Effect of Renin-angiotensin-system Blockade on Urinary Free Light Chains in Patients With Type 2 Diabetes Mellitus

Effect of Renin-angiotensin-system Blockade on Urinary Free Light Chains in Patients With Type 2 Diabetes Mellitus

The purpose of this study is to study the effect of blocking the renin angiotensin system on urinary free light chain excretion as compared to urine microalbumin creatinine ratio in subjects with type 2 diabetes. The long term goal is to assess urinary free-light chains as a biomarker of earlier detection of kidney function impairment in subjects with diabetes mellitus.

Free light chains (FLCs) are low-molecular-mass molecules (kappa and lambda light chains), which are by-products of normal immunoglobulin synthesis and are normally excreted through the kidneys. Presence of light chains in the urine is a marker of tubular dysfunction. In patients with impaired kidney function, serum concentrations and urinary excretion of polyclonal FLCs have been noted to be increased. Increased excretion of FLCs and other low-molecular weight proteins [cystatin C, NGAL] in the urine may contribute to progression of chronic kidney disease. Higher Cystatin C has been demonstrated to be related to development of albuminuria. Neutrophil gelatinase-associated lipcalin (NGAL) excretion in the urine is a marker of tubular injury in the kidney and has been shown to be elevated in subjects with type 1 and 2 diabetes mellitus (DM). Angiotensin-converting enzyme inhibitors (Ace Inh) and angiotensin II receptor blockers (ARB) class of drugs are renoprotective in nature and are the first line therapy for treatment of diabetic nephropathy. There is no longitudinal data evaluating the effect of Ace Inh and ARB class of drugs on urinary FLCs (UFLCs).

Our hypothesis is that UFLCs are increased in patients with DM with and without kidney disease and that treatment with Ace Inh and/or ARB will decrease UFLCs in these patients. Additionally, we will explore the change in other low molecular weight proteins [cystatin C, and NGAL] in response to treatment with Ace Inh and ARB.

Inclusion Criteria:

• Type 2 Diabetes
• Hypertension
• Estimated glomerular filtration rate (eGFR) > 30 ml/min
• Use of Ace Inh and ARB for control of blood pressure who are willing to be placed on alternate drug(s) in the washout period for blood pressure control

Exclusion Criteria:

• Pregnancy
• Patients with chronic kidney disease stage with eGFR < 30 ml/min (CKD stage IV and V)
• Nephrotic range proteinuria (urinary protein > 3.5 gm/day)
• History or renal transplantation
• History of multiple myeloma
• Known history of hypersensitivity reaction or intolerability to Ace Inh or ARB.