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The use of antibiotic lock solutions as prophylaxis for catheter-associated blood stream infection (CRBSI) has been shown to be effective in previous randomized controlled trials. However, the cost-effectiveness of this approach had not been studied. In 2012, the routine gentamicin-heparin lock solution used in Auckland City Hospital was withdrawn from the market, leading to a change to heparin-only lock. This was then replaced with gentamicin-citrate lock in 2014. This situation allowed review of the CRBSI rate and financial impact of different catheter lock solutions. A retrospective audit was performed from 1 January 2011 to 31 December 2015 to investigate the rate of culture-proven CRBSI in patients with tunneled cuffed dialysis catheters. There were 89 cases of CRBSI involving 64 patients in the 5-year period. In comparison with the heparin-only lock, both gentamicin-heparin and gentamicin-citrate locks had a significantly lower rate of bacteremia, with rate ratios of 0.46 (confidence interval 0.30-0.72) and 0.11 (confidence interval 0.05-0.22), respectively. The inpatient costs as a consequence of the CRBSI were NZ$27 792 per 1000 catheter days for heparin-only lock, NZ$10 608.56 per 1000 catheter days for gentamicin-heparin lock, and NZ$ 1898.45 per 1000 catheter days for gentamicin-citrate lock. The lack of antibiotic lock solutions led to an increase in bacteremia rates and higher financial cost for inpatient management of bacteremia. Our findings highlight the importance of consistent supply of pharmaceuticals.

Background. Membranous nephropathy (MN) can be associated with malignancy. However, the relative risk for malignancy remains unclear. It has been reported that higher numbers of inflammatory cells seen in the glomeruli at biopsy correlate with the occurrence of malignancy in patients with MN and might be used to direct screening. Methods. We examined the occurrence of malignancy in 201 MN patients in Auckland, New Zealand. We also examined the pathology of renal biopsies from 17 MN patients with malignancies and compared the number of inflammatory cells per glomerulus with matched control patients with MN but no malignancy. Results. 40 malignancies were identified in 37 patients, 28 of which occurred after the MN diagnosis. The standardized incidence ratio (SIR) was 2.1 (95% CI, 1.3–2.85) which was similar between patients ≥ 60 years and those p value 0.56). Conclusions. The relative risk of malignancy in MN patients was similar across different age groups. The number of inflammatory cells per glomerulus did not differentiate between MN patients with and without malignancies.

Item does not contain fulltext BACKGROUND: Change in albuminuria as a surrogate endpoint for progression of chronic kidney disease is strongly supported by biological plausibility, but empirical evidence to support its validity in epidemiological studies is lacking. We aimed to assess the consistency of the association between change in albuminuria and risk of end-stage kidney disease in a large individual participant-level meta-analysis of observational studies. METHODS: In this meta-analysis, we collected individual-level data from eligible cohorts in the Chronic Kidney Disease Prognosis Consortium (CKD-PC) with data on serum creatinine and change in albuminuria and more than 50 events on outcomes of interest. Cohort data were eligible if participants were aged 18 years or older, they had a repeated measure of albuminuria during an elapsed period of 8 months to 4 years, subsequent end-stage kidney disease or mortality follow-up data, and the cohort was active during this consortium phase. We extracted participant-level data and quantified percentage change in albuminuria, measured as change in urine albumin-to-creatinine ratio (ACR) or urine protein-to-creatinine ratio (PCR), during baseline periods of 1, 2, and 3 years. Our primary outcome of interest was development of end-stage kidney disease after a baseline period of 2 years. We defined an end-stage kidney disease event as initiation of kidney replacement therapy. We quantified associations of percentage change in albuminuria with subsequent end-stage kidney disease using Cox regression in each cohort, followed by random-effects meta-analysis. We further adjusted for regression dilution to account for imprecision in the estimation of albuminuria at the participant level. We did multiple subgroup analyses, and also repeated our analyses using participant-level data from 14 clinical trials, including nine clinical trials not in CKD-PC. FINDINGS: Between July, 2015, and June, 2018, we transferred and analysed data from 28 cohorts in the CKD-PC, which included 693 816 individuals (557 583 [80%] with diabetes). Data for 675 904 individuals and 7461 end-stage kidney disease events were available for our primary outcome analysis. Change in ACR was consistently associated with subsequent risk of end-stage kidney disease. The adjusted hazard ratio (HR) for end-stage kidney disease after a 30% decrease in ACR during a baseline period of 2 years was 0.83 (95% CI 0.74-0.94), decreasing to 0.78 (0.66-0.92) after further adjustment for regression dilution. Adjusted HRs were fairly consistent across cohorts and subgroups (ie, estimated glomerular filtration rate, diabetes, and sex), but the association was somewhat stronger among participants with higher baseline ACR than among those with lower baseline ACR (pinteraction

Rationale & Objective Chronic kidney disease (CKD) is complicated by abnormalities that reflect disruption in filtration, tubular, and endocrine functions of the kidney. Our aim was to explore the relationship of specific laboratory result abnormalities and hypertension with the estimated glomerular filtration rate (eGFR) and albuminuria CKD staging framework. Study Design Cross-sectional individual participant-level analyses in a global consortium. Setting & Study Populations 17 CKD and 38 general population and high-risk cohorts. Selection Criteria for Studies Cohorts in the CKD Prognosis Consortium with data for eGFR and albuminuria, as well as a measurement of hemoglobin, bicarbonate, phosphorus, parathyroid hormone, potassium, or calcium, or hypertension. Data Extraction Data were obtained and analyzed between July 2015 and January 2018. Analytical Approach We modeled the association of eGFR and albuminuria with hemoglobin, bicarbonate, phosphorus, parathyroid hormone, potassium, and calcium values using linear regression and with hypertension and categorical definitions of each abnormality using logistic regression. Results were pooled using random-effects meta-analyses. Results The CKD cohorts (n = 254,666 participants) were 27% women and 10% black, with a mean age of 69 (SD, 12) years. The general population/high-risk cohorts (n = 1,758,334) were 50% women and 2% black, with a mean age of 50 (16) years. There was a strong graded association between lower eGFR and all laboratory result abnormalities (ORs ranging from 3.27 [95% CI, 2.68-3.97] to 8.91 [95% CI, 7.22-10.99] comparing eGFRs of 15 to 29 with eGFRs of 45 to 59 mL/min/1.73 m 2), whereas albuminuria had equivocal or weak associations with abnormalities (ORs ranging from 0.77 [95% CI, 0.60-0.99] to 1.92 [95% CI, 1.65-2.24] comparing urinary albumin-creatinine ratio > 300 vs < 30 mg/g). Limitations Variations in study era, health care delivery system, typical diet, and laboratory assays. Conclusions Lower eGFR was strongly associated with higher odds of multiple laboratory result abnormalities. Knowledge of risk associations might help guide management in the heterogeneous group of patients with CKD. © 2018. This is the authors’ accepted and refereed manuscript to the article. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/ "

Introduction: Patients with chronic kidney disease (CKD) and estimated glomerular filtration rate (eGFR) Methods: We undertook a meta-analysis of risk factors for kidney failure treated with kidney replacement therapy (KRT), cardiovascular disease (CVD) events, and death in participants with CKD G4þ from 28 cohorts (n ¼ 185,024) across the world who were part of the CKD Prognosis Consortium.Results: In the fully adjusted meta-analysis, risk factors associated with KRT were time-varying CVD, male sex, black race, diabetes, lower eGFR, and higher albuminuria and systolic blood pressure. Age was associated with a lower risk of KRT (adjusted hazard ratio: 0.74; 95% confidence interval: 0.69–0.80) overall, and also in the subgroup of individuals younger than 65 years. The risk factors for CVD events included male sex, history of CVD, diabetes, lower eGFR, higher albuminuria, and the onset of KRT. Systolic blood pressure showed a U-shaped association with CVD events. Risk factors for mortality were similar to those for CVD events but also included smoking. Most risk factors had qualitatively consistent associations across cohorts.Conclusion: Traditional CVD risk factors are of prognostic value in individuals with an eGFR

Objective Non-diabetic renal disease (NDRD) is common in patients with type 2 diabetes (T2D), but the relationship between its presentation and prognosis is unknown. Research design and methods In a retrospective cohort study, we compared renal and patient survival among 263 patients with T2D who had native renal biopsies between 2002 and 2008 from three Auckland hospitals in New Zealand. The presence of diabetic nephropathy (DN), NDRD or mixed (DN and NDRD) was determined from biopsy. We examined clinical associations according to NDRD etiologies and mode of presentation—acute (defined by acute kidney injury (AKI)) or non-acute. Patients were followed until end-stage renal disease, death or December 2015. Survival was compared using Log-rank test. Results 94 (36%) patients had DN, 72 (27%) had NDRD, and 97 (37%) had mixed pathologies. Obesity-related focal segmental glomerulosclerosis was the most common NDRD (46%) in patients with non-acute presentations, whereas interstitial nephritis or immune-complex glomerulonephritides were the most prevalent in those with acute presentations (60%). DN was commonly associated with AKI (p

Aims: To highlight the population demographics and socio-economic status of Maori and Pacific people in New Zealand, and relate this to their relative incidence and prevalence of kidney disease, relative access to renal replacement therapies and provide a comparison of their outcomes relative to non-Maori/non-Pacific people with kidney disease in New Zealand. Methods: A review was carried out of relevant New Zealand Statistics and Health data, literature on kidney disease in New Zealand including reports of the Australian and New Zealand Dialysis and Transplant Registry and further analysis of the New Zealand Diabetic Cohort Study. Results: There are large differences in the incidence of microalbuminuria, glomerulonephritis and hypertension amongst Maori and Pacific people in comparison to others. There is a 3.5 fold higher relative incidence of Maori and Pacific patients commencing renal replacement therapy. Identified associations with CKD include an increased incidence of obesity, smoking and poverty relative to other members of the population. Maori and Pacific people are less likely to be transplanted and have a reduced graft survival. Conclusions: Maori and Pacific people have a higher incidence of chronic kidney disease and end-stage renal failure in comparison to the rest of the population with poorer outcomes. The causes are likely to be multi-factorial with poverty an important contributor.

Summary Background and objectives The Initiating Dialysis Early and Late study showed that planned early or late initiation of dialysis, based on the Cockcroft and Gault estimation of GFR, was associated with identical clinical outcomes. This study examined the association of all-cause mortality with estimated GFR at dialysis commencement, which was determined using multiple formulas. Design, setting, participants, & measurements Initiating Dialysis Early and Late trial participants were stratified into tertiles according to the estimated GFR measured by Cockcroft and Gault, Modification of Diet in Renal Disease, or Chronic Kidney Disease-Epidemiology Collaboration formula at dialysis commencement. Patient survival was determined using multivariable Cox proportional hazards model regression. Results Only Initiating Dialysis Early and Late trial participants who commenced on dialysis were included in this study (n=768). A total of 275 patients died during the study. After adjustment for age, sex, racial origin, body mass index, diabetes, and cardiovascular disease, no significant differences in survival were observed between estimated GFR tertiles determined by Cockcroft and Gault (lowest tertile adjusted hazard ratio, 1.11; 95% confidence interval, 0.82 to 1.49; middle tertile hazard ratio, 1.29; 95% confidence interval, 0.96 to 1.74; highest tertile reference), Modification of Diet in Renal Disease (lowest tertile hazard ratio, 0.88; 95% confidence interval, 0.63 to 1.24; middle tertile hazard ratio, 1.20; 95% confidence interval, 0.90 to 1.61; highest tertile reference), and Chronic Kidney Disease-Epidemiology Collaboration equations (lowest tertile hazard ratio, 0.93; 95% confidence interval, 0.67 to 1.27; middle tertile hazard ratio, 1.15; 95% confidence interval, 0.86 to 1.54; highest tertile reference). Conclusion Estimated GFR at dialysis commencement was not significantly associated with patient survival, regardless of the formula used. However, a clinically important association cannot be excluded, because observed confidence intervals were wide. Clin J Am Soc Nephrol 9: 135–142, 2014. doi: 10.2215/CJN.02310213

OBJECTIVE Diabetes has become the leading cause of end-stage renal disease (ESRD). Renal risk stratification could assist in earlier identification and targeted prevention. This study aimed to derive risk models to predict ESRD events in type 2 diabetes in primary care. RESEARCH DESIGN AND METHODS The nationwide derivation cohort included adults with type 2 diabetes from the New Zealand Diabetes Cohort Study initially assessed during 2000–2006 and followed until December 2010, excluding those with pre-existing ESRD. The outcome was fatal or nonfatal ESRD event (peritoneal dialysis or hemodialysis for ESRD, renal transplantation, or death from ESRD). Risk models were developed using Cox proportional hazards models, and their performance was assessed in a separate validation cohort. RESULTS The derivation cohort included 25,736 individuals followed for up to 11 years (180,497 person-years; 86% followed for ≥5 years). At baseline, mean age was 62 years, median diabetes duration 5 years, and median HbA1c 7.2% (55 mmol/mol); 37% had albuminuria; and median estimated glomerular filtration rate (eGFR) was 77 mL/min/1.73 m2. There were 637 ESRD events (2.5%) during follow-up. Models that included sex, ethnicity, age, diabetes duration, albuminuria, serum creatinine, systolic blood pressure, HbA1c, smoking status, and previous cardiovascular disease status performed well with good discrimination and calibration in the derivation cohort and the validation cohort (n = 5,877) (C-statistics 0.89–0.92), improving predictive performance compared with previous models. CONCLUSIONS These 5-year renal risk models performed very well in two large primary care populations with type 2 diabetes. More accurate risk stratification could facilitate earlier intervention than using eGFR and/or albuminuria alone.

Background Abnormalities of cardiac structure and function are common in patients undergoing dialysis, and cardiovascular disease is the major cause of mortality in this group. Heart failure is a common clinical manifestation of cardiovascular disease and is preceded by left ventricular hypertrophy (LVH). There are variable reports about the impact of dialysis on LVH, both deleterious and beneficial. Our study investigated whether the timing of the initiation of dialysis therapy had an impact on cardiac structure and function. Study Design Randomized controlled trial. Setting & Participants This is a cardiac substudy involving 182 patients with stage 5 chronic kidney disease in the IDEAL (Initiating Dialysis Early and Late) trial. Intervention The IDEAL trial randomly assigned patients on the basis of estimated glomerular filtration rate (eGFR), calculated using the Cockcroft-Gault equation, to start dialysis therapy early (GFR, 10-14 mL/min/1.73 m 2 ), with the others starting late (GFR, 5-7 mL/min/1.73 m 2 ). Outcomes & Measurements Echocardiograms were obtained at baseline and 12 months after randomization. Primary outcomes were change in left ventricular mass indexed for height (LVMi) between baseline and 12 months, left ventricular ejection fraction, left ventricular systolic annular velocity, ratio of mitral inflow velocity (E) to mitral annular velocity (Ea) (E/Ea), and left atrial volume indexed for height (LAVi). Results LVMi at baseline was elevated, but similar in both groups, with no significant change within or between groups at 12 months. E/Ea and LAVi were increased at baseline, consistent with significant diastolic dysfunction; there were no differences between groups at 12 months and no changes were observed for left ventricular volumes, left ventricular ejection fraction, stroke volume, and other echocardiographic parameters. Limitations Small multicenter study using echocardiography. Conclusions Advanced cardiac disease in these patients with stage 5 chronic kidney disease did not progress during the 12-month study period and planned early initiation of dialysis therapy did not result in differences in any echocardiographic variables of cardiac structure and function.

Kidney injury in the context of cholestatic liver dysfunction is not uncommon; this has been historically referred to as cholemic nephrosis implying a direct deleterious renal effect of cholemia. However, scepticism about the exact role that bile and its constituents play in this injury has led to the disappearance of the term. We describe a case of severe AKI due to bile nephropathy with bile casts in flucloxacillin-induced liver dysfunction. We also discuss the recent literature reviving the concept of bile nephropathy.

Background. A high incidence of albuminuria, varying by ethnicity, has been found in a number of populations worldwide. There have been few opportunities to explore the prevalence of albuminuria as a marker of chronic kidney disease while adjusting for other risk factors in the different ethnic groups in New Zealand. Methods. We examined the association between albuminuria and ethnicity using cross-sectional data from a large cohort study of type 2 diabetes conducted in New Zealand. Results. The study population was 65 171 adults in primary care with type 2 diabetes, not on renal replacement therapy; median age was 64.7 years, median diabetes duration 5.1 years and 48.5% were non-European. Microalbuminuria or greater was present in 50% of Maori, 49% of Pacific people, 31% of Indo- and East-Asians and 28% of Europeans. Regression analyses were used to examine the association between ethnicity and albuminuria—measured as albumin:creatinine ratio—after controlling for study site and other known risk variables: age, sex, duration of diabetes, smoking status, socioeconomic status, body mass index, systolic and diastolic blood pressure, triglyceride levels, HbA1C and being on an angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker. After controlling for these risk factors and compared with Europeans, odds ratios for ‘advanced’ albuminuria (� 100 mg/mmol) were 3.9 (95% confidence interval: 3.2–4.6) in Maori, 4.7 (3.6–6.3) in Pacific people, 2.0 (1.5–2.7) in Indo-Asians and 4.1 (3.2–5.1) in East-Asians. Conclusion. Non-European ethnicities appear to carry significantly higher risks of albuminuria in type 2 diabetes.

Background Planned early initiation of dialysis therapy based on estimated kidney function does not influence mortality and major comorbid conditions, but amelioration of symptoms may improve quality of life and decrease costs. Study Design Patients with progressive chronic kidney disease and a Cockcroft-Gault estimated glomerular filtration rate of 10-15 mL/min/1.73 m2 were randomly assigned to start dialysis therapy at a glomerular filtration rate of either 10-14 (early start) or 5-7 mL/min/1.73 m2 (late start). Setting & Population Of the original 828 patients in the IDEAL (Initiation of Dialysis Early or Late) Trial in renal units in Australia and New Zealand, 642 agreed to participate in this cost-effectiveness study. Study Perspective & Timeframe A societal perspective was taken for costs. Patients were enrolled between July 1, 2000, and November 14, 2008, and followed up until November 14, 2009. Intervention Planned earlier start of maintenance dialysis therapy. Outcomes Difference in quality of life and costs. Results Median follow-up of patients (307 early start, 335 late start) was 4.15 years, with a 6-month difference in median duration of dialysis therapy. Mean direct dialysis costs were significantly higher in the early-start group ($10,777; 95% CI, $313 to $22,801). Total costs, including costs for resources used to manage adverse events, were higher in the early-start group ($18,715; 95% CI, −$3,162 to $43,021), although not statistically different. Adjusted for differences in baseline quality of life, the difference in quality-adjusted survival between groups over the time horizon of the trial was not statistically different (0.02 full health equivalent years; 95% CI, −0.09 to 0.14). Limitations Missing quality-of-life questionnaires and skewed cost data, although similar in each group, decrease the precision of results. Conclusion Planned early initiation of dialysis therapy in patients with progressive chronic kidney disease has higher dialysis costs and is not associated with improved quality of life.

The Chronic Kidney Disease (CKD) Prognosis Consortium is a collaborative author of the above-mentioned article. The CKD Prognosis Consortium investigators/collaborators are as follows: • African American Study of Kidney Disease and Hypertension (AASK): Brad Astor, Lawrence J. Appel; British Columbia CKD Study (BC CKD): Adeera Levin, Ognjenka Djurdjev; Canadian Study of Prediction of Death, Dialysis and Interim Cardiovascular Events (CanPREDDICT): Adeera Levin, Mila Tang, Ognjenka Djurdjev; Cleveland Clinic CKD Registry Study (CCF): Sankar D. Navaneethan, Stacey E. Jolly, Jesse D. Schold, Joseph V. Nally Jr; Chronic Renal Impairment in Birmingham (CRIB): David C. Wheeler, Jonathan Emberson, John Townend, Martin Landray; Chronic Renal Insufficiency Cohort Study (CRIC): Harold I. Feldman, Chi-yuan Hsu, James P. Lash, Lawrence J. Appel; Chronic Renal Insufficiency Standards Implementation Study (CRISIS): Philip A. Kalra, James P. Ritchie, Raman Maharajan, Helen Alderson, Beverly Lane; German Chronic Kidney Disease Study (GCKD): Kai-Uwe Eckardt, Markus P. Schneider, Anna Kottgen, Florian Kronenberg, Barbara Barthlein; Geisinger Health System: Alex R. Chang, Jamie A. Green, H. Lester Kirchner, Kevin Ho; Grampian Laboratory Outcomes, Morbidity and Mortality Studies – 2 (GLOMMS2): Angharad Marks, Corri Black, Gordon J. Prescott, Nick Fluck; Gonryo Study: Masaaki Nakayama, Mariko Miyazaki, Tae Yamamoto, Gen Yamada; Hong Kong CKD Studies: Angela Yee-Moon Wang, Sharon Cheung, Sharon Wong, Jessie Chu, Henry Wu; Maccabi Health System: Varda Shalev, Gabriel Chodick; Multifactorial Approach and Superior Treatment Efficacy in Renal Patients with the Aid of a Nurse Practitioner (MASTERPLAN): Peter J. Blankestijn, Jack F.M. Wetzels, Arjan D. van Zuilen, Jan A. van den Brand; Modification of Diet in Renal Disease Study (MDRD): Andrew S. Levey, Lesley A. Inker, Mark J. Sarnak, Hocine Tighiouart; Nanjing CKD Network Cohort Study (Nanjing CKD): Haitao Zhang; NephroTest Study: Benedicte Stengel; National Renal Healthcare Program – Uruguay (NRHP-URU): Pablo G. Rios, Nelson Mazzuchi, Liliana Gadola, Veronica Lamadrid, Laura Sola; New Zealand Diabetes Cohort Study (NZDCS): John F. Collins, C. Raina Elley, Timothy Kenealy; Parcours de Soins des Personnes Agees (PSPA): Olivier Moranne, Cecile Couchoud, Cecile Vigneau; Primary-Secondary Care Partnership to Prevent Adverse Outcomes in Chronic Kidney Disease (PSP CKD): Nigel J. Brunskill, Rupert W. Major, David Shepherd, James F. Medcalf; Racial and Cardiovascular Risk Anomalies in CKD Cohort (RCAV): Csaba P. Kovesdy, Kamyar Kalantar-Zadeh, Miklos Z. Molnar, Keiichi Sumida, Praveen K. Potukuchi; Reduction of Endpoints in Non-insulin Dependent Diabetes Mellitus with the Angiotensin II Antagonist Losartan (RENAAL): Hiddo J.L. Heerspink, Dick de Zeeuw, Barry Brenner; Stockholm CREAtinine Measurements Cohort (SCREAM): Juan Jesus Carrero, Peter Barany, Abdul Rashid Qureshi, Carl-Gustaf Elinder; Second Manifestations of ARTerial Disease Study (SMART): Frank L.J. Visseren, Yolanda van der Graaf; Swedish Renal Registry CKD Cohort (SRR CKD): Marie Evans, Maria Stendahl, Staffan Schon, Marten Segelmark, Karl-Goran Prutz; Sunnybrook Cohort: David M. Naimark, Navdeep Tangri; West of Scotland CKD Study: Patrick B. Mark, Jamie P. Traynor, Colin C. Geddes, Peter C. Thomson.• CKD Prognosis Consortium Steering Committee: Alex R. Chang, Josef Coresh (Chair), Ron T. Gansevoort, Morgan E. Grams, Anna Kottgen, Andrew S. Levey, Kunihiro Matsushita, Mark Woodward, Luxia Zhang.• CKD Prognosis Consortium Data Coordinating Center: Shoshana H. Ballew (Assistant Project Director), Jingsha Chen (Programmer), Josef Coresh (Principal Investigator), Morgan E. Grams (Director of Nephrology Initiatives), Lucia Kwak (Programmer), Kunihiro Matsushita (Director), Yingying Sang (Lead Programmer), Aditya Surapaneni (Programmer), Mark Woodward (Senior Statistician).• Kidney Disease Improving Global Outcomes (KDIGO) Controversies Conference on Prognosis and Optimal Management of Patients with Advanced CKD: Kai-Uwe Eckardt (Conference Co-Chair), Brenda R. Hemmelgarn (Conference Co-Chair), David C. Wheeler (KDIGO Co-Chair), Wolfgang C. Winkelmayer (KDIGO Co-Chair), John Davis (CEO), Danielle Green (Managing Director), Michael Cheung (Chief Scientific Officer), Tanya Green (Communications Director), Melissa McMahan (Programs Director).

BACKGROUND In clinical practice, there is considerable variation in the timing of the initiation of maintenance dialysis for patients with stage V chronic kidney disease, with a worldwide trend toward early initiation. In this study, conducted at 32 centers in Australia and New Zealand, we examined whether the timing of the initiation of maintenance dialysis influenced survival among patients with chronic kidney disease. METHODS We randomly assigned patients 18 years of age or older with progressive chronic kidney disease and an estimated glomerular filtration rate (GFR) between 10.0 and 15.0 ml per minute per 1.73 m 2 of body-surface area (calculated with the use of the Cockcroft–Gault equation) to planned initiation of dialysis when the estimated GFR was 10.0 to 14.0 ml per minute (early start) or when the estimated GFR was 5.0 to 7.0 ml per minute (late start). The primary outcome was death from any cause. RESULTS Between July 2000 and November 2008, a total of 828 adults (mean age, 60.4 years; 542 men and 286 women; 355 with diabetes) underwent randomization, with a median time to the initiation of dialysis of 1.80 months (95% confidence interval [CI], 1.60 to 2.23) in the early-start group and 7.40 months (95% CI, 6.23 to 8.27) in the late-start group. A total of 75.9% of the patients in the late-start group initiated dialysis when the estimated GFR was above the target of 7.0 ml per minute, owing to the development of symptoms. During a median follow-up period of 3.59 years, 152 of 404 patients in the early-start group (37.6%) and 155 of 424 in the late-start group (36.6%) died (hazard ratio with early initiation, 1.04; 95% CI, 0.83 to 1.30; P = 0.75). There was no significant difference between the groups in the frequency of adverse events (cardiovascular events, infections, or complications of dialysis). CONCLUSIONS In this study, planned early initiation of dialysis in patients with stage V chronic kidney disease was not associated with an improvement in survival or clinical outcomes. (Funded by the National Health and Medical Research Council of Australia and others; Australian New Zealand Clinical Trials Registry number, 12609000266268.)

Background Peritonitis is a significant source of morbidity and mortality in patients on peritoneal dialysis (PD). Symptoms may persist, requiring an emergency laparotomy. Although increasingly used, we find that, in PD patients, abdominal computerized tomography (CT) is ineffective in determining significant pathology. This study was undertaken to assess the diagnostic utility of CT for the identification of intra-abdominal collections in PD patients presenting with peritonitis. Methods A retrospective chart review was undertaken of all patients that underwent abdominal CT scanning in the context of severe PD peritonitis in the past 2 years. All of these patients had at least one CT scan preoperatively. Results 133 patients presented with PD peritonitis; 19 patients had a contrast CT procedure (12 females, 7 males). Average age was 59.2 years; mean duration on PD was 43.8 months. 13 of 19 patients had gram-negative bacillary peritonitis, 6 of whom had polymicrobial peritonitis; 4 patients had fungal peritonitis and 2 had Staphylococcus aureus peritonitis. 26 CT scans were done in 19 patients an average of 10 days after presentation. 21 of 26 scans revealed no collections of surgical interest. 12 laparotomies were performed, with an average delay of 10.4 days from presentation to laparotomy. Of the 12 laparotomies, 6 found a drainable collection not seen on CT. Seven of the 19 patients died (37%) and no patient was able to return to PD. Conclusion PD patients requiring emergency laparotomy following PD peritonitis have a high mortality rate. A negative abdominal CT in the setting of ongoing symptoms should not be taken as reassuring, nor should it delay proceeding to emergency laparotomy.

Hypophosphatasia is an inborn error of metabolism caused by mutations in the ALPL gene. It is characterized by low serum alkaline phosphatase (ALP) activity and defective mineralization of bone, but the phenotype varies greatly in severity depending on the degree of residual enzyme activity. We describe a man with compound heterozygous mutations in ALPL, but no previous bone disease, who suffered numerous disabling fractures after he developed progressive renal failure (for which he eventually needed dialysis treatment) and was prescribed alendronate treatment. A bone biopsy showed marked osteomalacia with low osteoblast numbers and greatly elevated pyrophosphate concentrations at mineralizing surfaces. In vitro testing showed that one mutation, T117H, produced an ALP protein with almost no enzyme activity; the second, G438S, produced a protein with normal activity, but its activity was inhibited by raising the media phosphate concentration, suggesting that phosphate retention (attributable to uremia) could have contributed to the phenotypic change, although a pathogenic effect of bisphosphonate treatment is also likely. Alendronate treatment was discontinued and, while a suitable kidney donor was sought, the patient was treated for 6 months with teriparatide, which significantly reduced the osteomalacia. Eighteen months after successful renal transplantation, the patient was free of symptoms and the scintigraphic bone lesions had resolved. A third bone biopsy showed marked hyperosteoidosis but with plentiful new bone formation and a normal bone formation rate. This case illustrates how pharmacological (bisphosphonate treatment) and physiologic (renal failure) changes in the "environment" can dramatically affect the phenotype of a genetic disorder.

Background/Aim The Delay Future End Stage Nephropathy due to Diabetes study was a randomised controlled trial of Māori and Pacific patients with advanced diabetic nephropathy, comparing a community-based model of care with usual care. The intervention group achieved lower blood pressure (BP), proteinuria and less end-organ damage. After the intervention ended, all patients reverted to usual care, and were followed to review the sustainability of the intervention. Methods A retrospective observation of 65 patients (aged 47–75 years) with type 2 diabetes, hypertension, chronic kidney disease 3/4 and proteinuria (>0.5 g/day) previously randomised to intervention/community care or usual care for 11–21 months. Follow up thereafter was until death, end-stage renal disease (ESRD) (estimated glomerular filtration rate (eGFR) ≤ 10 mL/min/1.73 m2)/dialysis or 1 February 2014. Primary end-points were death and ESRD/dialysis. Secondary outcomes were annualised glomerular filtration rate decline, non-fatal vascular events and hospitalisations. Results Median (interquartile ranges (IQR)) post-trial follow up was 49 (21–81) months and similar in both groups. The median (IQR) eGFR decline was −3.1 (−5.5, −2.3) and −5.5 (−7.1, −3.0) mL/min/year in the intervention and usual care groups respectively (P = 0.11). Similar number of deaths, renal and vascular events were observed in both groups. At the end of follow up, the number of prescribed antihypertensive medications was similar (3.4 ± 1.0 vs 3.3 ± 1.4; P = 0.78). There were fewer median (IQR) hospital days (8 (3, 18) vs 15.5 (6, 49) days, P = 0.03) in the intervention group. Conclusions Short-term intensive BP control followed by usual care did not translate into reduction in long-term mortality or ESRD rates, but was associated with reduced hospitalisations.

Objective The aim of the present investigation was to examine the association between body mass index (BMI) and peritonitis rates among incident peritoneal dialysis (PD) patients in a large cohort with long-term follow-up. Design Retrospective observational cohort study of the Australian and New Zealand PD patient population. Setting Australia and New Zealand Dialysis and Transplant (ANZDATA) Registry. Participants The study included all incident adult patients ( n = 10 709) who received PD in Australia and New Zealand in the 12-year period between 1 April 1991 and 31 March 2003. Patients were classified as obese (BMI ≥ 30 kg/m2), overweight (BMI 25.0 – 29.9 kg/m2), normal weight (20 – 24.9 kg/m2), or underweight (< 20 kg/m2). Main Measurements Time to first peritonitis and episodes of peritonitis per patient-year were recorded over the 12-year period. Results Higher BMI was associated with a shorter time to first peritonitis episode, independent of other risk factors [hazard ratio 1.08 for each 5-kg/m2 increase in BMI, 95% confidence interval (CI) 1.04 – 1.12, p < 0.001]. When peritonitis outcomes were analyzed as episodes of peritonitis per patient-year, these rates were significantly higher among patients with higher BMI: underweight 0.69 episodes/year (95% CI 0.66 – 0.73), normal weight 0.79 (95% CI 0.77 – 0.81), overweight 0.88 (95% CI 0.85 – 0.90), obese 1.06 (95% CI 1.02 – 1.09). Coronary artery disease and chronic lung disease were associated with both shorter time to first peritonitis and higher peritonitis rates, independently of these other factors. There was also a “vintage effect,” with lower peritonitis rates seen among people who commenced dialysis in more recent years. Conclusions Higher BMI at the commencement of renal replacement therapy is a significant risk factor for peritonitis. The mechanisms for this remain undefined.

Objectives The primary objective of the IDEAL study is to determine whether the timing of dialysis initiation has an effect on survival in subjects with end-stage renal disease (ESRD). The secondary objectives are to determine the impact of “early start” versus “late start” dialysis on nutritional and cardiac morbidity, quality of life, and economic cost. Design Prospective multicenter randomized controlled trial. Patients are randomized to commence dialysis at a glomerular filtration rate (by Cockcroft–Gault) of either 10 – 14 mL/minute/1.73 m2 (“early start”) or 5 – 7 mL/min/1.73 m2 (“late start”), with stratification for dialysis modality (hemodialysis vs peritoneal dialysis), study center, and the presence or not of diabetes mellitus. Setting Dialysis units throughout Australia and New Zealand. Patients Patients with ESRD commencing chronic dialysis therapy. Outcome Measures Three years from randomization, all-cause mortality, morbidity, and economic impact; structural and functional cardiac status, nutritional state, and quality of life will be assessed. Results To date, 388 patients of a minimum 800 patients have been entered and randomized into the study. Current recruitment rates suggest sufficient patients will be enrolled by December 2004 and follow-up completed by December 2007. Conclusions The IDEAL study will provide evidence for the optimal time to commence dialysis.

Icodextrin is a starch-derived, high molecular weight glucose polymer, which has been shown to promote sustained ultrafiltration equivalent to that achieved with hypertonic (3.86%/4.25%) glucose exchanges during prolonged intraperitoneal dwells (up to 16 h). Patients with impaired ultrafiltration, particularly in the settings of acute peritonitis, high transporter status and diabetes mellitus, appear to derive the greatest benefit from icodextrin with respect to augmentation of dialytic fluid removal, amelioration of symptomatic fluid retention and possible prolongation of technique survival. Glycaemic control is also improved by substituting icodextrin for hypertonic glucose exchanges in diabetic patients. Preliminary in vitro and ex vivo studies suggest that icodextrin demonstrates greater peritoneal membrane biocompatibility than glucose-based dialysates, but these findings need to be confirmed by long-term clinical studies. This paper reviews the available clinical evidence pertaining to the safety and efficacy of icodextrin and makes recommendations for its use in peritonal dialysis.

Darbepoetin alfa (Aranesp(R), Amgen Ltd) is a long-acting, hyperglycosylated recombinant human erythropoietin (r-HuEPO; epoetin) analogue, developed for the treatment of anaemia in patients with chronic kidney disease (CKD, i.e. end-stage renal failure or progressive renal impairment). Based on previously published European guidelines, this review article presents key recommendations for the use of darbepoetin alfa in Australasian clinical practice.

Summary: Fusidic acid has characteristics that suggest it might be a useful agent in the management of staphylococcal peritonitis in patients undergoing peritoneal dialysis. the present investigation was undertaken to establish the relationship between serum and peritoneal dialysis effluent concentrations of fusidic acid and to determine whether therapeutic levels of fusidic acid could be achieved in the dialysate following oral administration of the agent. Concentrations of fusidic acid up to 80 times the MIC for staphylococci were found after repeated oral doses. the results have provided basic data needed to initiate clinical studies of the role of fusidic acid as an adjunctive agent in the management of staphylococcal peritonitis.

Sclerosis of the peritoneum with encapsulation of the small intestine is one of the most serious complications of continuous ambulatory peritoneal dialysis (CAPD) and is associated with a high mortality rate. Its presence should be suspected in patients treated by CAPD who develop small bowel dysfunction with associated abdominal pain and progressive loss of ultrafiltration. In its severest form, it leads to complete high small intestinal obstruction and requirement for total parenteral nutrition. We report the successful surgical management of two young, severely emaciated patients who had this complication of CAPD. Each had entrapment of their bowel by a thick, fibrosed, and calcified membrane. Both were treated by surgically peeling the membrane away from the intestines.

♦ Background Since the mid-1990s, early dialysis initiation has dramatically increased in many countries. The Initiating Dialysis Early and Late (IDEAL) study demonstrated that, compared with late initiation, planned early initiation of dialysis was associated with comparable clinical outcomes and increased health care costs. Because residual renal function is a key determinant of outcome and is better preserved with peritoneal dialysis (PD), the present pre-specified subgroup analysis of the IDEAL trial examined the effects of early- compared with late-start dialysis on clinical outcomes in patients whose planned therapy at the time of randomization was PD. ♦ Methods Adults with an estimated glomerular filtration rate (eGFR) of 10 – 15 mL/min/1.73 m2 who planned to be treated with PD were randomly allocated to commence dialysis at an eGFR of 10 – 14 mL/min/1.73 m2 (early start) or 5 – 7 mL/min/1.73 m2 (late start). The primary outcome was all-cause mortality. ♦ Results Of the 828 IDEAL trial participants, 466 (56%) planned to commence PD and were randomized to early start ( n = 233) or late start ( n = 233). The median times from randomization to dialysis initiation were, respectively, 2.03 months [interquartile range (IQR):1.67 – 2.30 months] and 7.83 months (IQR: 5.83 – 8.83 months). Death occurred in 102 early-start patients and 96 late-start patients [hazard ratio: 1.04; 95% confidence interval (CI): 0.79 – 1.37]. No differences in composite cardiovascular events, composite infectious deaths, or dialysis-associated complications were observed between the groups. Peritonitis rates were 0.73 episodes (95% CI: 0.65 – 0.82 episodes) per patient–year in the early-start group and 0.69 episodes (95% CI: 0.61 – 0.78 episodes) per patient–year in the late-start group (incidence rate ratio: 1.19; 95% CI: 0.86 – 1.65; p = 0.29). The proportion of patients planning to commence PD who actually initiated dialysis with PD was higher in the early-start group (80% vs 70%, p = 0.01). ♦ Conclusion Early initiation of dialysis in patients with stage 5 chronic kidney disease who planned to be treated with PD was associated with clinical outcomes comparable to those seen with late dialysis initiation. Compared with early-start patients, late-start patients who had chosen PD as their planned dialysis modality were less likely to commence on PD.

Background. In this study, our main goal was to determine whether an integrated, community-based model of care using culturally appropriate health-care assistants to manage hypertension in Māori and Pacific patients with diabetes and chronic kidney disease (CKD) is more effective than conventional care in achieving blood pressure (BP) targets and delaying progression of cardiac and renal end-organ damage. Methods. Sixty-five Māori and Pacific patients (aged 47-75 years) with type 2 diabetes, moderate CKD (>0.5 g proteinuria/day, serum creatinine 130-300 μmol/l) and hypertension were randomized to usual care (n = 32) or community/intervention care (n = 33) for 12 months. Community care patients were visited monthly by a nurse-led health-care assistant for BP measurement. Antihypertensives were adjusted using a stepwise protocol, aiming for a BP

To evaluate determinants of left ventricular hypertrophy (LVH) and left ventricular (LV) systolic dysfunction in chronic renal failure (CRF), M-mode and two-dimensional echocardiography were performed in 38 undialyzed patients with CRF (serum creatinineor = 3.4 mg/dL), 54 patients receiving continuous ambulatory peritoneal dialysis, 30 patients receiving hemodialysis, and 59 healthy age- and sex-matched volunteers. Left ventricular (LV) wall thickness and LV dimensions were greatest in dialysis patients, intermediate in CRF patients, and least in control subjects. LV mass index calculated from M-mode measurements was 78.7 g/m2 +/- 14.8 g/m2 in controls, 120.5 g/m2 +/- 28.7 g/m2 in CRF patients, and 136 +/- 45.0 g/m2 in dialysis patients (P0.0001). LV fractional shortening and LV velocity of circumferential shortening were lower in dialysis patients than in CRF patients and controls (fractional shortening 36.5% +/- 5.6% in controls, 36.2% +/- 7.2% in CRF patients, and 29.8% +/- 8.9% in dialysis patients; P0.0001). Echocardiography was normal in only 24 dialysis patients (29%) and 14 CRF patients (37%) (P = NS). Thirty-nine dialysis patients (46%) and 10 CRF patients (26%) had LVH (P = NS). Thirty dialysis patients (36%) and five CRF patients (13%) had LV systolic dysfunction (P0.05). LV hypertrophy with LV systolic dysfunction was present in 15 dialysis patients but no CRF patients (P0.05). There were no significant differences between hemodialysis patients and continuous ambulatory peritoneal dialysis patients in M-mode echocardiographic measurements or the frequency of LVH and LV systolic dysfunction.(ABSTRACT TRUNCATED AT 250 WORDS)

Fungal infection is an uncommon cause of peritonitis in patients on continuous ambulatory peritoneal dialysis (CAPD). We report our center's experience with 38 episodes of fungal peritonitis occurring in 33 patients, out of a total of 503 patients managed on CAPD over 11 1/2 years, and review the relevant literature. Our usual management philosophy has been one of early peritoneal catheter removal without antifungal therapy. In those with worsening clinical features, and in those with persistence of signs and symptoms beyond 48 hours after catheter removal, antifungal drugs were administered. Only five patients received antifungal therapy initially, followed by later catheter removal. Seventy-six percent of patients treated by catheter removal alone (N = 21) and 64% of patients treated by catheter removal followed by antifungal therapy (N = 11) were successfully reestablished on CAPD. A policy of early catheter removal, usually alone, but followed by antifungal therapy in select cases, can be associated with a mortality rate of less than 15% and a high rate of return to effective peritoneal dialysis.

A case of arterioureteral fistula from the graft artery stump of a failed transplant and the native ureter is reported. This case illustrates one of the possible complications of graft anastomosis. The etiological factors involved in the formation of the aneurysm and eventually the fistula are discussed. ( J. Urol., 144: 1229–1230, 1990 )

Sialyltransferase-1 activity was studied in cultured 12-18 human glioma cells. The apparent Km and Vmax with variable LacCer concentrations were 32 microM and 197 pmoles/mg protein/hr and with variable CMP-NeuAc concentrations were 172 microM and 877 pmoles/mg protein/hr., respectively. The pH optimum towards exogenous LacCer was 6.0 and towards endogenous acceptors was 6.2. The optimum protein:detergent ratio was 1:1. Human beta interferon (1000 units/ml medium) increased sialyltransferase-1 activity only slightly on a protein basis but increased it 47% on a per cell basis. These results demonstrate that one of the biochemical effects of beta-interferon on 12-18 human glioma cells is to stimulate ganglioside synthesis.

Patients with chronic renal failure manifest reduced pressor response to norepinephrine (NE); this abnormality is at least partly responsible for the autonomic nervous system dysfunction observed in these patients. Since uremia is associated with increased levels of parathyroid hormone (PTH) and since PTH blunts the pressor effect of NE most likely via activation of prostaglandins, we have studied the relationship between blood levels of PTH and the reduced pressor response to NE in 17 uremic patients and we examined the effect of treatment with indomethacin on the response to NE in 9 uremic and 5 normal subjects. There was a significant negative correlation (r = -0.63, p less than 0.01) between the changes in blood pressure and the blood levels of PTH in uremic patients. Treatment with indomethacin was followed by significant improvement or normalization of the pressor response to NE in uremic patients. These data are consistent with the notion that the decreased pressor response to NE in uremia is due to increased production of prostaglandins induced by excess PTH and provide a therapeutic tool for the treatment of some of the manifestations of autonomic nervous system dysfunction in uremia.

Defective leukocyte function manifested by impaired migration (1, 2) and reduced phagocytic (3–5) and bactericidal activity (6) has been observed in patients with uraemia. Also, sera from dialysis patients contain a heat stable factor that inhibited granulocyte Chemotaxis (7). The mechanisms and/or the potential uraemic factors underlying these defects in leukocyte functions are not known.

Derangements in leukocyte function occur in patients with primary hyperparathyroidism and in those with uremia, which is a state of secondary hyperparathyroidism, suggesting that parathyroid hormone (PTH) may affect leukocyte function. We examined the interaction between PTH and random migration of human polymorphonuclear leukocytes (PMNL) utilizing a modified Boyden chamber. Intact 1-84 PTH but not its amino-terminal (1-34 PTH) or its carboxy-terminal (53-84 PTH) fragments produced marked and significant (p less than 0.01) stimulation of random migration in a dose-dependent manner. Inactivation of 1-84 PTH abolished its effect and other peptide hormones (calcitonin, glucagon, insulin and vasopressin) did not stimulate migration of PMNL. The effect of PTH on migration was not due to action of the hormone on chemotaxis. PTH did not enhance cAMP or cGMP production by PMNL. The stimulation of PMNL motility by PTH was independent of calcium concentration in media, was not mimicked by calcium ionophore and was not blocked by verapamil. Quinidine also produced significant (p less than 0.01) increase in random migration of PMNL and this effect was not additive to that of PTH. Prolonged exposure to PTH (16-20 h) was associated with significant inhibition of random migration of PMNL. The migration of PMNL from patients with advanced renal failure was significantly (p less than 0.01) reduced and there was a significant (p less than 0.01) inverse relationship between random migration of PMNL and serum levels of PTH. Also PTH produced only modest stimulation of random migration of PMNL in most patients with renal failure.(ABSTRACT TRUNCATED AT 250 WORDS)