Progression of Kidney Disease in Indigenous Australians: The eGFR Follow-up Study.

BACKGROUND AND OBJECTIVES: Indigenous Australians experience a heavy burden of CKD. To address this burden, the eGFR Follow-Up Study recruited and followed an Indigenous Australian cohort from regions of Australia with the greatest ESRD burden. We sought to better understand factors contributing to the progression of kidney disease. Specific objectives were to assess rates of progression of eGFR in Indigenous Australians with and without CKD and identify factors associated with a decline in eGFR. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This observational longitudinal study of Indigenous Australian adults was conducted in >20 sites. The baseline cohort was recruited from community and primary care clinic sites across five strata of health, diabetes status, and kidney function. Participants were then invited to follow up at 2-4 years; if unavailable, vital status, progression to RRT, and serum creatinine were obtained from medical records. Primary outcomes were annual eGFR change and combined renal outcome (first of ≥30% eGFR decline with follow-up eGFR<60 ml/min per 1.73 m(2), progression to RRT, or renal death). RESULTS: Participants (n=550) were followed for a median of 3.0 years. Baseline and follow-up eGFR (geometric mean [95% confidence interval], 83.9 (80.7 to 87.3) and 70.1 (65.9 to 74.5) ml/min per 1.73 m(2), respectively. Overall mean annual eGFR change was -3.1 (-3.6 to -2.5) ml/min per 1.73 m(2). Stratified by baseline eGFR (≥90, 60-89, <60 ml/min per 1.73 m(2)), annual eGFR changes were -3.0 (-3.6 to -2.4), -1.9 (-3.3 to -0.5), and -5.0 (-6.5 to -3.6) ml/min per 1.73 m(2). Across baseline eGFR categories, annual eGFR decline was greatest among adults with baseline albumin-to-creatinine ratio (ACR) >265 mg/g (30 mg/mmol). Baseline determinants of the combined renal outcome (experienced by 66 participants) were higher urine ACR, diabetes, lower measured GFR, and higher C-reactive protein. CONCLUSIONS: The observed eGFR decline was three times higher than described in nonindigenous populations. ACR was confirmed as a powerful predictor for eGFR decline across diverse geographic regions.

A 12-month review of peritoneal dialysis-related peritonitis in Western Australia: is empiric vancomycin still indicated for some patients?

BACKGROUND: The International Society for Peritoneal Dialysis (ISPD) guidelines recommend empiric therapy with cefazolin and ceftazidime for peritoneal dialysis (PD)-related peritonitis. Empiric cefazolin therapy may have diminishing efficacy because of emerging methicillin resistance in gram-positive bacteria (GPB). Western Australia also has large numbers of Aboriginal and isolated regional patients, where giving these antimicrobials can be impractical. OBJECTIVES: To evaluate, based on local antimicrobial resistance patterns, the feasibility of following ISPD guidelines in Western Australia and to identify any subgroups of PD peritonitis patients that may benefit from alternative empiric intraperitoneal antibiotics (e.g., vancomycin). STUDY DESIGN: Retrospective study of all PD peritonitis episodes in Western Australia from 1 February 2000 to 31 January 2001. SETTING: Three adult tertiary referral university hospitals and their PD patients in metropolitan Perth and regional Western Australia. PATIENTS: All adults on PD in Western Australia. MAIN OUTCOME MEASURE: Isolates and antibiograms were analyzed versus patient characteristics, including race and patient demographics. RESULTS: 293 patients (28% Aborigines, 32% regional patients) received PD. 145 episodes of PD peritonitis occurred during the study. The overall PD peritonitis rate was 1 episode/16 patient months, with Aborigines having 1 episode/10.5 patient months versus non-Aborigines having 1 episode/17 patient months (p < 0.001). 36% of isolates from PD peritonitis episodes were resistant to cefazolin or ceftazidime. 22% were methicillin-resistant GPB (MR-GPB) [18% coagulase-negative staphylococci (CoNS), 1.6% MR Staphylococcus aureus]; 2.5% were multidrug-resistant gram-negative bacteria (MDR-GNB); 5.7% were polymicrobial (MR-GPB and/or MDR-GNB); and 5.7% were fungal. 63% of CoNS were methicillin resistant. Non-Aboriginal patients yielded MR-GPB in 22% of isolates versus 23% in Aborigines (p = 0.9). Six of seven cases of fungal peritonitis occurred in Aboriginal patients (p < 0.001). CONCLUSIONS: In our study population the ISPD guidelines were appropriate for 64% of patients with PD peritonitis. We could not identify specific patient subgroups where empiric cefazolin use could be more effective. High proportions of MR-GPB PD peritonitis episodes, along with local factors, make empiric cefazolin unsuitable for many regional PD patients in Western Australia.

Subjective and quantitative assessment of patient fitness for cadaveric kidney transplantation: the "equity penalty".

BACKGROUND: Patient fitness at the time of organ allocation has an impact on graft survival equivalent to the effect of human leukocyte antigen (HLA) matching. The variation between institutions in assessment of fitness is not known, nor is the potential impact on mean graft survival of incorporating patient fitness into local adult cadaveric-kidney transplant-allocation algorithms. METHODS: Data from the Collaborative Transplant Study (CTS, 1985-2000) were reviewed. Quantitative criteria (QC) of patient fitness based on national transplant society guidelines were compared with subjective categorization (SC) of each patient on the current local transplant waiting list (n=109) determined by their supervising nephrologist. RESULTS: Five-year cadaveric graft survival was 70%, 61%, and 53% for good-, moderate-, and poor-risk patients in the CTS data set (n=102, 612), equivalent to half lives of 12.7, 9.8, and 8.7 years, respectively, with similar results from the local program. The distribution of local waiting-list patients into fitness categories A (good), B (moderate), C (poor), and D (unacceptable) was 51%:31%:13%:5% by SC and 25%:40%:27%:8% by QC. At one hospital, 61% (n=51) of patients were classified category A by SC, and falling to 16% by QC (P<.0001). Compared with preferential category A recipient allocation, an unrestricted allocation policy was estimated to sacrifice 1.5 years of overall program-mean graft survival. CONCLUSIONS: Use of QC may reduce the variation in subjective patient assessment seen between institutions. Any proposed changes in organ allocation methods should address the "equity versus efficiency" balance in an open fashion and predict the impact on the overall graft survival for the program by quantifying the "equity penalty."

Insulin resistance, dyslipidaemia, inflammation and endothelial function in nephrotic syndrome.

BACKGROUND: Nephrotic syndrome (NS) is associated with an increased risk of cardiovascular disease (CVD). We have shown previously that endothelial function, measured by post-ischaemic flow-mediated dilatation (FMD) of the brachial artery, is impaired in NS. In this study our aim was to assess the potential roles of insulin resistance, plasma non-esterified fatty acids (NEFAs) and inflammation in endothelial dysfunction in NS patients. METHODS: FMD was compared between NS patients (n=19) and controls (CS, n=19). Plasma glucose, insulin and NEFAs were measured. Insulin resistance was calculated using the Homeostasis Model Assessment (HOMA) score. C-reactive protein (CRP), interleukin-6 (IL-6), tumour necrosis factor alpha (TNFalpha) and fibrinogen were measured as markers of inflammation. RESULTS: FMD was significantly lower in the NS group (mean+/-standard error, NS 5.1+/-0.7%, CS 7.3+/-0.7%, P=0.02). Fasting insulin (NS 12.5+/-1.5 mU/l, CS 6.8+/-0.7 mU/l, P<0.01), fasting glucose (NS 5.3+/-0.2, CS 4.8+/-0.1, P=0.02) and the HOMA score (NS 3.0+/-0.4, CS 1.5+/-0.2, P=0.001) were significantly higher in NS. These differences persisted after adjusting for waist circumference. Of the inflammatory markers, only fibrinogen (P<0.01) and IL-6 (P=0.01) were significantly increased in NS. Despite significantly lower plasma NEFAs in NS, the NEFA:albumin ratio showed a non-significant trend to higher levels in NS (NS 10.7+/-0.1 micro mol/g, CS 8.7+/-0.1 micro mol/g, P=0.06). Within the NS group, multivariate backward regression analysis showed that NEFAs (P<0.01) and low-density lipoprotein (LDL) cholesterol (P=0.05) were significant negative independent predictors of FMD. CONCLUSION: Endothelial function in NS is inversely correlated with plasma concentrations of NEFAs and LDL cholesterol. Dyslipoproteinaemia and NEFAs probably contribute to the increased risk of CVD seen in NS. We also postulate that in NS, hypoalbuminaemia increases the delivery of NEFAs to endothelial cells thereby impairing the synthesis and release of nitric oxide.

Statin therapy improves brachial artery endothelial function in nephrotic syndrome.

BACKGROUND: Patients with nephrotic syndrome have impaired endothelial function probably related to dyslipidemia. This study evaluated the effects of statin therapy on dyslipidemia and endothelial function in patients with nephrotic syndrome. METHODS: A sequential, open-label study of the effects of statins on endothelial dysfunction in 10 nephrotic patients treated with an angiotensin-converting enzyme (ACE) inhibitor or angiotensin II (Ang II) receptor antagonist. Endothelial function was assessed at baseline, after 12 weeks of treatment with statins, and after an 8-week washout. Brachial artery endothelial function was measured as post-ischemic flow-mediated dilation (FMD) using ultrasonography. Endothelium-independent, glyceryl trinitrate-mediated vasodilation (GTNMD) also was measured. RESULTS: Serum lipids were significantly lower following statin: total cholesterol mean 8.2 +/- 0.4 (standard error) mmol/L versus 5.2 +/- 0.3 mmol/L, triglycerides 2.6 +/- 0.4 mmol/L versus 1.6 +/- 0.2 mmol/L, non-HDL-cholesterol 6.7 +/- 0.4 mmol/L versus 3.7 +/- 0.2 mmol/L (all P < 0.001). There was a trend to an increase in serum albumin (31.0 +/- 1.3 g/L vs. 33.8 +/- 1.5 g/L; P = 0.078) and FMD improved significantly following treatment (3.7 +/- 1.1% vs. 7.0 +/- 0.8%, P < 0.01). After washout, FMD deteriorated significantly to 3.5 +/- 1.4% (P < 0.05) versus week 12 FMD. GTNMD was unchanged. In multivariate regression, reduction in non-high-density lipoprotein (HDL)-cholesterol (beta - 0.736, P = 0.027) and increase in serum albumin (beta 0.723, P = 0.028), but not the on-treatment level of non-HDL-cholesterol, were significant independent predictors of improvement in FMD after adjusting for change in resting brachial artery diameter. Changes in serum lipoprotein and albumin concentrations off treatment were not associated with deterioration in FMD. CONCLUSION: Statin therapy significantly improves dyslipidemia and brachial artery endothelial function in patients with nephrotic syndrome. Improvement in brachial artery endothelial function may be in part related to a non-lipid effect of statins. The findings also suggest a role for dyslipidemia in endothelial dysfunction and the risk for cardiovascular disease in nephrotic syndrome.