Treating Diabetic Nephropathy: Unfinished Success Is Not Failure

[摘要] An irrefutable body of evidence from multiple well-powered clinical trials and numerous clinical studies in patients with type 1 and type 2 diabetes mellitus (DM) has demonstrated that inhibition of the renin-angiotensin system (RAS) retards the progression of diabetic nephropathy (1–11). The consistency of these clinical trial outcomes has resulted in guidelines from diabetes and renal societies to treat all patients with diabetes and diabetic nephropathy with drugs that inhibit the RAS (angiotensin-converting enzyme inhibitors [ACEI]) and/or angiotensin receptor antagonists (ARB) (12,13). The article by Ficociello et al. in this issue of CJASN documents the challenges and pitfalls of transporting these clinical trial and study results to a general population of patients (14). It is disheartening to read that, even in the most recent time of observation, 33% of patients with diabetic nephropathy did not receive any ACEI therapy despite current guideline recommendations. The transportability of clinical trial results is affected by differences between the study population and the general clinic population. By design, patients in clinical trials are judged to be compliant, do not have diseases other than diabetic nephropathy that could affect their kidney function, have clearly defined and accurately measured kidney function, and must meet many other inclusion and exclusion criteria. Certainly the general population of patients differs from those in a clinical trial, and those differences can affect the perceived efficacy of the intervention. The large number of patients in the observational study by Ficociello et al. with HgAIC levels far above those recommended by guidelines despite attendance in a dedicated diabetes clinic would suggest noncompliance. Interventions cannot benefit patients if they are not compliant or if the interventions are not properly implemented. Patients entering clinical trials are likely more compliant on average than a general clinic population. In addition, important areas to explore are the differences in health care delivery in a clinical trial that foster better compliance. The coordinators of clinical trials have to ensure timely visits and must educate patients, which may empower them to participate in their care more freely. Compliance with prescribed ACEI therapy is more carefully monitored, and there is consistency of ACEI therapy dosing in a trial, which is not necessarily reproduced in the clinic. This could have important effects on outcomes, as the Irbesartan Microalbuminuria II (IRMA 2) trial showed greater efficacy in patients randomized to the higher dose of irbesartan (11). Variation in compliance can be seen not only in the clinic but in clinical trials as well. Only recently has it become general knowledge that 50% of patients randomized to the ACEI, lisinopril, in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack (ALLHAT) trial either never received the drug or received it at such a low dose that it was unlikely to be renoprotective (15). This variation in patient compliance in ALLHAT raises serious doubt regarding reports derived from this study that question the renoprotective value of RAS blockade. These observations serve to emphasize the importance of accurate compliance data, whether in a clinical trial or in the clinic.

[学科分类] 泌尿医学

[关键词] Bone marrow necrosis;Sickle cell disease;Hyperhemolysis syndrome