Methods. Wistar rats were subjected to left nephrectomy and 90-min right kidney occlusion. In controls, the blood flow was restored without intervention. In postconditioned rats, complete reperfusion was preceded by 3 min, 6 min and 12 min of reperfusion in a consecutive sequence, each separated by 5 min of reocclusion. Animals were studied for 48 h. Mitochondrial respiratory chain function, rate of hydroperoxide production and carbonyl proteins were measured at the end of postconditioning and 24 h and 48 h after reperfusion.

Results. BUN and creatinine significantly decreased in the postconditioning group as compared to control rats. Mitochondrial respiratory function was significantly impaired in control rats, mainly at the level of Complex II. Postconditioning significantly reduced this mitochondria impairment. The rate of mitochondrial peroxide production was higher in the control group than in the protected group at the end of postconditioning reperfusion. Moreover, mitochondrial protein oxidation was significantly higher in control rats than in the postconditioning group at the end of reperfusion.

Conclusions. In the present study, postconditioning reduced renal functional injury and reduces mitochondria respiratory chain impairment, mitochondria peroxide production and protein damage.

Methods. Human umbilical vein endothelial cells (HUVECs) were exposed to therapeutic concentrations of EPO. The expression and metabolic activity of dimethylarginine dimethylaminohydrolase II (DDAH II), the enzyme that degrades ADMA, was evaluated. Following subcutaneous administration of EPO to Balb/c mice for 10 weeks, serum ADMA concentrations were determined. Systolic blood pressure was measured noninvasively. Urinary nitrite and nitrate (NOx) concentrations were assessed by Griess assay. Protein expression of DDAH and NOS in livers and kidneys was measured by western blotting.

Results. EPO suppressed ADMA elaboration by HUVECs. Systolic blood pressure and serum concentrations of ADMA were significantly elevated in EPO-treated mice. The protein expression of DDAH I in the kidney and liver was upregulated while hepatic expression of DDAH II was decreased and renal DDAH II expression remained unchanged by EPO administration. However, EPO augmented urinary NOx concentrations as well as the expression of NOS 1 and NOS 2 in the kidney.

Conclusion. In spite of elevating serum ADMA concentrations, EPO does not appear to compromise overall NO generation in Balb/c mice.

Methods. We evaluated therapeutic effects of CEPO using a rat unilateral ureteral obstruction model.

Results. CEPO decreased tubular apoptosis and -smooth muscle actin (SMA) expression in the absence of polycythaemia, while the untreated obstructed kidneys exhibited increased tubular apoptosis with expanded (SMA) expression. While EPO treatment similarly inhibited tubular apoptosis and SMA expression, EPO treatment increased Hb concentrations and induced a wedge-shaped infarction.

Conclusion. We established a therapeutic approach using CEPO to protect against tubulointerstitial injury. The therapeutic value of this approach warrants further attention and preclinical studies.

Methods. The PTGs of Sprague–Dawley rats, which had been 5/6-nephrectomized and fed a high-phosphate diet for 12 weeks, were treated with two consecutive direct injections (DI) of calcitriol, maxacalcitol, paricalcitol, doxercalciferol or phosphate-buffered saline containing either 0.01% or 90% ethanol (0.01-ET or 90-ET, respectively). Laboratory data, including serum levels of intact parathyroid hormone (intact-PTH), were obtained before and after the treatments. The PTGs were excised 24 h after the final injection and evaluated for PTC apoptosis using light and electron microscopy, terminal deoxynucleotidyl transferase-mediated dUTP nick end-labelling (TUNEL) method and DNA electrophoresis.

Results. Treatment with any of the vitamin D metabolites and 90-ET significantly decreased the serum intact-PTH level, but only the latter significantly decreased the serum Ca level. Either treatment markedly increased the number of TUNEL-positive PTCs, but not in PTG treated with 0.01-ET. In PTGs treated with DI of any vitamin D metabolites was there ladder formation on DNA electrophoresis, as well as the characteristic morphological features of apoptosis in both the light and electron microscopic studies.

Conclusions. DI of vitamin D metabolites may be effective in controlling not only the PTH level, but also PTG hyperplasia, in advanced SHPT by, at least in part, apoptosis-induced cell death. Our study was performed in rats.

Methods. Activation of signalling molecules was assessed by western blotting using phospho-specific antibodies. To specifically interfere with signalling cascades, porcine proximal tubular cells (LLC-PK/AT1) were infected with recombinant replication-deficient adenoviruses. In other experiments, specific kinase inhibitors were used. The SMA synthesis was assessed by western blotting or immunofluorescent staining of cellular SMA. To assess the regulation of the SMA promoter, tubular cells were transiently transfected with a 785 bp SMA promoter–luciferase reporter construct and vectors interfering with the Smad pathway.

Results. Blocking ERK1,2 activation with PD98059 or p38 MAPK with SB 203580 potently inhibited the TGFβ-induced SMA synthesis in renal tubular cells. Adenoviral expression of dominant negative (DN) p38β but not of p38 potently inhibited SMA expression. Furthermore, adenoviral expression of DN MKK6b but not of DN MKK3b caused a substantial inhibition of the TGFβ effect, confirming the role of p38β in the regulation of TGFβ-induced SMA expression. Finally, inhibiting the Smad pathway with adenovirally delivered Smad7 and DN Smad3 also blocked TGFβ-induced SMA synthesis.

Conclusion. TGFβ-induced SMA expression is regulated by the coordinated activation of a complex system of parallel MAPK and Smad signalling pathways in renal proximal tubular cells during epithelial–mesenchymal transdifferentiation.

Methods. Female rats were investigated 2 weeks after induction of DM by streptozotocin administration. Kidneys were examined by immunohistochemisty and semiquantitative immunoblotting.

Results. We demonstrated that the protein expression of renal AQP2, Ser-256 phosphorylated AQP2, AQP3, β- and -ENaC (but not -ENaC) increased consistently with an increased AVP response. In contrast, there were no significant changes in the relative apical targeting of β-, - and -ENaC, and the shift in the molecular weight of -ENaC from 85 kDa to 70 kDa was not observed despite increased plasma aldosterone levels. These results were supported by changes in the functional data showing increased solute-free water reabsorption, increased fractional excretion of sodium and an unchanged ratio of potassium to sodium in the urine.

Conclusions. The data demonstrate that diabetic kidneys have a reduced sensitivity to the anti-natriuretic action of elevated plasma aldosterone levels with no relative increase in ENaC subunit apical targeting, whereas there is increased expression of β- and -ENaC, which alone may play a role in the increased sodium reabsorption in the kidney in DM.

Methods. We measured the effects of atorvastatin (AS) on renal function in two randomized, placebo-controlled, double-blinded and crossover studies in healthy man. In an acute trial (Study 1), 19 subjects received either 80 mg AS as a single dose or placebo. In a short-term trial (Study 2), 20 subjects received either 80 mg AS or placebo daily for 4 weeks. In both studies glomerular filtration rate (GFR), renal plasma flow (RPF), plasma concentrations of angiotensin II (Ang II), renin (PRC), atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), aldosterone (Aldo), vasopressin (AVP) and blood pressure (BP) were determined.

Results. In Study 1 AS decreased fractional excretion of sodium (FE_Na) significantly (P = 0.035), but very modestly, and reduced diastolic BP (P = 0.024). Apart from this, we found no significant differences in GFR, RPF, tubular function and vasoactive hormones in either Study 1 or 2.

Conclusions. An acute dose of AS decreased FE_Na and DBP in healthy humans. The reduction in fractional urinary sodium excretion was very modest and transitory, and most likely secondary to the fall in diastolic blood pressure (DBP). However, renal haemodynamics, tubular function, vasoactive hormones and blood pressure were unchanged during short-term statin treatment in healthy man.

Methods. In 2005, all patients admitted to the medical, surgical or neurological intensive care unit (ICU) of a university hospital were reviewed. A 1:2 matched case-control study was performed, defining cases as patients who developed a serum sodium ≥150 mmol/l in the ICU.

Results. One hundred and thirty cases with ICU-acquired hypernatraemia (141 ± 3 to 156 ± 6 mmol/l) were compared to 260 controls. Sepsis (9% versus 2%), hypokalaemia (53% versus 34%), renal dysfunction (53% versus 13%), hypoalbuminaemia (91% versus 55%), the use of mannitol (10% versus 1%) and use of sodium bicarbonate (23% versus 0.4%) were more common in cases (P < 0.05 for all) and were independently associated with hypernatraemia. During the development of hypernatraemia, fluid balance was negative in 80 cases (–31 ± 2 ml/kg/day), but positive in 50 cases (72 ± 3 ml/kg/day). Cases with a positive fluid balance received more sodium plus potassium (148 ± 2 versus 133 ± 3 mmol/l, P < 0.001). On average, cases were polyuric (40 ± 5 ml/kg). Mortality was higher in cases (48% versus 10%, P < 0.001), for which hypernatraemia was an independent predictor (odds ratio 4.3, 95% confidence interval 2.5 to 7.2).

Conclusions. Hypernatraemia seems to develop in the ICU because various factors promote renal water loss, which is then corrected with too little water or overcorrected with relatively hypertonic fluids. Therapy should therefore rely on adding electrolyte-free water and/or creating a negative sodium balance. Adjustments in intravenous fluid regimens may prevent hypernatraemia.

Methods. We interrogated the Australian New Zealand Intensive Care Society (ANZICS) Adult Patient Database (APD) for all adult admissions to 57 ICUs from 1 January 2000 to 31 December 2005. We compared the performance of the RIFLE and AKIN criteria for diagnosis and classification of AKI and for robustness of hospital mortality.

Results. We included 120 123 critically ill patients, of which 27.8% had a primary diagnosis of sepsis. We found only small differences (<1%) in the number of patients classified as having some degree of kidney injury using either the AKIN or RIFLE definition or classification systems. AKIN slightly increased the number of patients classified as Stage I injury (category R in RIFLE) (from 16.2 to 18.1%) but decreased the number of patients classified as having Stage II injury (category I in RIFLE) (13.6% versus 10.1%). The area under the ROC curve for hospital mortality was 0.66 for RIFLE and 0.67 for AKIN in all patients and it was 0.65 for both in septic patients.

Conclusion. Compared to the RIFLE criteria, the AKIN criteria do not materially improve the sensitivity, robustness and predictive ability of the definition and classification of AKI in the first 24 h after admission to ICU.

Methods. Between January 1997 and April 2004 all children <1 year of age with a serum creatinine >100 µmol/l at Hannover Medical School were followed up for up to 6 years. One hundred and nineteen children with a serum creatinine >100 µmol/l were identified, 70 infants suffering from ARF and 49 from chronic kidney disease (CKD), stages 3–5.

Results. Renal failure was caused in 49/119 (41%) by congenital and in 70/119 (59%) by acquired diseases. The aetiology of ARF (n = 70) included cardiac (27%), prematurity (27%), septic (10%), hepatic (9%), renal (9%) and other (18%) causes. Twelve infants needed transient dialysis treatment. Renal function recovered in all surviving children. The mortality rate was 37%. Causes of death were unrelated to kidney function. Twenty-one of 49 infants with CKD were dialyzed with a median age of 65 days at the start of dialysis, and 23/49 children received a kidney transplant (RTx). The 5-year patient and graft survival for RTx-children of 95.5% was not different from older children. The 5-year patient survival rate of 26 children with CKD without RTx was 63%. The causes of death were parental refusal of therapy in neonates (n = 4) and life-threatening extra-renal comorbidity (n = 3).

Conclusion. Renal replacement therapy offers good chances of survival in infants without life-threatening comorbidity. Patient survival of infants treated for CKD in the first year of life was comparable to that of older children.

Methods. At a tertiary hospital 110 cardiac surgical patients were randomly allocated to peri-operative infusion of NAC (300 mg/kg over 24 h, N = 30) or placebo (N = 80). We compared the plasma concentrations of creatinine, cystatin C and urea, the plasma creatinine/plasma cystatin C ratio and the estimated GFR at baseline and at 24 and 72 h after commencement of the infusion. We measured urinary creatinine concentration at 24 h.

Results. At baseline, the plasma creatinine/plasma cystatin C ratio did not differ between the NAC and placebo group (0.90 versus 0.92; P = 0.94). There was no significant difference in the plasma creatinine/plasma cystatin C ratio for the NAC and placebo group either during or after NAC infusion at 24 h (1.03 versus 1.00; P = 0.78) and 72 h (0.94 versus 0.89; P = 0.09). Those allocated to NAC showed no difference in urinary creatinine excretion when compared to placebo (P = 0.24).

Conclusions. The results of our study do not demonstrate that NAC artifactually lowers creatinine measured using the Jaffé method. (ClinicalTrials.gov, NCT00332631, NCT00334191)

Aims. In order to evaluate changes in renal blood flow in response to intra-arterial contrast media administration, we aimed to continuously measure renal arterial perfusion by means of renal blood flow velocity (RBFV) during left ventricular and coronary angiography and subsequent coronary intervention in patients with chronic kidney disease (CKD).

Patients and Methods. Ten patients (7 males, 63.4 ± 11.7 years) with serum creatinine (SCr) >1.5 mg/dl participated in the study. The first five patients received low-osmolar iopromide and the others iso-osmolar iodixanol contrast medium. RBFV was measured using a 0.014-inch Doppler guide wire, which was inserted through a separate contralateral femoral sheath via a 5 F Cobra diagnostic catheter into the renal artery. Data were recorded at 500 Hz to allow beat-to-beat analysis of RBFV and pressure. All patients were pre-treated with acetylcysteine and hydration.

Results. Immediately after left ventricular angiography no significant changes in RBFV were detected. Over time, however, following repeated administration of the additional contrast medium into the coronary arteries, RBFV decreased significantly from baseline until the end of the investigation, 28.4 (19.1/42.7) to 22.9 (16.9/30.6) cm/s (median and quartiles; P = 0.005), in the absence of significant changes in systemic arterial blood pressure. In individual patients the reduction in RBVF varied from 3.7% to 39.5%. On average the decline in RBFV was more pronounced in patients receiving iopromide (from 41.6 cm/s to 29.3 cm/s) than in those receiving iodixanol (from 19.3 to 17.8 cm/s; P = 0.008 for the difference of relative decline). However, in the iopromide treated patients, coronary intervention was more frequently performed (5/5 versus 2/5) and the median duration of the procedure tended to be longer [85 (32–150) min versus 38 (27–110) min; P > 0.2].

Conclusions. The administration of non-ionic low-osmolal contrast media has no immediate effect on renal perfusion in patients with CKD. However, during the course of coronary angiography a gradual decline in renal blood flow may occur, the extent of which varies, presumably depending on individual pre-disposition as well as on the amount of the contrast medium.

Methods. Pathologic reports of native kidney biopsies performed for idiopathic proteinuria >3 g/24 h were reviewed. Clinical characteristics and biopsy findings were compared for individuals with serum albumin <30 g/L (Group I), 30 to <35 g/L (Group II) and ≥35 g/L (Group III).

Results. There were 57 patients in Group I, 20 in Group II and 35 in Group III. The proportion of individuals with focal and segmental glomerulosclerosis (FSGS) increased according to group: 26% in Group I, 45% in Group II and 74% in Group III. Of 35 patients in Group III, 34 had FSGS or advanced nephrosclerosis from another cause. Seven of 17 Group III patients with follow-up required dialysis after a mean interval of 6 years. Few of these patients received immunosuppressive therapy.

Conclusions. As serum albumin increases in the nephrotic syndrome, the proportion of patients with FSGS increases. Patients with nephrotic proteinuria and a serum albumin >35 g/L suffer from FSGS, nephrosclerosis and have poor renal survival. When evaluating nephrotic patients, nephrologists should use this knowledge about the spectrum of disease in the clinical decision making of when to perform a biopsy and in providing the patient more precise information regarding risks, benefits and alternatives of the kidney biopsy procedure.

Methods. We did a cross-sectional retrospective analysis of natural history of glomerular filtration rate (estimated— eGFR), albuminuria and proteinuria in 1262 adult patients (585 males, 677 females) from the Fabry Registry.

Results. Twenty-eight percent of males (age 20–79 years) and 13% of females (age 20–82 years) had chronic kidney disease (CKD) with eGFR < 60 ml/min/1.73 m². Overt proteinuria (>300 mg/24 h) was demonstrated in 43 and 26% of males and females with CKD stage 1, respectively, and the proportions were higher with more severe kidney involvement. However, 11% of males and 28% of females with eGFR < 60 ml/min/1.73 m² had proteinuria <300 mg/ 24 h. Of eGFR ≥ 60 ml/min/1.73 m² patients without overt proteinuria (n = 93), 55% of the males and 35% of the females had albuminuria >30 mg/24 h. Systemic blood pressure was ≥130/80 mmHg in 48% and 67% of patients with eGFR ≥ and <60 ml/min/1.73 m², respectively, with no significant differences between males and females. Proteinuria values were significantly correlated with systolic blood pressure in both sexes.

Conclusions. Kidney involvement in Fabry disease is more prevalent and heterogeneous than previously reported. Proteinuria is an early complication, but may not be overt in patients with advanced kidney disease. This analysis, which includes more females than males, confirms that a significant proportion of females suffer moderate to severe kidney involvement in Fabry disease.

Method. Sixty-five IgAN patients, 23 non-IgAN glomerulonephritis patients and 21 normal controls were recruited. Genomic DNA was extracted and the Cosmc gene was PCR amplified and directly sequenced. Peripheral B lymphocytes of IgAN patients and normal controls were isolated, and cultured with RPMI-1640 alone or with lipopolysaccharide (LPS) for 72 h. The Cosmc mRNA expression levels at baseline, after RPMI culture or RPMI + LPS treatment were measured by real-time RT-PCR.

Results. (1) The whole coding frame region of the Cosmc gene was successfully amplified and directly sequenced. Four single nucleotide polymorphisms were detected in two IgAN patients. Two were missense mutations and the others were silent mutations. However, they are different from each other, and unrelated to expression levels; (2) the baseline Cosmc mRNA expression in IgAN patients was significantly lower than normal controls (Ct_COSMC/GAPDH 1.29 ± 0.08 versus 1.20 ± 0.01, 31% of normal controls); (3) the Cosmc mRNA expression level of IgAN patients was remarkably increased after the RPMI culture (1.22 ± 0.12 versus 1.29 ± 0.08, 219% of the baseline level), while not in normal controls and (4) treatment with LPS (culture with RPMI + LPS) could strongly inhibit the expression of Cosmc mRNA (1.25 ± 0.01 versus 1.22 ± 0.12, 61% of the RPMI treatment group).

Conclusion. No common Cosmc gene mutation was detected. Significantly increased Cosmc expression was observed in plasma-free culture, while LPS could significantly inhibit it, which suggested that it might not be genetic disorders but external suppression that causes the low Cosmc mRNA expression in IgAN.

Methods. A retrospective chart review of children with MCNS treated at the VU University Medical Center was performed, identifying 55 patients of whom 4 had LBW. The meta-analysis was performed using Review Manager (The Cochrane Collaboration).

Results. The meta-analysis consisted of 201 patients (25 LBW, 176 normal birth weight). More LBW patients were classified as steroid resistant [odds ratio (OR) 6.97 (95% confidence interval [CI] 2.02–24.04), P = 0.002]. The number of relapses per year of follow-up was significantly higher in the LBW patients with MCNS [weighted mean difference 0.93 (95% CI 0.71–1.15) relapse per year, P < 0.0001]. MCNS patients with LBW were significantly more likely to be treated with cyclosporine [OR 4.4 (95% CI 1.7–11.8), P = 0.003] or cytotoxic agents [OR 4.2 (95% CI 1.8–10.2), P = 0.001] during the course of their disease, and they had a higher chance of developing several complications during the follow-up period, including hypertension.

Conclusions. This meta-analysis provides support for an adverse effect of LBW on the course and prognosis of MCNS in children, which can aid clinicians and parents in assessing the expected clinical course.

Methods. We performed a cross-sectional study of 85 incident patients (51 ± 5 years, 49 males) with type-2 diabetes and 38 age- and sex-matched controls. We further divided patients by the presence of minor (<500 mg/day; n = 40) or severe (≥500 mg/day; n = 45) proteinuria. Clinical and anthropometric data, along with ultrasonographic flow-mediated dilatation (FMD) of the brachial artery and carotid intima-media thicknesses (CIMT), were recorded in each group. Circulating NAMPT/visfatin, adiponectin (normalized to BMI), AHSG/fetuin-A and hsCRP levels were also measured using commercial ELISA.

Results. Plasma NAMPT/visfatin, CIMT, HOMA index and hsCRP levels were all significantly higher in diabetics than in control subjects, and all but CIMT correlated with proteinuria ( = 0.46; P < 0.001, = 0.54; P > 0.05, = 0.32; P = 0.003, = 0.76; P < 0.001, respectively). FMD, adiponectin and AHSG/fetuin-A levels were significantly lower, and negatively correlated with proteinuria ( = –0.54; P < 0.001, = –0.56; P < 0.001, = –0.48; P < 0.001, respectively). In a multivariate regression analysis, the degrees of proteinuria (r² = –0.32, P = 0.04) and plasma levels of NAMPT/visfatin (r² = –0.33, P = 0.006) were independently related to FMD.

Conclusions. The present study suggests that the presence of proteinuria, regardless of the degree of renal function impairment, is an important predictor of endothelial dysfunction in early diabetic nephropathy and that it is associated with altered circulating levels of NAMPT/visfatin and adiponectin.

Methods. This study was designed as a cross-sectional survey study with prospective follow-up. Of the 34 patients identified via searches in registries, 31 males and 2 females who received RRT and ERT (agalsidase beta in 30 patients, agalsidase alpha in 3) were included. Left ventricular mass index (LVMI), interventricular septal thickness at end diastole (IVSD), left ventricular posterior wall thickness (LVPWT) and renal allograft function were assessed at ERT baseline and subsequently at yearly intervals.

Results. The patients in the dialysis and transplant groups had been started on dialysis at age 42.0 and 37.1 years (mean), respectively, and patients in the transplant group received their renal allograft at age 39.8 years (mean). The mean age at the start of ERT was similar, 44.1 and 44.6 years, respectively. The mean RRT follow-up was 61.1 and 110.6 months for dialysis and transplant patients, respectively, whereas the ERT duration was 45.1 and 48.4 months, respectively. Cardiac parameters increased in dialysis patients. In transplant patients, mean LVMI seemed to plateau during agalsidase therapy at a lower level as compared to baseline. Decline in renal allograft function was relatively mild (–1.92 ml/min/year). Agalsidase therapy was well tolerated. Serious ERT-unrelated events occurred more often in the dialysis group.

Conclusions. Kidney transplantation should be the standard of care for Fabry patients progressing towards ESRD. Transplanted Fabry patients on ERT may do better than patients remaining on maintenance dialysis. Larger, controlled studies in Fabry patients with ESRD will have to demonstrate if ERT is able to change the trajectory of cardiac disease and can preserve graft renal function.

Methods. Ten patients were studied in four French pediatric units in order to characterize PHA1 spectrum in infants. Patients were selected by chart review. Genetic, clinical and biochemistry data were collected and analyzed.

Results. Autosomal recessive PHA1 (n = 3) was diagnosed at 6 and 7 days of life in three patients presenting with severe hyperkalaemia and weight loss. After 8 months, 3 and 5 years on follow-up, neurological development and longitudinal growth was normal with high sodium supplementation.

Autosomal dominant PHA1 (n = 4) was revealed at 15, 19, 22 and 30 days of life because of failure to thrive. At 8 months, 3 and 21 years of age, longitudinal growth was normal in three patients who were given salt supplementation; no significant catch-up growth was obtained in the last patient at 20 months of age.

Secondary PHA1 (n = 3) was diagnosed at 11, 26 days and 5 months of life concomitantly with acute pyelonephritis in three children with either renal hypoplasia, urinary duplication or bilateral megaureter. The outcome was favourable and salt supplementation was discontinued after 3, 11 and 13 months.

Conclusions. PHA1 should be suspected in case of severe hyperkalemia and weight loss in infants and need careful management. Pathogenesis of secondary PHA1 is still challenging and further studies are mandatory to highlight the link between infection, developing urinary tract and pseudohypoaldosteronism.

Methods. We used neutrophils from three groups of haemodialysis (HD) patients before dialysis (Groups A, B and C) and also from age- and sex-matched healthy individuals to determine pHi, phagocytosis and expression of CD11b, CD18, CD14 and toll-like receptors (TLR)-2 and TLR-4. The patients were categorized based on three consecutive monthly pre-dialysis plasma bicarbonate concentrations(P_HCO3) and pH values; Groups A, B and C had a constant pre-dialysis P_HCO3 of ≤21, 21–26 and ≥26 mmol/L (mEq/L), respectively. We also studied the effects induced by the correction of metabolic acidosis and monoclonal antibodies (mAbs) against CD11b/CD18 on neutrophils in Group A. Furthermore, we investigated the effect of intracellular acidification on uraemic neutrophils ex vivo.

Results. We observed that the neutrophils in Group A exhibited significantly increased phagocytosis and expression of CD11b/CD18 compared with those in Groups B and C. Additionally, our ex vivo studies demonstrated that the mAbs against CD11b/CD18 partially blocked the enhancement of neutrophil phagocytosis in Group A. Moreover, the pHi of uraemic neutrophils is inversely correlated with phagocytosis and expression of CD11b/CD18.

Conclusions. HD patients with a low P_HCO3 exhibited low neutrophil pHi that in turn increased the expression of CD11b/CD18 compared with neutrophils with a normal or high pHi. This increased expression of CD11b/CD18 on the uraemic neutrophils may contribute to the pHi-mediated phagocytosis.

Methods. We measured 1–84 PTH (‘biointact’ or ‘whole’ PTH) and total PTH (‘intact’ PTH) in a national cohort of 515 incident dialysis patients from banked frozen EDTA plasma (median follow-up, 35 months) and examined the accuracy of estimating 1–84 PTH from total PTH and the associations of these levels with patient characteristics and mortality.

Results. The 1–84 PTH and total PTH levels were closely correlated. Higher 1–84 PTH was associated with African-American race and higher serum phosphate and lower calcium levels. The percentage of total PTH represented by 1–84 PTH was, on average, 53%, but with a wide range (25–89%). Calculating 1–84 PTH from total PTH using a proposed standard conversion factor (54%) led to misclassification of 8% of the population compared with measured 1–84 PTH. In a multivariate Cox proportional hazards model for all-cause mortality, a 1–84 PTH value >160 pg/ml was associated with increased risk of mortality (HR = 1.62, 95% CI, 1.03–2.54) compared to a level of 80–160 pg/ml. Elevated total PTH, 7–84 PTH and the 1–84 PTH/7–84 PTH ratio were not significantly associated with mortality.

Conclusions. The 1–84 PTH and total PTH are highly correlated. Elevated 1–84 PTH was significantly associated with increased mortality, whereas total PTH did not reach statistical significance. Thus, although in other respect they are similar, there may be utility in measuring 1–84 PTH for its associations with mortality.

Methods. Surveillance for nasal MRSA carriage and infection among dialysis patients, healthcare workers (HCWs) and their family members in a dialysis centre was prospectively undertaken during three time periods within 1 year. Molecular typing was used to determine epidemiological relationship.

Results. Among 1687 samples collected, MRSA colonization rates were 2.41% (2/83) for peritoneal dialysis patients and 2.36% (12/509) for haemodialysis patients. Five (5/14) subjects subsequently had MRSA infection. The clinical MRSA isolates had the same molecular type as the colonized strains of the same person, indicating MRSA colonization preceded clinical infection. Significantly higher MRSA nasal carriage rates were observed among family members of HCWs than family members of dialysis patients (P = 0.0024). Only three major clones were observed. Pulmonary diseases (OR: 4.873, 95% CI: 1.668–14.235), recent admission to a hospital (OR: 2.797, 95% CI: 1.291–6.059) and recent antibiotics usage (OR: 2.319, 95% CI: 1.053–5.104) were also significantly associated with MRSA carriage.

Conclusion. Transmission of MRSA among dialysis patients, HCWs and their family members in a dialysis unit could be inferred. Monitoring and eradication of MRSA from patients, HCWs and their family members should be considered to prevent continuous spread between healthcare facilities and the community.

Methods. We collected from Medline, Web of Science, the Cochrane Library and major nephrology journals, all relevant references (January 1990–March 2007). We selected RCT comparing an ALS to a standard heparin lock in CRB prevention. We extracted data concerning study quality, patient characteristics and CRB incidence. The relative risk (RR) of CRB was calculated as Ln (CRB incidence control/CRB incidence experimental) using both a fixed- and a random-effects model.

Results. Eight studies were included, involving 829 patients, 882 catheters and 90 191 catheter-days. The use of an ALS significantly decreased the risk of CRB (RR 0.32; 95% CI 0.10–0.42). Borderline heterogeneity was observed in the fixed-effects model (Q = 14.42; P = 0.071). Despite the under-representation of small negative studies, the high number of additional trials necessary to reverse the final effect strengthens the confidence in the overall results. Subgroup analyses stratified by the presence of diabetes, duration of follow-up, biochemical markers, proportion of tunnelled cuffed catheters, intranasal mupirocin use and citrate use in the ALS did not show significant differences, except a higher efficacy of gentamicin-containing lock solutions (P = 0.003).

Conclusions. The use of ALS reduces by about a factor 3 the risk of CRB in haemodialysis patients. The achieved absolute incidence is similar to the best-published figures (presumably related to stricter hygienic measures). The limited follow-up of the studies does not exclude the onset of adverse events or bacterial resistance with longer use of ALS.

Methods. Thirty haemodialysis (HD), 30 peritoneal dialysis (PD) and 30 chronic kidney disease (CKD) patients were enrolled in our study. For all patients, serum C-reactive protein (CRP) and ferritin levels were determined. In addition, the expression level of 234 inflammatory responses and oxidative stress pathway genes was measured, using oligonucleotide microarray chips (HG-U133A, Affymetrix), in peripheral blood mononuclear cells of 24 randomly selected patients (8 HD, 8 PD and 8 CKD).

Results. HD patients demonstrated higher CRP and ferritin levels compared to PD and CKD patients (P < 0.001). Statistical analysis identified 10 genes able to discriminate CKD from HD and PD patients (FDR = 5%, P < 0.001) and significantly correlated to CRP levels. All together, these genes were able to predict inflammation with an accuracy of 87% (P < 0.001). Among the selected genes there were those encoding for key regulators of inflammation and oxidative stress (e.g. RELA, GSS). Interestingly, only three inflammatory genes (MIF, IL8RB and CXCL12) were still significantly associated with inflammation when included in a multivariate analysis. RT–PCR for RELA, MIF, CXCL12 and western blots for IL8RB and GSS, using 66 patients, validated the microarray results.

Conclusions. This study may help to better understand the physiopathology of the systemic inflammatory state in CKD and dialysis patients and to identify new target genes potentially useful for future bio-molecular studies and therapeutic approaches.

Methods. We constructed an incident cohort including patients whose day 91 after dialysis initiation fell between 1 January and 31 December 2002. Haemoglobin concentration, erythropoiesis-stimulating agent dose, comorbid condition and hospitalization data were obtained from Medicare claims. Patients were classified by 0, 1, 2 or 3 months with haemoglobin concentration below the K/DOQI target (11 g/dL). Using an inverse probability weighted marginal structural model to adjust for time-varying factors associated with haemoglobin concentration, we determined the association between number of months below target and subsequent risk for hospitalization and mortality.

Results. The final cohort included 54 328 patients who met criteria. Those with more months below haemoglobin target were less likely to have received intravenous iron. More months below target were associated with increased risk of hospitalization (RR 1.70, 95% CI 1.63–1.76) and mortality (RR 2.48, 95% CI 2.28–2.69).

Conclusions. Future interventions should focus on modifiable factors associated with greater time below target haemoglobin concentrations to determine whether altering the time below target can alter the risk of hospitalizations or mortality.

Objectives. The aims of this study were (1) to identify risk factors (comorbidity and variables specific to haemodialysis) associated with death in the first year following the start of haemodialysis and (2) to design and validate a prognostic model to quantify the probability of death for each patient.

Methods. An analysis was carried out on all patients starting haemodialysis treatment in Catalonia during the period 1997–2003 (n = 5738). The data source was the Renal Registry of Catalonia, a mandatory population registry. Patients were randomly divided into two samples: 60% (n = 3455) of the total were used to develop the prognostic model and the remaining 40% (n = 2283) to validate the model. Logistic regression analysis was used to construct the model.

Results. One-year mortality in the total study population was 16.5%. The predictive model included the following variables: age, sex, primary renal disease, grade of functional autonomy, chronic obstructive pulmonary disease, malignant processes, chronic liver disease, cardiovascular disease, initial vascular access and malnutrition. The analyses showed adequate calibration for both the sample to develop the model and the validation sample (Hosmer-Lemeshow statistic 0.97 and P = 0.49, respectively) as well as adequate discrimination (ROC curve 0.78 in both cases).

Conclusions. Risk factors implicated in mortality at one year following the start of haemodialysis have been determined and a prognostic model designed. The validated, easy-to-apply model quantifies individual patient risk attributable to various factors, some of them amenable to correction by directed interventions.

Methods. Twenty chronic HD patients, 20 predialytic uraemic patients and 20 healthy subjects were included in the study. Serum thiobarbituric acid reactive substances (TBARS), protein carbonyl content (PCO) and nitrite/nitrate levels were determined as oxidative stress markers. Serum vitamin E, plasma sulfhydryl (P-SH), erythrocyte glutathione (GSH), superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) activities were measured as antioxidants. CIMT was assessed by carotid artery ultrasonography.

Results. Both chronic HD and predialytic uraemic patients had enhanced oxidative stress indicated by higher levels of nitrite/nitrate, TBARS and PCO, and lower levels of P-SH, SOD, CAT and GPx compared to controls. HD patients had significantly higher CIMT and nitrite/nitrate while significantly lower P-SH,vitamin E, SOD, CAT and GPx compared to predialytic uraemic patients. There was a significant positive correlation between CIMT and TBARS (r = 0.38, P = 0.003) and nitrite/nitrate levels (r = 0.41, P = 0.001), while there was a significant negative correlation between CIMT and SOD (r = –0.35, P = 0.01), CAT (r = –0.65, P < 0.001) and P-SH levels (r = –0.50, P < 0.001). A linear regression analysis showed that TBARS were still significantly and positively correlated with CIMT (P = 0.001), while CAT and P-SH were significantly and negatively correlated with CIMT (P = 0.002 and P = 0.048, respectively).

Conclusions. HD exacerbates oxidative stress and disturbances in antioxidant enzymes in uraemic patients. We propose that serum TBARS and nitrite/nitrate can be used as positive determinants, while erythrocyte SOD, CAT and P-SH may be used as negative determinants of atherosclerosis assessed by CIMT in uraemic and HD patients.

Methods. Total removal and instantaneous clearances of urea, phosphorus, β₂-microglobulin, leptin, angiogenin, complement factor D and immunoglobulin light chain were determined in randomized cross-over studies. Total solute removal was assessed from the pre- to post-dialysis change in plasma concentration and the total amount of solute recovered in the dialysate. Trapping of solute at the membrane was determined as the difference between solute lost from plasma water and solute recovered in the dialysate.

Results. Total removal of urea and phosphorus was independent of the membrane composition and structure. Large molecule removal differed significantly between the two membranes, particularly for β₂-microglobulin. The importance of trapping at the membrane as a mechanism of β₂-microglobulin removal also differed significantly between the two membranes, with trapping being less important for the membrane with the greatest β₂-microglobulin removal. As molecular size increased, the contribution of trapping at the membrane to solute removal increased and the difference between the two membranes decreased.

Conclusions. High-flux membranes fabricated from nominally similar polymers may differ significantly in their ability to remove low molecular weight protein uraemic toxins.

We selected a cohort of caregivers that are actively involved with the care of their partners’ dialysis. Quality of Life (QoL) assessed by SF-36 questionnaires showed the patients and carers had impairment of QoL at the start of dialysis. As expected, the baseline QoL Physical Component Scores highly correlated with co-morbidity and assessment of functional capacity. Scores of all QoL domains improved after 1 year and this reached statistical significance for social functioning for both patients and carers. When we compared carers of highly dependent patients (required to perform daily dialysis) with carers of less dependent patients, we noted that the former had a statistically significant worsening of their mental health but other parameters were not different.

We have shown that despite increasing the burden for caregivers, with careful selection, education and support, we did not adversely impact on the QoL of carers whilst there was some evidence of improvement, especially in social functioning. This gives reassurance that establishing dependent patients on PD is compatible with a holistic approach to the patients and their families.

Methods. Between November 2005 and April 2006, a random sample was taken of British and Irish residents in southeastern Spain (n = 1700) and stratified by the respondent's nationality. Attitude was evaluated using a validated questionnaire that was completed anonymously and self-administered.

Results. The questionnaire completion rate was 90% (n = 1533). Ninety percent (n = 1384) are in favour of related living kidney donation, 9% (n = 138) are against and the remaining 1% (n = 11) are unsure. The following variables are related to attitude towards living kidney donation: (1) attitude towards cadaveric organ donation (P < 0.001); (2) having previous experience with the donation and transplantation process (P = 0.001); (3) participation in social help activities (P = 0.010); (4) having spoken about the matter within the family unit (P = 0.036); (5) the attitude of a respondent's partner towards the matter (P = 0.001); (6) knowing that one's own religion is in favour of this type of therapy (P = 0.002); (7) evaluation of the risks involved in this kind of donation (P < 0.001) and (8) concern about ‘mutilation’ after donation (P < 0.001). In the multivariate analysis, two variables are significantly related to this attitude: a negative attitude towards cadaveric donation (odds ratio = 0.309) and knowing that one's religion is in favour (OR = 1.745).

Conclusions. The attitude of British and Irish citizens who are resident in southeastern Spain is very favourable and their attitude is very closely related to attitude towards cadaveric donation, family attitude and the attitude of their religion. The patients on the waiting list who are of British or Irish origin would be an ideal group to whom living kidney donation could be offered.

Methods. In this study, 132 incident patients undergoing tacrolimus and mycophenolate mofetil-based renal transplantation were studied for the prevalence of, and risk factors for, anaemia and CHF in the early period post transplantation.

Results. Anaemia occurred in 94.5% and 53.1% of patients at 1 week and 12 months, respectively, and was associated with allograft dysfunction, hypoalbuminaemia, higher mycophenolic acid (MPA) levels, bacterial infection and hypoalbuminaemia. The association with hypoalbuminaemia may reflect the presence of chronic inflammation post-transplantation. Of patients displaying haemoglobin <11 g/dl, 41.1% and 29.4% were treated with erythropoiesis stimulating agents (ESAs) at 1 and 12 months respectively. CHF developed in 26 patients beyond 1 month post-transplantation, with echocardiographic left ventricular systolic function preserved in all but one. CHF was associated with anaemia and lower haemoglobin, allograft dysfunction, duration of dialysis and left ventricular hypertrophy on echocardiography prior to transplantation, suggesting the aetiology of CHF may involve the interplay of diastolic cardiac dysfunction, pre-load mismatch and after-load mismatch.

Conclusions. Modification of risk factors may improve anaemia management post transplantation. Reducing the prevalence of anaemia may in turn reduce the incidence of CHF—these observations support the need for clinical trials to determine how anaemia management may impact CHF incidence.

Aims. The aim of this study was to evaluate the role of histomorphology and C4d immunostaining in indicated renal allograft biopsies with a clinical follow-up for a minimum duration of 1 year.

Material and methods. Histological analysis and C4d immunostaining were performed on 132 needle core biopsies and 2 nephrectomy specimens from 107 patients from July 2004 to June 2005.

Results. Histological analysis revealed 59 cases of acute rejection, 10 biopsies of acute tubular necrosis, 41 cases of chronic allograft nephropathy (CAN), either alone or in combination with other diseases, and 18 biopsies of normal morphology. There were four cases of BK nephropathy (BK N) and eight cases had miscellaneous diagnoses. C4d immunostaining was performed on 126 biopsies. Overall, the prevalence of C4d positivity was 45% (57 of 126). Fifty-five percent (28 of 51) of the cases of acute rejection showed C4d positivity including 81% of presumptive antibody-mediated rejection (P-AbAR), 20% acute cellular rejection and 58% acute cellular rejection + P-AbAR. Overall C4d positivity was 37% in chronic allograft nephropathy. Acute tubular necrosis and borderline rejection showed 25 and 50% C4d positivity, respectively. Amongst various histological features, capillary margination of polymorphs and dilatation of peritubular capillaries (PTC-D) showed significant association with C4d positivity (P < 0.005). In cases of CAN, transplant glomerulopathy had significant association with C4d positivity. C4d-positive cases had a higher mean value of serum creatinine at the time of biopsies.

Conclusion. It is concluded that C4d staining is a useful adjunct marker of the humoral limb of rejection, both in early and late post-transplant periods.

Methods. We conducted an open cohort study of 2041 first renal allograft recipients, transplanted at the Medical University of Vienna between 1990 and 2003. Serum potassium levels were compared over an up to 10 years of observation period between subjects with versus without ACEI/ARB therapy using a mixed effects general linear model. The analysis was adjusted for several covariables known to influence serum potassium such as the use of diuretics, beta blockers, calcineurin inhibitor (CNI) based immunosuppression, estimated GFR, time since renal transplantation, diabetes, years on dialysis and recipient age.

Results. The overall adjusted estimated serum potassium difference between recipients with versus without ACEI/ARB therapy was 0.08 mmol/l (P < 0.001). The use of diuretics was associated with a 0.11 mmol/l (P < 0.001) lower potassium concentration whereas each GFR decrease by 10 ml/min led to an increase of 0.04 mmol/l (P < 0.001). CNI intake increased serum potassium by 0.06 mmol/l (P = 0.002). Furthermore, serum potassium increased by 0.17 mmol/l within the first decade after transplantation (P < 0.001) while holding the other covariables constant. No effect modification between ACEI/ARB and time since transplantation was observed. Nineteen subjects (2.4%) discontinued the ACEI/ARB therapy due to hyperkalaemia.

Conclusions. In summary, relevant hyperkalaemia associated with ACEI/ARB therapy is negligible in renal transplant recipients during long-term follow-up. The hyperkalaemic effect of ACEI/ARB is balanced by the use of diuretics.

Methods. In this retrospective study, we analysed patient records of all children under age 2 treated with continuous peritoneal dialysis (CPD) between 1995 and 2000 in Finland. Diagnoses leading to renal failure in these 23 children were congenital nephrotic syndrome of the Finnish type (13), polycystic kidney disease (4), a urethral valve (3), renal insufficiency due to neonatal asphyxia (2) and Prune-Belly syndrome (1). Of these 23, 17 (74%) were anuric.

Results. The mean age at the onset of PD was 0.4 years and the mean time on dialysis 1.4 years. Hernias were diagnosed in 57%. The peritonitis rate was 1:14.5 patient-months, and 30% were peritonitis-free. Hypertension was common, and 70% had at least one period on antihypertensive medication. None of the patients had pulmonary oedema or dialysis-related seizures. The mean height standard deviation score (hSDS) at the start of PD (n = 16) was –2.0 and after 9 months –1.6. Catch-up growth was documented in 64% of the patients during dialysis. Hospitalization time was 124 days/patient-year. Two patients (9%) died.

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