following cinacalcet treatment. Cinacalcet treatment also led to a decrease in the set point for Ca²⁺ and to a leftward shift of the Ca²⁺-PTH curve. Significant differences were present in all segments of the Ca²⁺-PTH curves.

Conclusion. The pathological rightward shift of the Ca²⁺-PTH curve seen in many HPT patients may be reversed by cinacalcet treatment.

Methods. Eighty-six patients were assigned to a standard care (CTRL) group or were prescribed two 125-ml packs of Renilon 7.5® daily for 3 months (SUPP). Dietary intake, serum (S) albumin, prealbumin, protein nitrogen appearance (nPNA), C-reactive protein, subjective global assessment (SGA) and quality of life (QOL) were recorded at baseline and after 3 months.

Results. While intention to treat analysis (ITT) did not reveal strong statistically significant changes in dietary intake between groups, per protocol (PP) analysis showed that the SUPP group increased protein (P < 0.01) and energy (P < 0.01) intakes. In contrast, protein and energy intakes further deteriorated in the CTRL group (PP). Although there was no difference in serum albumin and prealbumin changes between groups, in the total population serum albumin and prealbumin changes were positively associated with the increment in protein intake (r = 0.29, P = 0.01 and r = 0.27, P = 0.02, respectively). The SUPP group did not increase phosphate intake, phosphataemia remained unaffected, and the use of phosphate binders remained stable or decreased. The SUPP group exhibited improved SGA and QOL (P < 0.05).

Conclusion. This study shows that providing maintenance haemodialysis patients with insufficient intake with a renal-specific oral supplement may prevent deterioration in nutritional indices and QOL without increasing the need for phosphate binders.

Materials and methods. In study I, the relative influence of the various parts of the ECC was evaluated by measuring the expression of CD62p, platelet aggregation and levels of PF4 and serotonin at various sampling points. In study II, low-molecular-weight heparin (LMWH) was administered 10 min before the actual start of HD, in order to separate the effects from LMWH and the ECC on platelet activation.

Results. In study I, CD62p expression increased across the entire length of the ECC, including the roller pump and dialyser (median at t₅ from 26% to 43%, P = 0.008; median at t₃₀ from 28% to 48%, P = 0.007). Increments in PF4 and aggregation of platelets were relatively modest. Platelet serotonin content, which was below reference values in healthy controls, and plasma serotonin concentration, which was above reference values, did not change. In study II, PF4 levels increased markedly after the injection of LMWH (from 12 IU/ml at t_–10 to 75 IU/ml at t₀, P = 0.018), whereas CD62p expression remained stable until the start of HD.

Conclusions. Platelet activation, as measured by the up-regulation of CD62p, is an early process, occurring not only within the dialyser, but across the entire length of the ECC. As CD62p remained unaltered after the administration of LMWH 10 min before the actual start of HD, this kind of activation is independent of LMWH. Considering PF4 however, a sharp increment was observed after the administration of LMWH and before the start of HD. This finding suggests that the PF4 release observed early in clinical HD is largely independent from the ECC, and is probably the result of LMWH-induced detachment from the endothelium. As the platelet serotonin content was relatively reduced and the plasma serotonin levels were elevated, platelets from chronic HD patients might be depleted due to chronic repetitive activation. Based on these data, it appears first, that PF4 is an inferior marker of platelet activation in clinical HD and second, that LMWH is a major contributor to HD-induced bio-incompatibility.

Methods. In a double-blind randomized placebo-controlled design, patients with documented CVD, treated with HD for a minimum of 6 months, were randomized to treatment with n-3 PUFA or a control treatment (olive oil). A dietary intake of n-3 PUFA was assessed with a dietary questionnaire. Plasma lipids and lipoproteins and the content of n-3 PUFA in serum phospholipids were measured at baseline and after 3 months.

Results. Two hundred and six patients were included. Serum phospholipid levels of n-3 PUFA were significantly higher in patients reporting a high fish intake compared to patients reporting a low fish intake. After 3 months, a significant decrease was seen in serum triglycerides in the n-3 PUFA group compared to the control group (P = 0.01). No significant effect was seen on total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, Lp(a) or apoB.

Conclusion. In patients treated with HD, consumption of fish increases levels of n-3 PUFA. Additional supplementation with n-3 PUFA for 3 months further increases levels of n-3 PUFA and lowers serum triglycerides, but does not significantly affect other plasma lipids or lipoproteins.

Methods. Proteins were eluated from the different LDL-A columns and investigated with 2D electrophoresis combined with mass spectrometry methods. In parallel, we quantified the plasma protein loss from patients treated with double-filtration plasmapheresis (DFPP; n = 9), direct adsorption of lipoproteins (DALI; n = 5) or heparin-induced extracorporeal LDL precipitation (HELP; n = 7) with routine laboratory methods and western blots.

Results. Proteomic analyses of the column-bound proteins revealed a column-type-dependent loss with the highest number of protein spots in DALI-treated patients (1001 ± 36), followed by HELP (881 ± 25) and DFPP (535 ± 20). More than 70 functional proteins were identified. These proteins are involved in the coagulation pathway (e.g. kininogen1) and have adhesive (e.g. fibronectin), rheological (e.g. fibrinogen) and immunological/inflammatory properties (e.g. complement components). Quantification with western blot analyses demonstrated a significant depletion (P < 0.01) of these proteins comparing serum samples before and after the column with a systemic lowering in patients’ serum.

Conclusions. These data reveal strong interaction between column and serum proteins during LDL-A. The clearance of proteins with adhesive, rheological, and inflammatory characteristics may have beneficial effects on microcirculation and reduce chronic inflammation but may also concomitantly induce side effects such as an increased bleeding risk.

Methods and results. Among 142 patients who were about to start RRT, 60 who were asymptomatic underwent coronary evaluation by multi-slice computed tomography (MSCT) and/or coronary angiography (CAG). CAG diagnosed 35 patients (43.8%) as CAS positive and 27 of them had multi-vessel disease. Factors associated with CAS were smoking, elevated cTnT, low ABPI and high IMT. Moreover, the severity of CAS was associated with smoking, cTnT and ABPI. Stepwise logistic regression analyses revealed that cTnT was a powerful predictor of asymptomatic multi-vessel CAS. Receiver operating characteristic analysis documented the usefulness of cTnT as a screening tool with a cut-off point 0.05 ng/ml. The optimal screening tool for multi-vessel CAS was cTnT (sensitivity, 92.6%; 95% CI, 82.7–99.9; specificity, 63.6%; 95% CI, 47.2–80.0).

Conclusion. We concluded that cTnT should be measured as part of a strategy for detecting asymptomatic CAS, especially multi-vessel disease in patients with CKD at the start of RRT.

Methods. A total (prevalent and incident) of 313 patients from four dialysis units were included. The QIA was based on a multifaceted strategy involving collection of haemodialysis clinical performance measures every 6–8 months, feedback about results, improvement plans and benchmarking, and it was tested in a 3-year prospective interventional study. Two timepoints of clinical performance measures were considered for evaluating the QIA: baseline (February 2003, pre-QIA) and final (February 2006, post-QIA).

Results. Centres showed significant improvement in percentage of patients with haemoglobin <11 g/dl, mean haemoglobin; percentage of patients with Kt/v <1.2, mean Kt/v; percentage of patients with phosphorous >5.5 mg/dl, mean phosphorous; percentage of patients with calcium phosphate product >55, mean calcium phosphate product; and percentage of patients with ferritin <200 ng/ml, mean ferritin. No change was observed in percentage of patients with haemoglobin between 11 and 13 g/dl, erythropoietin consumed; percentage of patients with ferritin <100 ng/ml; percentage of patients with ferritin >800 ng/ml; percentage of patients with albumin <3.5 g/dl, mean albumin; or percentage of native arteriovenous fistula. The percentage of patients with haemoglobin >13 g/dl was increased.

Conclusions. Quality-improvement strategies can help improve haemodialysis performance for anaemia, dialysis dose and bone metabolism. The importance of assessing patients with high haemoglobin level should be stressed.

Methods. We retrospectively reviewed laboratory and demographic data from 1499 patients receiving hemodialysis in 15 units operated by the same dialysis provider. We performed univariate and multivariate logistic regression analysis to determine predictors of an average 3-month hemoglobin level below or above the target interval of 11.0–12.5 g/dL. To explain the effect of facility on anemia performance, we calculated correlations between measures of EPO responsiveness and the probability of achieving the target interval by facility.

Results. Patients above the target hemoglobin range demonstrated an association with parathyroid hormone (PTH) (OR = 0.96 per 100 pg/mL increase), female gender (OR = 0.68), EPO protocol use (OR = 0.94 per 10% increase in use) and facility (range of OR = 0.26–2.59 for 15 participating sites). Patients below the target hemoglobin range demonstrated an association with CRP (OR = 1.10 per mg/L increase), PTH (OR = 1.07 per 100 pg/mL increase), iron deficiency (OR = 1.07 per 10% increase), EPO protocol use (OR = 0.89 per 10% increase in use), iron protocol use (OR = 0.93 per 10% increase in use) and facility (range of OR = 0.58–3.41 over 15 units). EPO index (r = 0.71), EPO dose (r = 0.73), hemoglobin (r = –0.60) and EPO per unit weight (r = 0.76) were significantly correlated with the probability of achieving the target hemoglobin by facility.

Conclusions. The facility significantly influences the outcome of anemia management in patients with ESRD. In part, this is due to the patients’ EPO responsiveness, which may be influenced by facility care patterns.

Methods. Patients from a prospective multi-centre cohort study among ESRD patients starting with their first dialysis treatment [the Netherlands Co-operative Study on the Adequacy of Dialysis-2 (NECOSAD-II)] with complete data on these risk factors were included (n = 815, age: 59 ± 15 years, 60% men, 65% HD). Hazard ratios (HR) were calculated for all-cause mortality in 7 years of follow-up. The presence of interaction between the three risk factors was examined, based on additivity of effects.

Results. Of all patients, 10% only suffered from PEW (1–5 on the 7-point subjective global assessment), 11% from inflammation (CRP ≥10 mg/L), 14% from CVD and 22% had any combination of two components. Only 6% of the patients had all three risk factors. Patients with either PEW (HR: 1.6, 95% CI: 1.3–2.0), inflammation (1.6, 1.3–2.0) or CVD (1.7, 1.4–2.1) had an increased mortality risk. In patients with all three risk factors, the crude mortality rate of 45/100 person-years was 16 deaths/100 person-years higher than expected from the addition of the solo effects of PEW, inflammation and CVD. The relative excess risk due to interaction was 2.9 (95% CI: 0.3–5.4), implying additive interaction. After adjustment for age, sex, treatment modality, primary kidney diseases, diabetes and malignancy the HR for patients with all three risk factors was 4.8 (95% CI: 3.2–7.2).

Conclusions. The concurrent presence of PEW, inflammation and CVD increased the mortality risk strikingly more than expected, implying that PEW interacts with inflammation and CVD in dialysis patients.

Methods. A new bioimpedance spectroscopy device (BCM—Body Composition Monitor) was selected that allows quantitative determination of the deviation in hydration status from normal ranges (HS). Pre-dialysis systolic blood pressure (BPsys) and HS was analysed in 500 haemodialysis patients from eight dialysis centres. A graphical tool (HRP—hydration reference plot) was devised allowing HS to be combined with measurements of BPsys enabling comparison with a matched healthy population (n = 1244).

Results. Nineteen percent of patients (n = 95) were found to have normal BPsys and HS in the normal range. Approximately one-third of patients (n = 133) exhibited reasonable control of BPsys and fluids (BPsys <150 mmHg and HS <2.5 L). In only 15% of patients (n = 74) was hypertension observed (BPsys >150 mmHg) with a concomitant HS >2.5 L (possible volume-dependent hypertension). In contrast, 13% of patients (n = 69) were hypertensive with HS <1.1 L (possible essential hypertension). In 10% of patients (n = 52), BPsys <140 mmHg was recorded despite HS exceeding 2.5 L.

Conclusion. Our study illustrated the wide variability in BPsys regardless of the degree of HS. The HRP provides an invaluable tool for classifying patients in terms of BPsys and HS and the proximity of these parameters to reference ranges. This represents an important step towards more objective choice of strategies for the optimal treatment of hypertension and FO. Further studies are required to assess the prognostic and therapeutic role of the HRP.

Methods. The analysis included all incident PD patients enrolled in the UKRR from 1999 to 2004. The event of interest was technique failure. For both the ANN and LR analyses a bootstrap approach was used: the data were divided into 20 random training (75%) and validation (25%) sets. Models were derived on the latter and then used to make predictions on the former. Predictive accuracy was assessed by area under the ROC curve (AUROC). The 20 AUROC values and their standard errors were then averaged.

Results. There were 3269 patients included in the analysis with a mean age of 59.9 years and a mean observation time of 430 days. Of the patients, 38.3% were female and 90.8% were Caucasian. 1458 patients (44.6%) suffered technique failure. The AUROC for the ANN model was 0.760 ± 0.0167 and the LR model was 0.709 and 0.0208. (P = 0.0164)

Conclusions. Using UKRR data, both ANN and LR models predicted early PD technique failure with moderate accuracy. In this study, an ANN outperformed an LR-based approach. As the scope and the completeness of the UKRR increases, the question of whether more sophisticated ANN models will perform even better remains for further study.

Methods. 50 patients were randomized to either 2.27% glucose or icodextrin (n = 28) for a long exchange following a month run in. Blood samples were obtained at –1, 0, 3 and 6 months, coincident with measurements of urine volume and fluid status.

Results. In both randomized groups, a significant correlation between the fall in ECFv and the decline in urine volume was observed (P = 0.001), although the relative drop in urine volume for patients randomized to icodextrin tended to be less. At baseline, ANP was higher in patients with proportionately more ECFv for a given body water or height. Icodextrin patients had non-significantly higher ANP levels at baseline, whereas by 3 (P = 0.026) and 6 months (P = 0.016) these differed between groups due to divergence. There was a correlation between increasing ANP and reduced ECF at 3 months, r = –0.46, P = 0.007, in patients randomized to icodextrin, but not glucose. There were no relationships between fluid status and any inflammatory markers at any point of the study, with the exception of albumin at baseline, r = –0.39, P = 0.007. Amylase activities at –1 month and baseline were highly correlated, r = 0.89, P < 0.0001. Within patients, concentrations of icodextrin metabolites were highly correlated; the only predictor of between-patient variability on multivariate analysis was body weight. There was no relationship between plasma concentrations of icodextrin metabolites and any of the other clinical parameters, including change in daily ultrafiltration, urine volume, fluid or inflammatory status.

Conclusions. This analysis supports observational data that changes in fluid status are associated with changes in urine volume. Icodextrin was not associated with a greater fall in urine output despite its larger effect on ECFv. Changes in fluid status could not be explained or did not appear to influence systemic inflammation. Nor can they be explained by individual variability in plasma concentrations of icodextrin that are in turn inversely proportional to the volume of distribution.

Methods. We studied the peritoneal transport characteristics of 50 consecutive new PD patients at 4 and 52 weeks after PD. Peritoneal permeability will be determined by the standard peritoneal equilibration test (PET). BMP-7 in PD effluent (PDE) at mRNA and protein level at 4 weeks was quantified.

Results. At 4 weeks, the mRNA expression of BMP-7 in PDE significantly correlated with peritoneal transport characteristics, including the dialysate-to-plasma creatinine ratio at 4 h (D/P4) (r = 0.422, P = 0.015) and mass transfer area coefficient (MTAC) of creatinine (r = 0.457, P = 0.008). The PDE BMP-7 level by ELISA also had marginal correlation with D/P4 (r = 0.287, P = 0.072) and MTAC creatinine (r = 0.287, P = 0.073), although the result did not reach statistical significance. For the subgroup of patients who remained free of peritonitis, the PDE BMP-7 level by ELISA had significant correlation with the change in D/P4 (r = 0.441, P = 0.017) and MTAC creatinine in 52 weeks (r = 0.415, P = 0.025). The PDE BMP-7 level remained independently associated with the change in peritoneal transport adjusting for age, sex, serum C-reactive protein and PDE transforming growth factor-beta level. In patients who had peritonitis during the study period, the PDE BMP-7 level did not affect the change in peritoneal transport.

Conclusion. We find that the peritoneal BMP-7 level correlates with peritoneal transport characteristics, and a high PDE BMP-7 level is associated with a gradual increase in peritoneal transport parameters with time. It remains unclear, however, whether this effect is beneficial, and the therapeutic role of exogenous BMP-7 on peritoneal transport requires a further study.

Methods. We performed a systematic review of the literature to identify all of the different definitions and diagnostic techniques to identify DGF.

Results. We identified 18 unique definitions for DGF and 10 diagnostic techniques to identify DGF.

Conclusions. The utilization of heterogeneous clinical criteria to define DGF has certain limitations. It will lead to delayed and sometimes inaccurate diagnosis of DGF. Hence a diagnostic test that identifies DGF reliably and early is necessary. Heterogeneity, in the definitions used for DGF, hinders the evolution of a diagnostic technique to identify DGF, which requires a gold standard definition. We are in need of a new definition that is uniformly accepted across the kidney transplant community. The new definition will be helpful in promoting better communication among transplant professionals and aids in comparing clinical studies of diagnostic techniques to identify DGF and thus may facilitate clinical trials of interventions for the treatment of DGF.

Design, setting, participants and measurements. We examined the utility of cysC as compared to other traditional measures of kidney function, including serum creatinine and 24-h urine for creatinine clearance, in the evaluation of kidney function in 51 consecutive live kidney donors both prior to and following unilateral nephrectomy.

Results. This is the largest experience reported in the living kidney donor population. We found that living kidney donors at our centre lost ~30–35% of kidney function following unilateral nephrectomy and this remained stable >1 year. Furthermore, we observed that cysC correlated well with all other markers of kidney function and detected acute changes in kidney function immediately post-nephrectomy.

Conclusions. Overall, however, cysC did not confer any advantage with respect to preoperative assessment of kidney function or for monitoring following live kidney donation as compared to more traditional measures.

Methods. We compared the outcomes of 17 patients with HSP who received 19 renal transplants with those of 38 controls matched for time of transplantation, age, gender and source of donor. The mean post-transplant follow-up was 109 ± 99 months for HSP patients and 110 ± 78 months for controls.

Results. The actuarial 15-year patient survival was 80% in HSP patients and 82% in controls, and the death-censored graft survival was 64% in HSP patients and in controls. The risks of acute rejection, chronic graft dysfunction, arterial hypertension and infection were not different between the two groups. In eight grafts (42%) recurrence of HSP nephritis was found (0.05/patient/year). In spite of therapy, one patient died and four eventually restarted dialysis respectively 10, 32, 35 and 143 months after renal transplant. Seventy-one percent of grafts transplanted in patients with necrotizing/crescentic glomerulonephritis of the native kidney had HSP recurrence in comparison to 12% of recurrences in patients with mesangial nephritis (P = 0.05)

Conclusions. Long-term patient and allograft survival of HSP patients was good. However, 42% of HSP patients, particularly those with necrotizing/crescentic glomerulonephritis of the native kidneys, developed a recurrence of HSP nephritis that eventually caused the loss of the graft function in half of them.

Methods. Five investigators were willing to participate and provided IPD. The outcomes of interest were GF, GR and CAN. Subjects with at least one of these were classified as having poor outcomes. Heterogeneity of gene effects was assessed. Multiple logistic regression was applied to assess gene effects, adjusting for clinical variables such as HLA matching and age.

Results. One-thousand and eighty-seven subjects were included in the IPD meta-analysis. Pooled results showed no evidence of heterogeneity and indicated that the strongest variables determining poor outcomes are HLA mismatching (OR = 1.6–1.8 for ≥3 HLA-A, -B, -DR mismatches compared with those with <3 mismatches) and age (OR = 1.2–1.4 for age 45 years or more). Incremental information on risk of a poor outcome is provided by the TGF-β1c10 polymorphism (OR = 1.5, P = 0.034, 95% CI: 1.0–2.2 for TC genotype compared to TT genotype). Haplotypes of TGF-β1 at c10 and c25 were inferred and the C-C haplotype was a marker of a poor outcome (OR = 1.3, P = 0.177, 95% CI: 1.0–2.3). Three polymorphisms of the IL-10 gene at –1082, –819, –592 are in strong linkage disequilibrium with each other (correlation coefficients: 0.6–1) and inferred haplotypes between these three loci show some association, with ACC increasing the risk of poor events com- pared to GCC (OR = 1.3, P = 0.044, 95% CI: 0.9–1.6).

Conclusion. Pooled results to date suggest possible association between both the TGF-β1 c10 polymorphism and a 3-SNP-haplotype of IL-10 and poor outcomes in renal transplantation, but this needs to be confirmed in larger studies.