Open Access Open Badges Research article

Retained organic solutes, patient characteristics and all-cause and cardiovascular mortality in hemodialysis: results from the retained organic solutes and clinical outcomes (ROSCO) investigators

Michal L Melamed1*, Laura Plantinga2, Tariq Shafi3, Rulan Parekh4, Timothy W Meyer5, Thomas H Hostetter6, Josef Coresh37 and Neil R Powe8

Author Affiliations

1 Departments of Medicine and Epidemiology & Population Health, Albert Einstein College of Medicine, 1300 Morris Park Avenue – Ullmann 615, Bronx, NY 10461, USA

2 Department of Epidemiology, Emory University, Atlanta, GA, USA

3 Department of Medicine, Johns Hopkins School of Medicine, Baltimore, MD, USA

4 Departments of Medicine and Pediatrics, University of Toronto, Toronto, Canada

5 Department of Medicine, VA Palo Alto HCS and Stanford University, Palo Alto, CA, USA

6 Case Western University School of Medicine, Cleveland, OH, USA

7 Departments of Epidemiology and Biostatistics, Johns Hopkins Bloomberg School of Public Health, Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins University, Baltimore, MD, USA

8 Department of Medicine, University of California and Center for Vulnerable Populations, San Francisco General Hospital, San Francisco, CA, USA

For all author emails, please log on.

BMC Nephrology 2013, 14:134  doi:10.1186/1471-2369-14-134

Published: 27 June 2013



Multiple solutes are retained in uremia, but it is currently unclear which solutes are toxic. Small studies suggest that protein-bound solutes, such as p-cresol sulfate and indoxyl sulfate and intracellular solutes, such as methylamine (MMA) and dimethylamine (DMA), may be toxic. Our objective was to test whether elevated levels of these solutes were associated with mortality.


We conducted a prospective cohort study in 521 U.S. incident hemodialysis patients to evaluate associations between these solutes and all-cause and cardiovascular mortality. P-cresol sulfate, indoxyl sulfate, MMA and DMA levels were measured from frozen plasma samples obtained 2 to 6 months after initiation of dialysis. Mortality data was available through 2004 using the National Death Index.


Elevated (greater than the population median) p-cresol sulfate, MMA or DMA levels were not associated with all-cause or cardiovascular mortality. Elevated indoxyl sulfate levels were associated with all-cause mortality but not cardiovascular mortality (hazard ratio 1.30 (95% confidence interval 1.01, 1.69) p-value 0.043).


In this cohort of 521 incident hemodialysis patients, only elevated indoxyl sulfate levels were associated with all-cause mortality. Further research is needed to identify causes of the toxicity of uremia to provide better care for patients with kidney disease.

All-cause Mortality; Cardiovascular Mortality; Dialysis Outcomes; Indoxyl Sulfate; P-cresol Sulfate; Uremic Solutes