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The term "reverse epidemiology" has been proposed to address the apparent different relationship between numerous risk factors and outcomes among dialysis patients: thus, obesity, hypertension, high cholesterol, and elevated creatinine all appear to be associated with decreased risk. Since this is contrary to the general findings in otherwise healthy populations, some kind of "reversal" has been suggested, that would be contrary to classical epidemiology. The authors describe several faults to this conception. The rules of epidemiology have not been reversed in dialysis patients. In fact, the complexity of the population implies a greater need for attention to the distinction between association and causation and the importance of confounding and bias. In particular existing subclinical and clinical disease which is very common among dialysis patients can change associations so drastically that they are dominated by different causal pathways than those seen in the general population. For example, lower cholesterol is a better marker of poor health than of a healthy diet and thus is associated with different outcomes. To the extent the term reverse epidemiology implies either epidemiology or biology is different in dialysis patients it can be misleading and detrimental. The differences between risk factors in end-stage renal disease (ESRD) and other individuals are surely important, but can themselves be the basis of excellent epidemiology, applied with the classic rules developed for this discipline with the goal of uncovering causal association and hypotheses to be tested in clinical trials.

and also met with several Minntech executives. During this period, the authors ex- plained their analytical methods and results to Minntech, provided statistical output to Minntech, and considered Minntech’s disagreements with the research. As part of a prepublication review pro- cess, a draft version of the study manuscript

Traditional risk factors for atherosclerotic cardiovascular disease (CVD) do not adequately explain the considerable increase in cardiovascular mortality observed among patients with end-stage renal disease (ESRD): these patients experience mortality rates 10–100 times those without ESRD. Disorders of mineral metabolism, including abnormalities in calcium, phosphorus, parathyroid hormone, and vitamin D, represent cardiovascular risk factors unique to the ESRD population. These disturbances manifest clinically through the promotion of extraskeletal calcification and disorders of bone remodeling, two processes which appear to share a common pathogenesis. This article presents evidence describing the impact of calcification-induced arterial stiffness on cardiovascular outcomes of patients with ESRD, along with data relating altered mineral metabolism to all-cause and cardiovascular mortality. Specific management recommendations include 1) early intervention to prevent the development of overt secondary hyperparathyroidism, 2) a more judicious strategy for vitamin D therapy, and 3) a thoughtful approach to the use of calcium-containing phosphate binders, taking into account the underlying bone remodeling disorder and the presence or absence of extraskeletal calcium accumulation.

The term "reverse epidemiology" has been proposed to address the apparent different relationship between numerous risk factors and outcomes among dialysis patients: thus, obesity, hypertension, high cholesterol, and elevated creatinine all appear to be associated with decreased risk. Since this is contrary to the general findings in otherwise healthy populations, some kind of "reversal" has been suggested, that would be contrary to classical epidemiology. The authors describe several faults to this conception. The rules of epidemiology have not been reversed in dialysis patients. In fact, the complexity of the population implies a greater need for attention to the distinction between association and causation and the importance of confounding and bias. In particular existing subclinical and clinical disease which is very common among dialysis patients can change associations so drastically that they are dominated by different causal pathways than those seen in the general population. For example, lower cholesterol is a better marker of poor health than of a healthy diet and thus is associated with different outcomes. To the extent the term reverse epidemiology implies either epidemiology or biology is different in dialysis patients it can be misleading and detrimental. The differences between risk factors in end-stage renal disease (ESRD) and other individuals are surely important, but can themselves be the basis of excellent epidemiology, applied with the classic rules developed for this discipline with the goal of uncovering causal association and hypotheses to be tested in clinical trials.

Traditional risk factors for atherosclerotic cardiovascular disease (CVD) do not adequately explain the considerable increase in cardiovascular mortality observed among patients with end-stage renal disease (ESRD): these patients experience mortality rates 10-100 times those without ESRD. Disorders of mineral metabolism, including abnormalities in calcium, phosphorus, parathyroid hormone, and vitamin D, represent cardiovascular risk factors unique to the ESRD population. These disturbances manifest clinically through the promotion of extraskeletal calcification and disorders of bone remodeling, two processes which appear to share a common pathogenesis. This article presents evidence describing the impact of calcification-induced arterial stiffness on cardiovascular outcomes of patients with ESRD, along with data relating altered mineral metabolism to all-cause and cardiovascular mortality. Specific management recommendations include 1) early intervention to prevent the development of overt secondary hyperparathyroidism, 2) a more judicious strategy for vitamin D therapy, and 3) a thoughtful approach to the use of calcium-containing phosphate binders, taking into account the underlying bone remodeling disorder and the presence or absence of extraskeletal calcium accumulation.

The renal community owes Dr. Frank Gotch a great debt for the contributions that he has made to clarify the relationship between urea clearance and the dose of dialysis. With John Sargent he developed the mathematical approach to hemodialysis (1). In his seminal publication he re-analyzed data of the National Cooperative Dialysis Study to establish the association between the theoretically derived Kt/V for urea and clinical outcomes (2). Although diffusion equations are well understood and are used in many fields of science, Dr. Gotch’s persistent and tireless efforts to identify and quantitate the specific aspects of this process in dialysis through formal kinetic modeling, yielding additionally the protein catabolic rate (PCR) (3), have been extremely valuable to both patients and clinicians alike. The continuing measurement of Kt/ Vurea in every dialysis unit is a lasting tribute to Dr. Gotch’s contributions. Accurate measurement of the dose of dialysis is important in part because of its relationship to patient outcomes and to the cost of dialysis. Further, the concepts underlying the dose of episodic hemodialysis, pioneered by Dr. Gotch, are of practical importance in understanding the role of residual renal function and in quantitateing the dose of continuous dialytic procedures. Kt/V has been found to be one of the key modifiable components of the practice of hemodialysis.