Drug substitution in transplantation: a National Kidney Foundation White Paper.

Specific safeguards to guide the approval process and substitution practices for generic immunosuppressive agents are necessary for the effective delivery of patient care. Currently, the Food and Drug Administration (FDA) requires the demonstration of bioequivalence of generic drugs to innovator drugs in normal healthy subjects, a criterion that may be insufficient for critical-dose drugs. For generic equivalents of critical-dose drugs and for innovator critical-dose drugs, there should be a requirement for replicate studies measuring intrasubject variability and subject-treatment interactions to establish that bioequivalence holds true. Extensive testing of generic drugs in all target patient types is impractical and should not be required. However, when evidence suggests that the bioavailability of a critical-dose drug may vary substantially in certain subgroups, the FDA should require a demonstration of bioequivalence of generic versions to innovator products in these representative target populations. Changes in the approval process for generics should be accompanied by more consistent substitution practices. Pharmacists should notify the prescribing physician and patient whenever a critical-dose drug (generic or brand name) is dispensed in a different formulation from the one the patient has been taking. Therapeutic substitution for such drugs should not be made unless the prescribing physician has granted approval. The health care provider should consider instituting appropriate monitoring whenever patients are switched between generic formulations or between innovator drugs and generic formulations. Patients should be well informed about generic substitutes so that they can participate in treatment choices.

The 1989 morbidity and mortality meeting: how far have we come?

The Morbidity, Mortality, and Prescription of Dialysis Symposium was an international meeting held almost 9 years ago in Dallas, TX. The proceedings were subsequently published in the American Journal of Kidney Diseases. This article reviews key material from that meeting and evaluates what we have accomplished in the intervening years.

Living kidney donation: a survey of professional attitudes and practices.

Living donation is an option for meeting the needs of patients with end-stage renal disease. We surveyed kidney transplant professionals to understand their attitudes, opinions, and practices regarding living donation and to generate a rough estimate of the national potential for living related kidney donation. Although this sample of health practitioners expressed strong support for living donation, their actual professional practice does not necessarily reflect such support. Given the disparity between support and practice, we recommend that leaders in the kidney transplant community focus on several concrete objectives to optimize living donation: estimate the underlying potential for living donation; identify and implement best demonstrated practices for making the living donation request; explore and respond to the ethical issues that surround living donation; and address the needs of both donors and recipients.

The legislative and regulatory process in the end-stage renal disease (ESRD) program, 1973 through 1997.

Although hemodialysis began in the early 1960s, it did not begin to really grow until 1973, when the Federal government started to pay for end-stage renal disease (ESRD) treatment under Medicare. Since then, the Health Care Financing Administration (HCFA) has made a series of mistakes while maintaining this very successful program. This article traces the steps HCFA took, and the responses by the providers that produced the situation we have today. This program pays the lowest amount for hemodialysis of any industrialized nation, and most likely as a result has the highest mortality rate (23%) of any of the same countries. The problem as outlined is that HCFA attempted to ration by price while ignoring quality. This has been compounded by the providers finding more and more ways to reduce cost to continue to make a profit while not improving quality. The result is a program that could have been much better, and a patient population that has suffered.

Recommended clinical practices for maximizing peritoneal dialysis clearances.

Data from the Canada-U.S.A. (CANUSA) Study have recently confirmed a long-suspected linkage between total clearance and patient survival in peritoneal dialysis (PD). Recognizing that what we have historically accepted as adequate PD simply is not, the Ad Hoc Committee on Peritoneal Dialysis Adequacy met in January, 1996. This committee of invited experts was convened by Baxter Healthcare Corporation to prepare a consensus statement that provides clinical recommendations for achieving clearance guidelines for peritoneal dialysis. Through an analysis of 806 PD patients, the group concluded that adequate clearance delivered with PD can be achieved in almost all patients if the prescription is individualized according to the patient's body surface area, amount of residual renal function, and peritoneal membrane transport characteristics. Use of 2.5 L to 3.0 L fill volumes, the addition of an extra exchange, and giving automated peritoneal dialysis patients a "wet" day are all options to consider when increasing weekly creatinine clearance and KT/V. Rather than specify a single clearance or KT/V target, the recommended clinical practice is to provide the most dialysis that can be delivered to the individual patient, within the constraints of social and clinical circumstances, quality of life, life-style, and cost. The challenge to PD practitioners is to make prescription management an integral part of everyday patient management. This includes assessment of peritoneal membrane permeability, measurement of dialysis and residual renal clearance, and adjustment of the dialysis prescription when indicated.

Dialysis-related mortality in the United States.

BACKGROUND: In the United States, the gross mortality rate for patients undergoing dialysis in 1992 was 23.6% per year, higher than in any other industrialized country. This mortality rate has been rising slightly for the last 10 years. Wide variations in mortality rates exist among states and among dialysis centers, and smaller dialysis centers have higher mortality rates than larger ones. PURPOSE: To review the possible reasons for the high mortality rate associated with dialysis in the United States. SUMMARY: Differences in patient populations do not explain the variations in mortality rates. The incidence of new patients and the prevalence of older patients and patients with diabetes are higher in the United States than in other countries and are continuing to rise. However, these numbers are rising in other countries as well without a concomitant increase in their mortality rates. Black patients make up a disproportionate number of US dialysis patients, but they are less likely to die than white patients. US patients spend less time per week in dialysis than their European counterparts and use smaller dialyzers, resulting in lower clearance of solutes. CONCLUSION: Approximately two thirds of US patients receive inadequate dialysis. Nephrologists must examine their practices and their outcomes to improve the quality of care they give.

Predictors of the excessive mortality rates of dialysis patients in the United States.

It is now well recognized that the United States has the highest mortality rate for end-stage renal disease patients receiving dialysis among the industrialized nations. The possible causes of this almost 25% gross mortality rate (23.6% in 1992) are becoming clearer. After numerous investigations of the various possibilities, it is now evident that the causes are multifactorial. Basically, the US reimbursement for dialysis payment rate has been kept low (essentially no increase since 1973) by allowing inflation to advance and maintaining the actual costs. The industry has responded in a number of ways, some of which have proven harmful. For example, the reuse of dialyzers was probably reasonable and has not proven to be a problem: reductions in staff for older and sicker populations has probably been harmful to the patient's well being; and the shortening of dialysis treatments may have produced more problems than any other change. Essentially, as patients receive less dialysis they feel worse and lose their appetite, thus resulting in weight loss. Frequently dialysis is reduced further because of reduction in certain chemical markers, eg, blood urea nitrogen, that nephrologists use as clinical measurements. This results in a malnourished patient with a low serum albumin level. It is believed but not yet proven that an increase in the dialysis prescription, ie, more dialysis, can reverse this decline. Currently the United States faces the challenges of reducing its mortality rate for end-stage renal disease patients to compare with that of other industrial countries while remaining at the current reimbursement rate, which is less than half that of Germany and one quarter that of Japan.