Risk for ESRD in Type 1 Diabetes Remains High Despite Renoprotection

Abstract

Historically, patients with type 1 diabetes and macroalbuminuria had high competing risks: cardiovascular death or renal failure. Here, we assessed these risks in patients receiving therapies implemented during the last 30 years. Between 1991 and 2004, we enrolled 423 white patients with type 1 diabetes who developed macroalbuminuria (albumin excretion rate, Ն300 g/min). With follow-up for 98% through 2008, ESRD developed in 172 patients (incidence rate, 5.8/100 person-years), and 29 died without ESRD (mortality rate, 1/100 person-years). The majority of these outcomes occurred between ages 36 and 52 years with durations of diabetes of 21 to 37 years. The 15-year cumulative risks were 52% for ESRD and 11% for pre-ESRD death. During the 15 years of follow-up, the use of renoprotective treatment increased from 56 to 82%, and BP and lipid levels improved significantly; however, the risks for both ESRD and pre-ESRD death did not change over the years analyzed. There were 70 post-ESRD deaths, and the mortality rate was very similar during the 1990s and the 2000s (11/100 person-years versus 12/100 person-years, respectively). Mortality was low in patients who received a pre-emptive kidney transplant (1/100 person-years), although these patients did not differ from dialyzed patients with regard to predialysis eGFR, sex, age at onset of ESRD, or duration of diabetes. In conclusion, despite the widespread adoption of renoprotective treatment, patients with type 1 diabetes and macroalbuminuria remain at high risk for ESRD, suggesting that more effective therapies are desperately needed.

Results of Pancreas Transplantation Alone with Special Attention to Native Kidney Function and Proteinuria in Type 1 Diabetes Patients

“…The effects of PTA on the reduction of proteinuria may be of particular relevance. Notably, very recent data show that the risk of end-stage renal disease remains high and unchanged despite renoprotective treatments [33]. This finding may suggest the need for new therapies in diabetic patients with overt diabetic nephropathy.…”

Blood Kidney Injury Molecule-1 Is a Biomarker of Acute and Chronic Kidney Injury and Predicts Progression to ESRD in Type I Diabetes

“…15 Of 423 patients participating in the cohort, a random subgroup of 124 patients with a sufficient amount of baseline serum was selected for the current study. The baseline characteristics of the selected patients are shown in Supplemental Table 4.…”

“…Analyses shown in D and E were performed in 107 patients with type 1 diabetes, proteinuria, and CKD stages 1-3 at baseline. More clinical information of these patients is provided in Supplemental Table 4 and can be found in Rosolowsky et al 15 (F) Western blot depicting 90-kD band of urinary KIM-1 in a patient with AKI (lane 2) and plasma KIM-1 in patients with AKI (lanes 4 and 5), and CKD (lane 6). Urine (lane 1) and plasma (lane 3) from healthy volunteers were also included for comparision.…”

“…During the follow-up period, 24 of the 107 patients who had stage 1-3 CKD at baseline developed ESRD. 15 To further examine the association of baseline serum KIM-1 with risk of ESRD, Kaplan-Meier survival analysis was performed. As shown in Figure 3E, after 12.5 years of follow-up, only 20% of patients with serum levels of KIM-1 below the median (97 pg/ml) progressed to ESRD compared with 63% of patients with baseline KIM-1 above the median (P,0.01).…”

Cardiac Autonomic Neuropathy and Early Progressive Renal Decline in Patients with Nonmacroalbuminuric Type 1 Diabetes

“…Although rates of complications appear to have declined substantially over the past 2 decades, such improvements may not apply to the rates of ESRD (3). Furthermore, despite advances aimed at improving glycemic control and inhibiting deleterious neurohormonal pathways, such as the renin-angiotensin-aldosterone system (RAAS), evidence from population databases and clinical trials imply that the incidence of DN has been postponed but not outright prevented (4)(5)(6)(7). Finally, the overall prevalence of DN continues to increase in proportion to the rising prevalence of diabetes (3,8).…”