Levels of albuminuria and risk of developing macroalbuminuria in type 2 diabetes: historical cohort study

Abstract

Although increased urinary albumin excretion may increase the risk of adverse renal outcomes in patients with diabetes, it remains unclear whether microalbuminuria is associated with a higher incidence of macroalbuminuria in the absence of non-diabetic kidney events that frequently develop during the long-term course of type 2 diabetes. This historical cohort study included patients with type 2 diabetes, spot urine albumin:creatinine ratio (ACR) <300 mg/gCr and normal serum creatinine concentrations treated between August 1988 and April 2015. Patients with any evidence suggesting non-diabetic kidney diseases at baseline were excluded. Over a median follow-up of 50 months, 70 of the 1760 included patients developed macroalbuminuria. Twenty-one of these patients were diagnosed with non-diabetic renal events. The five-year cumulative incidence of macroalbuminuria in patients with ACRs of 0–7.5 mg/gCr, 7.5–30 mg/gCr, 30–150 mg/gCr, and 150–300 mg/gCr were 0%, 0.53%, 3.5%, and 36.0%, respectively, with significant differences between each pair of ACR categories. In type 2 diabetes, higher urinary ACR, even within a level of normoalbuminuria, was associated with a greater incidence of macroalbuminuria when non-diabetic renal events were excluded. These results conflict with findings suggesting that microalbuminuria is a poor indicator for the progression of diabetic nephropathy.

Tolvaptan alleviates excessive fluid retention of nephrotic diabetic renal failure unresponsive to furosemide

“…Since there was no effective treatment for the massive fluid overload (except for immediate initiation of renal replacement therapy), oral tolvaptan therapy (30 mg in one patient, 15 mg in 10 patients, and 7.5 mg in three patients) was initiated, while body weight, urinary volume, estimated glomerular filtration rate (eGFR), serum sodium and potassium concentration, free water clearance, and urinary sodium and protein excretions were closely monitored. All patient management protocols conformed to routine diabetic nephropathy patient diagnostic and management regimens covered by the Universal Health Insurance System of Japan, and were performed in accordance with the Ethical Guidelines for Medical and Health Research Involving Human Subjects, Japan.…”

“…The progression of nephropathy in type 2 diabetes is slow during the incipient stage . However, upon development of overt nephropathy, it accelerates, resulting in relentless deterioration .…”

Methionine sulfoxides in serum proteins as potential clinical biomarkers of oxidative stress

“…Type 2 diabetes was diagnosed in individuals who were confirmed to be insulin independent according to the criteria of the Japan Diabetes Society (patients with anti-glutamic acid decarboxylase autoantibody >1.5 U/ml or serum C-peptide <0.5 ng/ml were excluded)43. Chronic renal failure was diagnosed after confirming sustained elevation of serum creatinine levels for at least 6 months4445.…”

“…Type 2 diabetic patients provided an additional serum sample at the time of scheduled blood sampling on the last morning of 72-h CGM recording using the CGMS system GOLD (Medtronic Minimed Inc. Northridge, CA)4647. They also received our routine systemic evaluation protocols for diabetic patients covered by universal health coverage system in Japan4348, which include laboratory tests, such as urinalysis, a complete blood count, serum biochemical analysis for more than 15 items, anti-glutamic acid decarboxylase antibody, glycated albumin, HbA1c, and fasting serum insulin. Blood was withdrawn from an antecubital vein into vacutainers containing pro-coagulant and allowed to clot at room temperature for the indicated time, before centrifugation at 2,000 ×  g for 15 min at room temperature.…”

Ambulatory blood pressure in the dash diet trial: Effects of race and albuminuria

“…For example, Jacobs et al previously estimated that compared to a daily UAE of 2.0 mg, UAE of 5.5, 16.3, and 20.3 mg were associated with relative risks for all‐cause mortality of 1.08, 1.46, and 2.34, respectively. In a prospective cohort of 1760 patients with type 2 diabetes and normal kidney function, Chida et al found that higher, compared to lower, levels of albuminuria within thresholds of normal (albumin‐to‐creatinine ratio 7.5‐30 mg/g vs <7.5 mg/g) was associated with progression to macroalbuminuria and was predictive of progression to diabetic nephropathy. With low‐grade albuminuria being reflective of subclinical CKD and endothelial dysfunction, it is plausible that ambulatory BP response to DASH would differ within this subgroup.…”