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.