Predicting 6-month mortality risk of patients commencing dialysis treatment for end-stage kidney disease.

BACKGROUND: There is evidence that end-stage kidney disease patients who are older or with more comorbidity may have a poor trade-off between benefits of dialysis and potential harms. We aimed to develop a tool for predicting patient mortality in the early stages of receiving dialysis. METHODS: In 23 658 patients aged 15+ years commencing dialysis between 2000 and 2009 in Australia and New Zealand a point score tool was developed to predict 6-month mortality based on a logistic regression analysis of factors available at dialysis initiation. Temporal validation used 2009-11 data from Australia and New Zealand. External validation used the UK Renal Registry. RESULTS: Within 6 months of commencing dialysis 6.1% of patients had died. A small group (4.7%) of patients had a high predicted mortality risk (>20%), as predicted by the point score tool. Predictive variables were: older age, underweight, chronic lung disease, coronary artery disease, peripheral vascular disease, cerebrovascular disease (particularly for patients <60 years of age), late referral to nephrologist care and underlying cause of renal disease. The new point score tool outperformed existing models, and had an area under the receiver operating characteristic curve of 0.755 on temporal validation with acceptable calibration and 0.713 on external validation with poor calibration. CONCLUSION: Our point score tool for predicting 6-month mortality in patients at dialysis commencement has sufficient prognostic accuracy to use in Australia and New Zealand for prognosis and identification of high risk patients who may be given appropriate supportive care. Use in other countries requires further study.

Residual proteinuria and eGFR predict progression of renal impairment within 2 years in type 2 diabetic patients with nephropathy who are receiving optimal treatment with angiotensin receptor blockers.

AIM: Proteinuria and estimated glomerular filtration rate (eGFR) predict progression of renal impairment in type 2 diabetic nephropathy (DN) but are they still predictive when these patients are treated with angiotensin receptor blockers (ARB)? We investigated whether residual (after ≥3 months of ARB treatment) urinary protein/creatinine ratio (rPCR) or urinary albumin/creatinine ratio (rACR) and residual eGFR (reGFR), predict subsequent progression. METHODS: One thousand, two hundred and forty-five patients with type 2 DN from two international multi-center studies were analysed. Cross classification of rPCR, rACR with reGFR (rPCR: <1000, 1000-<2000 and ≥2000 mg/g; rACR: <666.7, 666.7-<1333.3 and ≥1333.3 mg/g; reGFR: 15-29, 30-44 and 45-59 mL/min per 1.73 m2). Progression of renal disease exhibited as: end stage renal failure, doubling of serum creatinine, or serum creatinine ≥6 mg/dL. RESULTS: Increasing rPCR or rACR, and decreasing reGFR were strongly associated with increasing risk of renal disease progression, with no evidence of interaction between rPCR and reGFR, or rACR and reGFR. The estimated 24-month risk was low (<8%) for patients with rPCR <1000 mg/g regardless of reGFR, for patients with reGFR ≥45 mL/min per 1.73 m2 regardless of rPCR, or with rPCR between 1000-<2000 mg/g and reGFR ≥30 mL/min per 1.73 m2 . However, the risk rose steeply (to 39.4%) for reGFR <30 mL/min per 1.73 m2 and rPCR ≥2000 mg/g. CONCLUSION: Despite DN patients being treated with ARB, renal disease progression risk over 2 years increases with increasing proteinuria, albuminuria and decreasing eGFR. Recognition of these risk factors' impact is important in patient management and future clinical trial design.

Sulodexide fails to demonstrate renoprotection in overt type 2 diabetic nephropathy.

Sulodexide, a mixture of naturally occurring glycosaminoglycan polysaccharide components, has been reported to reduce albuminuria in patients with diabetes, but it is unknown whether it is renoprotective. This study reports the results from the randomized, double-blind, placebo-controlled, sulodexide macroalbuminuria (Sun-MACRO) trial, which evaluated the renoprotective effects of sulodexide in patients with type 2 diabetes, renal impairment, and significant proteinuria (>900 mg/d) already receiving maximal therapy with angiotensin II receptor blockers. The primary end point was a composite of a doubling of baseline serum creatinine, development of ESRD, or serum creatinine ≥6.0 mg/dl. We planned to enroll 2240 patients over approximately 24 months but terminated the study after enrolling 1248 patients. After 1029 person-years of follow-up, we did not detect any significant differences between sulodexide and placebo; the primary composite end point occurred in 26 and 30 patients in the sulodexide and placebo groups, respectively. Side effect profiles were similar for both groups. In conclusion, these data do not suggest a renoprotective benefit of sulodexide in patients with type 2 diabetes, renal impairment, and macroalbuminuria.

Proteinuria in type 2 diabetic patients with renal impairment: the changing face of diabetic nephropathy.

Type 2 diabetic nephropathy (type 2 DN) patients traditionally develop significant proteinuria prior to the development of renal impairment. However, this clinical paradigm, based on observations prior to the widespread usage of angiotensin-converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARB), has recently been questioned. 2,303 patients enrolled in the Sulodexide Overt Nephropathy Study (OVERT) were analyzed. Prior therapy with ACEi and/or ARB at the time of screening was recorded in 951 patients. 22% of patients had significant renal impairment with a PCR at screening of <500 mg/g. Therapy with ACEi and/or ARB at the time of screening was recorded in 94%, where prior medication data was available. In patients with type 2 DN and advanced renal impairment, levels of proteinuria below that which traditionally defines overt diabetic nephropathy, are found in more than one fifth of patients. We suggest that the high prevalence of ACEi and ARB usage in patients with type 2 DN may be effecting the traditional clinical paradigm of type 2 DN.