A. Kark

Maintenance of elevated versus physiological iron indices in non-anaemic patients with chronic kidney disease: a randomized controlled trial

BACKGROUND An optimal haemoglobin (Hb) response to erythropoietin requires elevated iron indices in dialysis patients; however, it is unknown if the same applies in chronic kidney disease (CKD). METHODS One hundred patients [CKD Stages 3-5, Hb >or= 110 g/L, iron replete, erythropoietin-stimulating agent (ESA)-naive, 47% diabetic, median age 69.5 years] were block-randomized in an open-label study to receive up to 200 mg intravenous iron sucrose (Group A, n = 52) bimonthly or oral iron sulphate (Group B) to maintain raised and normal iron indices (respectively) over 12 months. The primary endpoint was the change in Hb concentration at 12 months or at termination after at least 6 months of treatment. RESULTS Eighty-five patients reached the primary endpoint (43, Group A; 42, Group B). Initial Hb was 119 +/- 7 vs 116 +/- 12 g/L (mean +/- standard deviation); ferritin 122 (71-176), median (inter-quartile range), vs 90 microg/L (58-150); transferrin saturation (TSat) 22 (18-26) vs 21% (15-24); and creatinine 240 (195-313) vs 230 micromol/L (184-352). Ferritin and TSat differed by month 2 [157 (103-220) vs 96 microg/L (73-162), P = 0.003] and month 6 [25 (20-31) vs 21% (17-27), P = 0.02], respectively. At study end, Hb did not differ between groups (121 +/- 10 vs 117 +/- 13 g/L). Ferritin was 362 (310-458) vs 125 microg/L (84-190), P < 0.001; TSat 30 (23-34) vs 21% (18-24), P < 0.001; and creatinine 229 (188-326) vs 272 micromol/L (195-413), P = NS. For patients (Groups A and B, n = 27 in each group) whose creatinine regression slope increased (indicating worsening function), the fall in Hb over 12 months also did not differ between groups despite adequate separation in iron indices. Serious adverse events overall did not differ between groups. CONCLUSIONS Elevated iron indices did not increase Hb synthesis in ESA-naive, iron replete, pre-dialysis patients with Hb >110 g/L.

Development and validation of a dietary screening tool for high sodium consumption in Australian renal patients.

OBJECTIVE The study objective was to develop and evaluate the feasibility and validity of a self-administered Scored Sodium Questionnaire (SSQ) for use in the routine clinical care of Australian chronic kidney disease (CKD) patients. DESIGN AND METHODS The study took place in community-based outreach clinics using a multidisciplinary model of care. Assessment of sources of dietary sodium intake in the target population used comprehensive diet history interviews (Phase 1) to inform development of a 10-item food frequency questionnaire that was scored and validated using 24-hour urinary sodium and 2 alternative dietary intake methods (Phase 2). Subjects were adults with CKD Stages 3 to 5 (Phase 1 n = 30; Phase 2 n = 47). INTERVENTION On a single day, participants (n = 47) completed the SSQ, feasibility survey, 24-hour urine collection, and 24-hour food record. A diet history interview was also conducted to confirm sodium intake on the day of data collection reflected habitual intake. MAIN OUTCOME MEASURE Validity of the SSQ score was confirmed by correlation with 24-hour urine sodium. Validity of a cutpoint on the SSQ score to correctly identify high- versus low-sodium consumers was confirmed by receiver operating characteristic curve analysis: area under the curve, sensitivity, and specificity. RESULTS Total SSQ score correlated significantly with 24-hour urine sodium (r = 0.371; P = .031). Correlation between 24-hour food record and diet history sodium confirmed consumption on the data collection day reflected habitual intake (r = 0.701; P ≤ .001). A cutpoint of 65 or greater on the SSQ score was confirmed as valid to identify high-sodium consumers: area under the curve 0.713, sensitivity 61%, and specificity 82%. CONCLUSION The SSQ is feasible and valid to assess habitual sodium intake in the Australian CKD population and to identify high-sodium consumers for referral to individualized counseling on a low-sodium diet.

Pharmacokinetics of Intraperitoneal Cefalothin and Cefazolin in Patients Being Treated for Peritoneal Dialysis-Associated Peritonitis.

♦ Background: The standard treatment of peritoneal dialysis (PD)-associated peritonitis (PD-peritonitis) is intraperitoneal (IP) administration of antibiotics. Only limited data on the pharmacokinetics and appropriateness of contemporary dose recommendations of IP cefalothin and cefazolin exist. The aim of this study was to describe the pharmacokinetics of IP cefalothin and cefazolin in patients treated for PD-peritonitis. ♦ Methods: As per international guidelines, IP cefalothin or cefazolin 15 mg/kg once daily was dosed with gentamicin in a 6-hour dwell to patients with PD-peritonitis during routine care. Serial plasma and PD effluent samples were collected over the first 24 hours of therapy. Antibiotic concentrations were quantified using a validated chromatographic method with pharmacokinetic analysis performed using a non-compartmental approach. ♦ Results: Nineteen patients were included (cefalothin n = 8, cefazolin n = 11). The median bioavailability for both antibiotics exceeded 92%, but other pharmacokinetic parameters varied markedly between antibiotics. Both antibiotics achieved high PD effluent concentrations throughout the antibiotic dwell. Cefazolin had a smaller volume of distribution compared with cefalothin (14 vs 40 L, p = 0.003). The median trough total plasma antibiotic concentration for cefazolin and cefalothin during the dwell differed (plasma 56 vs 13 mg/L, p < 0.0001) despite a similar concentration in PD effluent (37 vs 38 mg/L, p = 0.58). Lower antibiotic concentrations were noted during PD dwells not containing antibiotic, particularly cefalothin, which was frequently undetectable in plasma and PD effluent. The median duration that the unbound antibiotic concentration was above the minimum inhibitory concentration (MIC) was approximately 13% (plasma) and 25% (IP) for cefalothin, and 100% (plasma and IP) for cefazolin, of the dosing interval. ♦ Conclusions: When IP cefalothin or cefazolin is allowed to dwell for 6 hours, sufficient PD effluent concentrations are present for common pathogens during this time. However, with once-daily IP dosing, in contrast to cefazolin, there is a risk of subtherapeutic plasma and PD effluent cefalothin concentrations, so more frequent dosing may be required.

Sustained remission of systemic lupus erythematosus related calciphylaxis

Calciphylaxis continues to present a clinical challenge for patient management. As in this case, it can be associated with connective tissue disease (CTD) such as systemic lupus erythematosus (SLE). Unlike previous reported cases, long-term remission has been attained. This provides some insight into methods of therapy as well as potential pathogenic models for this disease.

The Prevalence and Characteristics of Acute Interstitial Nephritis (Ain) and Pyelonephritis in Patients with Chronic Kidney Disease (Ckd)

Aim: To investigatenongenomic effects of aldosteroneon renal protein expressions of sodium hydrogen exchanger 1 and 3 (NHE1and3), andproteinkinaseCbeta 1 and2 (PKCβ 1 and2) Introduction: Wehave previously demonstrated that aldosterone rapidly elevates epidermal growth factor receptor (EGFR) phosphorylation and increases extracellular signal-related kinase1and2(ERK1⁄2)inratkidney.ERK1⁄2inducedbyaldosterone activates NHE (1 and 3) in renal tubular cells. In vitro studies showed that aldosterone nongenomically stimulates PKCβ. PKCβ1alsomediatedstimulationofNHEactivity.Therearenoreports ofproteinexpressionsofNHE(1and3)andPKCβ (1and2) simultaneously in ratkidney regarding these circumstances. Methods: Male Wistar rats were intraperitoneally injected with normal saline solution or aldosterone (150mg/kg BW). After 30minutes, abundances and localizations of NHE (1 and 3) and PKCβ (1 and 2) proteins were determined by Western blot analysis and immunohistochemistry, respectively. Results: ByWestern blot analysis, aldosterone increased renal protein abundances of NHE1 andNHE3 to be 152%and 134%, respectively (P< 0.05). Aldosterone significantly enhanced protein abundances of PKCβ1 by 30%, whereas PKCβ2 protein trended to decline. Aldosterone increasedmore protein expressions of NHE1 and NHE3 in the medulla than cortex. Protein expression PKCβ1 was enhanced in the glomeruli, renal vasculatures and thin limb of Henles loop by aldosterone. However, PKCβ2 was declined in the medulla. Conclusion: This in vivo study is the first to demonstrate simultaneously that aldosterone rapidly elevates PKCβ1 and NHE (1 and 3) protein abundances in rat kidney. The stimulation of NHE protein expressions by aldosterone, per se, may occur through PKCβ1 activation. 002 KEY ROLE OFAPOPTOSIS INHIBITOR OF MACROPHAGE IN PHLOGOGENIC ACTION OF GLOMERULAR NEPHRITOGENIC IGA IN IGA NEPHROPATHY TAKAHATA A, KITADA K, NOGI C, ARAI S, MAKITA Y, SUZUKI H, NAKATA J, HORIKOSHI S, MIYAZAKI T, SUZUKI Y Division of Nephrology, Department of Internal Medicine Juntendo University School of Medicine, Bunkyo-ku, Japan, Laboratory of Molecular Biomedicine for Pathogenesis, Center for Disease Biology and Integrative Medicine, Faculty of Medicine, The University of Tokyo, Bunkyo-ku, Japan

The Association Between Cancer and Acute Tubular Necrosis (Atn) in Patients with Chronic Kidney Disease (Ckd)

Aim: To investigatenongenomic effects of aldosteroneon renal protein expressions of sodium hydrogen exchanger 1 and 3 (NHE1and3), andproteinkinaseCbeta 1 and2 (PKCβ 1 and2) Introduction: Wehave previously demonstrated that aldosterone rapidly elevates epidermal growth factor receptor (EGFR) phosphorylation and increases extracellular signal-related kinase1and2(ERK1⁄2)inratkidney.ERK1⁄2inducedbyaldosterone activates NHE (1 and 3) in renal tubular cells. In vitro studies showed that aldosterone nongenomically stimulates PKCβ. PKCβ1alsomediatedstimulationofNHEactivity.Therearenoreports ofproteinexpressionsofNHE(1and3)andPKCβ (1and2) simultaneously in ratkidney regarding these circumstances. Methods: Male Wistar rats were intraperitoneally injected with normal saline solution or aldosterone (150mg/kg BW). After 30minutes, abundances and localizations of NHE (1 and 3) and PKCβ (1 and 2) proteins were determined by Western blot analysis and immunohistochemistry, respectively. Results: ByWestern blot analysis, aldosterone increased renal protein abundances of NHE1 andNHE3 to be 152%and 134%, respectively (P< 0.05). Aldosterone significantly enhanced protein abundances of PKCβ1 by 30%, whereas PKCβ2 protein trended to decline. Aldosterone increasedmore protein expressions of NHE1 and NHE3 in the medulla than cortex. Protein expression PKCβ1 was enhanced in the glomeruli, renal vasculatures and thin limb of Henles loop by aldosterone. However, PKCβ2 was declined in the medulla. Conclusion: This in vivo study is the first to demonstrate simultaneously that aldosterone rapidly elevates PKCβ1 and NHE (1 and 3) protein abundances in rat kidney. The stimulation of NHE protein expressions by aldosterone, per se, may occur through PKCβ1 activation. 002 KEY ROLE OFAPOPTOSIS INHIBITOR OF MACROPHAGE IN PHLOGOGENIC ACTION OF GLOMERULAR NEPHRITOGENIC IGA IN IGA NEPHROPATHY TAKAHATA A, KITADA K, NOGI C, ARAI S, MAKITA Y, SUZUKI H, NAKATA J, HORIKOSHI S, MIYAZAKI T, SUZUKI Y Division of Nephrology, Department of Internal Medicine Juntendo University School of Medicine, Bunkyo-ku, Japan, Laboratory of Molecular Biomedicine for Pathogenesis, Center for Disease Biology and Integrative Medicine, Faculty of Medicine, The University of Tokyo, Bunkyo-ku, Japan

Heterogeneity of chronic kidney disease (CKD) by age in an Australian metropolitan renal service.

Aim: To serially assess the longitudinal effect of an episode of peritonitis on peritoneal membrane function and clinical outcomes. Background: Peritoneal dialysis (PD) peritonitis carries a significant risk of peritoneal membrane injury. Methods: We identified 27 patients with PD peritonitis over a 4 year period at a single tertiary hospital. Peritoneal adequacy tests at an “early” (1–3 months), “intermediate” (6 ± 2 months) and a “late” (12 ± 2 months) time period after the episode were obtained and the results compared with a pre-peritonitis baseline. The effect of time on serum albumin, creatinine clearance, Kt/V and fluid volume removal was analysed using a linear mixed effects regression model. Results: At one year 15/27 (55%) patients were no longer on PD (9 on haemodialysis, 1 transplanted). 5/27 (18%) were deceased. Total fluid volume removal significantly decreased over time with an aggregated mean reduction of 523 mls/ day between the baseline and 12 month test (1624 ml ± 139 vs. 1101 ml ± 160; p = 0.02). This decrease was due to an equivalent loss of both ultrafiltration and residual urine output. The decline in these individual parameters was not statistically significant. There was no significant change in Kt/V, creatinine clearance or albumin indicating preserved solute transport in those patients with sustained technique survival post peritonitis. Conclusions: PD peritonitis is associated with high a rate of mortality and treatment failure. Overall fluid removal capabilities are the most significantly affected at one year post peritonitis, driven by both ultrafiltration reduction and loss of residual diuresis.

Acute kidney injury (AKI) associated with chronic kidney disease (CKD) in the renal practices of the Royal Brisbane and Women's Hospital (RBWH)through the CKD.QLD registry.

Aim: To serially assess the longitudinal effect of an episode of peritonitis on peritoneal membrane function and clinical outcomes. Background: Peritoneal dialysis (PD) peritonitis carries a significant risk of peritoneal membrane injury. Methods: We identified 27 patients with PD peritonitis over a 4 year period at a single tertiary hospital. Peritoneal adequacy tests at an “early” (1–3 months), “intermediate” (6 ± 2 months) and a “late” (12 ± 2 months) time period after the episode were obtained and the results compared with a pre-peritonitis baseline. The effect of time on serum albumin, creatinine clearance, Kt/V and fluid volume removal was analysed using a linear mixed effects regression model. Results: At one year 15/27 (55%) patients were no longer on PD (9 on haemodialysis, 1 transplanted). 5/27 (18%) were deceased. Total fluid volume removal significantly decreased over time with an aggregated mean reduction of 523 mls/ day between the baseline and 12 month test (1624 ml ± 139 vs. 1101 ml ± 160; p = 0.02). This decrease was due to an equivalent loss of both ultrafiltration and residual urine output. The decline in these individual parameters was not statistically significant. There was no significant change in Kt/V, creatinine clearance or albumin indicating preserved solute transport in those patients with sustained technique survival post peritonitis. Conclusions: PD peritonitis is associated with high a rate of mortality and treatment failure. Overall fluid removal capabilities are the most significantly affected at one year post peritonitis, driven by both ultrafiltration reduction and loss of residual diuresis.

The Heterozygous P.R76W Hnf4A Variant Is Associated with Atypical Autosomal Dominant De Toni-Fanconi-Debre Syndrome and Can Be Diagnosed Utilising Diagnostic Clinical Exomic Analysis

021 CELL BASED THERAPY IN COMBINATION WITH SERELAXIN IS CRITICAL FOR PRESERVATION OF VASCULAR INTEGRITY VIA PROMOTION OF ANGIOGENESIS AND ANASTOMOSIS B HUUSKES1, A PINTO2, C SAMUEL3, S RICARDO1 1Department of Anatomy and Developmental Biology, Monash University, Clayton, Victoria; 2Australian Regenerative Medicine Institute, Monash University, Clayton, Victoria; 3Department of Pharmacology, Monash University, Clayton, Victoria