Evaluation of Serum Creatinine and Cockcroft-Gault Estimated GFR as an Early Biomarker of Renal Impairment in Patients with Type 2 Diabetes Mellitus

Abstract Aims/hypothesis In previous work, we reported the HR for the risk (95% CI) of the secondary kidney composite endpoint (time to first event of doubling of serum creatinine from baseline, renal dialysis/transplant or renal death) with ertugliflozin compared with placebo as 0.81 (0.63, 1.04). The effect of ertugliflozin on exploratory kidney-related outcomes was evaluated using data from the eValuation of ERTugliflozin effIcacy and Safety CardioVascular outcomes (VERTIS CV) trial (NCT01986881). Methods Individuals with type 2 diabetes mellitus and established atherosclerotic CVD were randomised to receive ertugliflozin 5 mg or 15 mg (observations from both doses were pooled), or matching placebo, added on to existing treatment. The kidney composite outcome in VERTIS CV (reported previously) was time to first event of doubling of serum creatinine from baseline, renal dialysis/transplant or renal death. The pre-specified exploratory composite outcome replaced doubling of serum creatinine with sustained 40% decrease from baseline in eGFR. In addition, the impact of ertugliflozin on urinary albumin/creatinine ratio (UACR) and eGFR over time was assessed. Results A total of 8246 individuals were randomised and followed for a mean of 3.5 years. The exploratory kidney composite outcome of sustained 40% reduction from baseline in eGFR, chronic kidney dialysis/transplant or renal death occurred at a lower event rate (events per 1000 person-years) in the ertugliflozin group than with the placebo group (6.0 vs 9.0); the HR (95% CI) was 0.66 (0.50, 0.88). At 60 months, in the ertugliflozin group, placebo-corrected changes from baseline (95% CIs) in UACR and eGFR were −16.2% (−23.9, −7.6) and 2.6 ml min−1 [1.73 m]−2 (1.5, 3.6), respectively. Ertugliflozin was associated with a consistent decrease in UACR and attenuation of eGFR decline across subgroups, with a suggested larger effect observed in the macroalbuminuria and Kidney Disease: Improving Global Outcomes in Chronic Kidney Disease (KDIGO CKD) high/very high-risk subgroups. Conclusions/interpretation Among individuals with type 2 diabetes and atherosclerotic CVD, ertugliflozin reduced the risk for the pre-specified exploratory composite renal endpoint and was associated with preservation of eGFR and reduced UACR. Trial registration ClinicalTrials.gov NCT01986881 Graphical abstract

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SP453ANKLE-BRACHIAL INDEX IS ASSOCIATED WITH RENAL IMPAIRMENT IN PATIENTS WITH ARTERIAL HYPERTENSION AND TYPE 2 DIABETES MELLITUS

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfx149.sp453 ◽

2017 ◽

Vol 32 (suppl_3) ◽

pp. iii275-iii275

Author(s):

Elena Troitskaya ◽

Ekaterina Starostina ◽

Zhanna Kobalava

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Renal Impairment ◽

Arterial Hypertension

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A STUDY OF SERUM URIC ACID LEVELS IN TYPE 2 DIABETES MELLITUS CASES AND ITS COMPARISON WITH THE SERUM CREATININE LEVELS

10.36106/paripex/0302859 ◽

2021 ◽

pp. 20-22

Author(s):

Shajahan Shajahan ◽

Koneru Sri Lahari ◽

P. Kiranmai

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Uric Acid ◽

Serum Creatinine ◽

Serum Uric Acid ◽

Fasting Blood Glucose ◽

Control Group ◽

P Value

BACKGROUND:Type 2 Diabetes Mellitus is a major non-communicable disease resulting from insulin resistance and is associated with cardiovascular,neurological and renal complications.Recent studies show association of hyperuricemia and Diabetes Mellitus.Uric acid increases oxidative stress that leads to vascular dysfunction and high intra glomerular pressure leading to renal complications.High serum creatinine is an indicator of renal compromise. OBJECTIVES: To evaluate serum uric acid and serum creatinine levels in type 2 diabetes mellitus patients and to find association between them. METHODOLOGY: The study was conducted in Osmania general hospital. Fifty cases of established Type 2 Diabetes Mellitus formed the study group and 50 normal healthy individuals formed the control group. Serum uric acid, Fasting Blood Glucose (FBS) and serum creatinine were estimated by colorimetric enzymatic methods on Beckman coulter AU5800.Mean values were compared in cases and controls using student t- test.Study group was further studied under 2 subgroups with serum Uric acid < 7 mg/dl and ≥7 mg/dl.In these 2 subgroups the association of Serum uric acid with FBS and creatinine was analysed statistically. RESULTS: Serum uric acid were found high in cases(7.63+/- 3.36)as compared to controls(4.48+/- 1.09) p value < 0.001.Serum creatinine were also high in cases(1.59+/- 1.39 )as compared to controls ( 0.87+/- 0.29) p value <0.005.Study subgroup with serum uric acid ≥7 mg/dl was associated with high creatinine and high fasting blood sugar levels when compared to subgroup with serum uric acid <7 mg/dl. CONCLUSION: Our study showed increased serum uric acid and serum creatinine levels in cases when compared to controls.There was significant association between high serum uric acid and high creatinine levels in cases.Therefore,it is important to measure serum uric acid and serum creatinine levels in diabetics for early detection of renal pathology.

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Abstract 11267: LX4211, a Dual Inhibitor of Sodium-Glucose Cotransporters 1 and 2, Reduces Systolic Blood Pressure in Patients With Type 2 Diabetes Mellitus and Moderate to Severe Renal Impairment

Circulation ◽

10.1161/circ.130.suppl_2.11267 ◽

2014 ◽

Vol 130 (suppl_2) ◽

Author(s):

Pablo Lapuerta ◽

Paul Strumph ◽

Philip Banks ◽

Ikenna Ogbaa ◽

Brian Zambrowicz ◽

...

Keyword(s):

Diabetes Mellitus ◽

Blood Pressure ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Renal Impairment ◽

Systolic Blood Pressure ◽

Severe Renal Impairment ◽

Postprandial Glucose ◽

Dual Inhibitor

Introduction: Selective sodium-glucose cotransporter 2 (SGLT2) inhibitors target only the kidney, and they have reduced efficacy when patients with type 2 diabetes mellitus (T2DM) have renal impairment (RI). LX4211 blocks sodium and glucose absorption in the gastrointestinal tract by inhibition of SGLT1, and it enhances urinary sodium and glucose excretion in the urine through inhibition of SGLT2. The dual SGLT1/2 action of LX4211 was anticipated to reduce systolic blood pressure (SBP) in addition to improving glucose control in the setting of RI. Methods: This analysis explored the effect of LX4211 on SBP in a clinical trial of patients with T2DM and moderate to severe RI. Patients (N=31) were randomly assigned to be treated with LX4211 (400 mg, N=16) or placebo (N=15) qd for 7 consecutive days. Postprandial glucose levels after a standard high glucose meal served as the primary measure of pharmacodynamic activity. Baseline and Day 8 trough SBP measures were each an average of 3 seated assessments. Results: Mean baseline characteristics included age 66.4 years, estimated glomerular filtration rate (eGFR) 43.4 mL/min/1.73 m 2 , and SBP 130.9 mmHg. Postprandial glucose area under the curve (sampled from pre-dose to 4 hours post meal) was reduced from Baseline to Day 7 by 169.3 mg*hr/dL on LX4211 compared to placebo (p=0.003). Day 8 SBP reductions were 11.4 mmHg on LX4211 and 0.0 mmHg on placebo (p=0.045 for difference between groups). Patients with greater RI (eGFR <45 mL/min/1.73 m2) treated with LX4211 (N=6) had a 10.5 mmHg SBP reduction compared to 0.3 mmHg on placebo (N=9). The difference between seated and standing SBP did not change with LX4211 (0.0 mmHg change, Day 8 vs. Baseline). There were no reports of hypotension, hypovolemia, no serious adverse events, and no patient discontinued due to an adverse event. Mild hypoglycemia was reported in 1 LX4211 patient compared to 2 placebo patients. Conclusions: LX4211 may reduce SBP and enhance glycemic control in T2DM patients with moderate to severe RI.

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