composite endpoint of ESKD, doubling of serum creatinine, CV death or renal death. The trial was stopped nearly two years early by the independent committee due to eicacy and safety. Primary composite outcomes are shown in Figure 2. Highlights of the trial include the following:40 Canagliflozin reduced the risk of the primary outcome of ESKD, doubling of serum creatinine, or renal or CV mortality by 30% (HR 0.70, CI 95%, 0.59- 0.82, P Diabetic nephropathy: Prevention and treatment Principal discussant: Hans-Henrik Parving Steno Diabetes Center, Gentofte, Denmark tensive regimen was continued. Within 3 months from the initiation of antihypertensive treatment, her blood pressure fell to 108/60 mm Hg, the GFR dropped from 91 to 69 mL/min, and the albuminuria declined to 423 g/min (609 m/24 h). During the following 18 years, GFR measured twice yearly ranged between 50 and 70 mL/min; at the end of follow-up 2 years ago, the value was 61 mL/min, giving a sustained rate of decline in GFR during the total observation period of 0.4 mL/min/ year. With few exceptions, albuminuria stayed below 500 g/ min (720 mg/24 h), and the mean blood pressure during the whole treatment period was 125/77 mm Hg. Glycosylated hemoglobin (HbA1c) ranged between 7.7% and 10.3%, with a mean of 9.0% during the observation period. Three years ago, because of a progressive lack of hypoglycemic awareness, she experienced several episodes of severe hypoglycemia. TreatCASE PRESENTATION ment with metoprolol was stopped and angiotensin-converting enzyme inhibition was started. Shortly after, the patient devel- A 19-year-old female was admitted to the Steno Diabetes oped an irritative cough that required cessation of this medica- Center 24 years ago because of poorly controlled type 1 diabetes, tion. She was then given hydralazine, furosemide (as mentioned which had been diagnosed 6 years earlier. The patient was earlier), and a calcium antagonist. The systolic blood pressure treated with insulin twice daily and a diabetic diet. A simplex rose (to 156/70 mm Hg), as did the albuminuria (2330 g/min retinopathy was diagnosed, and she had persistent albuminuria or 3355 mg/24 h), while the GFR remained unchanged (60 mL/ ranging between 500 and 650 g/min (720 and 936 mg/24 h). Her blood pressure was 120/86 mm Hg and glomerular filtration min). She was given the angiotensin II type-1 receptor blocker losartan when it became available 2 years ago; treatment in- rate (GFR: 51Cr-EDTA plasma clearance) was 119 mL/min. The duced a significant decline in blood pressure, a decrease by one- urine sediment was normal and a urine culture was negative. half of the albuminuria, and a decline in GFR to 48 mL/min. Because of the short duration of her diabetes, a renal biopsy During the course of her renal disease, she became pregnant 19 was performed; it showed diffuse diabetic glomerulopathy. During the following 3 years, the albuminuria increased pro- years ago and delivered a healthy child after an uncomplicated pregnancy. Three years ago, screening demonstrated increased gressively, reaching as high as 1815 g/min (2614 mg/24 h). Her blood pressure rose to a final level of 136/105 mm Hg and serum calcium and elevated parathyroid hormone (PTH). SurGFR declined to 91 mL/min after 3 years of follow-up without gical exploration revealed an adenoma (208 mg) in the parathyroid gland. Following surgery, her serum calcium became nor- any antihypertensive treatment. The rate of decline in GFR mal. The patient still has a simplex retinopathy with normal averaged 10.3 ml/min/year, mean blood pressure during the 3 visual acuity. years of observation was 126/90 mm Hg, and average albuminuria was 1021 g/min (1470 mg/24 h). After three years of follow-up, treatment was initiated with a selective beta-blocker, metoprolol, 200 mg daily; furosemide, DISCUSSION 120 to 240 mg twice daily; and hydralazine, 25 (and then 50) Dr. Hans-Henrik Parving (Professor of Medicine, mg twice daily. Apart from minor adjustments, this antihyper- Chief Physician, Steno Diabetes Center, Copenhagen, Denmark): The clinical syndrome termed diabetic nephropathy is characterized by persistent albuminuria, blood The Nephrology Forum is funded in part by grants from Amgen, pressure elevation, a relentless decline in GFR, and a Incorporated; Merck & Co., Incorporated; Dialysis Clinic, Incorporated; and Bristol-Myers Squibb Company. high risk of cardiovascular morbidity and mortality [1]. Diabetic nephropathy has become the leading cause Key words: type 1 diabetes, type 2 diabetes, glycemic control, lowprotein diet, lipid-lowering drugs, antihypertensive drugs, albuminuria, (25% to 42% of patients) of end-stage renal disease hypertension, ESRD (ESRD) in Europe, Japan, and the United States [1]. 2001 by the International Society of Nephrology Unfortunately, the proportion of patients with ESRD 2041 CORE Metadata, citation and similar papers at core.ac.uk Provided by Elsevier - Publisher Connector 2042 Nephrology Forum: Diabetic nephropathy suffering from diabetes, particularly type 2, is anticipated to elevated blood pressure exists in diabetes [20]. The to rise considerably because the number of diabetic pa- following abnormalities might contribute to the increased tients in the world is