Effect of Spironolactone and Amiloride on Thiazolidinedione-Induced Fluid Retention in South Indian Patients with Type 2 Diabetes

Vijay Viswanathan; Viswanathan Mohan; Poongothai Subramani; Nandakumar Parthasarathy; Gayathri Subramaniyam; Deepa Manoharan; Chandru Sundaramoorthy; Luigi Gnudi; Janaka Karalliedde; Giancarlo Viberti

doi:10.2215/CJN.06330612

Effect of Spironolactone and Amiloride on Thiazolidinedione-Induced Fluid Retention in South Indian Patients with Type 2 Diabetes

Vijay Viswanathan, Viswanathan Mohan, Poongothai Subramani, Nandakumar Parthasarathy, Gayathri Subramaniyam, Deepa Manoharan, Chandru Sundaramoorthy, Luigi Gnudi, Janaka Karalliedde^*, Giancarlo Viberti

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

14 Citations (Scopus)

Abstract

Background and objectives Thiazolidinediones (pioglitazone and rosiglitazone) induce renal epithelial sodium channel (ENaC) mediated sodium reabsorption, resulting in plasma volume (PV) expansion. Incidence and long-term management of fluid retention induced by thiazolidinediones remain unclear.

Design, setting, participants, & measurements In a 4-week run-in period, rosiglitazone, 4 mg twice daily, was added to a background anti-diabetic therapy in 260 South Indian patients with type 2 diabetes mellitus. Patients with PV expansion (absolute reduction in hematocrit in run-in, >= 1.5 percentage points) entered a randomized, placebo-controlled study to evaluate effects of amiloride and spironolactone on attenuating rosiglitazone-induced fluid retention. Primary endpoint was change in hematocrit in each diuretic group versus placebo (control group).

Results Of the 260 patients, 70% (n=180) had PV expansion. These 180 patients (70% male; mean age, 47.8 years [range, 30-80 years]) were randomly assigned to rosiglitazone, 4 mg twice daily, plus spironolactone, 50 mg once daily; rosiglitazone, 4 mg twice daily, plus amiloride, 10 mg once daily; or rosiglitazone, 4 mg twice daily, plus placebo for 24 weeks. Hematocrit continued to decrease significantly in control and spironolactone groups (mean absolute change, -1.2 [P=0.01] and -0.7 [P=0.02] percentage points, respectively), suggesting continued PV expansion. No change occurred with amiloride (mean change, 0.0 percentage points). Amiloride, but not spironolactone, was superior to control (mean hematocrit difference [95% confidence interval] relative to control, 1.27 [0.21-2.55] and 0.49 [-0.79-1.77] percentage points [P=0.04 and P=0.61], respectively).

Conclusions Prevalence of rosiglitazone-induced fluid retention in South Indian patients with type 2 diabetes is high. Amiloride, a direct ENaC blocker, but not spironolactone, prevented protracted fluid retention in these patients.

Original language	English
Article number	N/A
Pages (from-to)	225-232
Number of pages	8
Journal	Journal of the American Society of Nephrology
Volume	8
Issue number	2
DOIs	https://doi.org/10.2215/CJN.06330612
Publication status	Published - 7 Feb 2013

Keywords

CONGESTIVE-HEART-FAILURE
ROSIGLITAZONE
METAANALYSIS
THERAPY
VOLUME
DEATH
RISK

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.2215/CJN.06330612

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Viswanathan, V., Mohan, V., Subramani, P., Parthasarathy, N., Subramaniyam, G., Manoharan, D., Sundaramoorthy, C., Gnudi, L., Karalliedde, J., & Viberti, G. (2013). Effect of Spironolactone and Amiloride on Thiazolidinedione-Induced Fluid Retention in South Indian Patients with Type 2 Diabetes. Journal of the American Society of Nephrology, 8(2), 225-232. Article N/A. https://doi.org/10.2215/CJN.06330612

@article{d3058f6f772f4e1e8623e70362db86e4,

title = "Effect of Spironolactone and Amiloride on Thiazolidinedione-Induced Fluid Retention in South Indian Patients with Type 2 Diabetes",

abstract = "Background and objectives Thiazolidinediones (pioglitazone and rosiglitazone) induce renal epithelial sodium channel (ENaC) mediated sodium reabsorption, resulting in plasma volume (PV) expansion. Incidence and long-term management of fluid retention induced by thiazolidinediones remain unclear. Design, setting, participants, & measurements In a 4-week run-in period, rosiglitazone, 4 mg twice daily, was added to a background anti-diabetic therapy in 260 South Indian patients with type 2 diabetes mellitus. Patients with PV expansion (absolute reduction in hematocrit in run-in, >= 1.5 percentage points) entered a randomized, placebo-controlled study to evaluate effects of amiloride and spironolactone on attenuating rosiglitazone-induced fluid retention. Primary endpoint was change in hematocrit in each diuretic group versus placebo (control group). Results Of the 260 patients, 70% (n=180) had PV expansion. These 180 patients (70% male; mean age, 47.8 years [range, 30-80 years]) were randomly assigned to rosiglitazone, 4 mg twice daily, plus spironolactone, 50 mg once daily; rosiglitazone, 4 mg twice daily, plus amiloride, 10 mg once daily; or rosiglitazone, 4 mg twice daily, plus placebo for 24 weeks. Hematocrit continued to decrease significantly in control and spironolactone groups (mean absolute change, -1.2 [P=0.01] and -0.7 [P=0.02] percentage points, respectively), suggesting continued PV expansion. No change occurred with amiloride (mean change, 0.0 percentage points). Amiloride, but not spironolactone, was superior to control (mean hematocrit difference [95% confidence interval] relative to control, 1.27 [0.21-2.55] and 0.49 [-0.79-1.77] percentage points [P=0.04 and P=0.61], respectively). Conclusions Prevalence of rosiglitazone-induced fluid retention in South Indian patients with type 2 diabetes is high. Amiloride, a direct ENaC blocker, but not spironolactone, prevented protracted fluid retention in these patients. ",

keywords = "CONGESTIVE-HEART-FAILURE, ROSIGLITAZONE, METAANALYSIS, THERAPY, VOLUME, DEATH, RISK",

author = "Vijay Viswanathan and Viswanathan Mohan and Poongothai Subramani and Nandakumar Parthasarathy and Gayathri Subramaniyam and Deepa Manoharan and Chandru Sundaramoorthy and Luigi Gnudi and Janaka Karalliedde and Giancarlo Viberti",

year = "2013",

month = feb,

day = "7",

doi = "10.2215/CJN.06330612",

language = "English",

volume = "8",

pages = "225--232",

journal = "Journal of the American Society of Nephrology",

issn = "1555-9041",

publisher = "American Society of Nephrology",

number = "2",

}

Viswanathan, V, Mohan, V, Subramani, P, Parthasarathy, N, Subramaniyam, G, Manoharan, D, Sundaramoorthy, C, Gnudi, L , Karalliedde, J & Viberti, G 2013, 'Effect of Spironolactone and Amiloride on Thiazolidinedione-Induced Fluid Retention in South Indian Patients with Type 2 Diabetes', Journal of the American Society of Nephrology, vol. 8, no. 2, N/A, pp. 225-232. https://doi.org/10.2215/CJN.06330612

TY - JOUR

T1 - Effect of Spironolactone and Amiloride on Thiazolidinedione-Induced Fluid Retention in South Indian Patients with Type 2 Diabetes

AU - Viswanathan, Vijay

AU - Mohan, Viswanathan

AU - Subramani, Poongothai

AU - Parthasarathy, Nandakumar

AU - Subramaniyam, Gayathri

AU - Manoharan, Deepa

AU - Sundaramoorthy, Chandru

AU - Gnudi, Luigi

AU - Karalliedde, Janaka

AU - Viberti, Giancarlo

PY - 2013/2/7

Y1 - 2013/2/7

N2 - Background and objectives Thiazolidinediones (pioglitazone and rosiglitazone) induce renal epithelial sodium channel (ENaC) mediated sodium reabsorption, resulting in plasma volume (PV) expansion. Incidence and long-term management of fluid retention induced by thiazolidinediones remain unclear. Design, setting, participants, & measurements In a 4-week run-in period, rosiglitazone, 4 mg twice daily, was added to a background anti-diabetic therapy in 260 South Indian patients with type 2 diabetes mellitus. Patients with PV expansion (absolute reduction in hematocrit in run-in, >= 1.5 percentage points) entered a randomized, placebo-controlled study to evaluate effects of amiloride and spironolactone on attenuating rosiglitazone-induced fluid retention. Primary endpoint was change in hematocrit in each diuretic group versus placebo (control group). Results Of the 260 patients, 70% (n=180) had PV expansion. These 180 patients (70% male; mean age, 47.8 years [range, 30-80 years]) were randomly assigned to rosiglitazone, 4 mg twice daily, plus spironolactone, 50 mg once daily; rosiglitazone, 4 mg twice daily, plus amiloride, 10 mg once daily; or rosiglitazone, 4 mg twice daily, plus placebo for 24 weeks. Hematocrit continued to decrease significantly in control and spironolactone groups (mean absolute change, -1.2 [P=0.01] and -0.7 [P=0.02] percentage points, respectively), suggesting continued PV expansion. No change occurred with amiloride (mean change, 0.0 percentage points). Amiloride, but not spironolactone, was superior to control (mean hematocrit difference [95% confidence interval] relative to control, 1.27 [0.21-2.55] and 0.49 [-0.79-1.77] percentage points [P=0.04 and P=0.61], respectively). Conclusions Prevalence of rosiglitazone-induced fluid retention in South Indian patients with type 2 diabetes is high. Amiloride, a direct ENaC blocker, but not spironolactone, prevented protracted fluid retention in these patients.

AB - Background and objectives Thiazolidinediones (pioglitazone and rosiglitazone) induce renal epithelial sodium channel (ENaC) mediated sodium reabsorption, resulting in plasma volume (PV) expansion. Incidence and long-term management of fluid retention induced by thiazolidinediones remain unclear. Design, setting, participants, & measurements In a 4-week run-in period, rosiglitazone, 4 mg twice daily, was added to a background anti-diabetic therapy in 260 South Indian patients with type 2 diabetes mellitus. Patients with PV expansion (absolute reduction in hematocrit in run-in, >= 1.5 percentage points) entered a randomized, placebo-controlled study to evaluate effects of amiloride and spironolactone on attenuating rosiglitazone-induced fluid retention. Primary endpoint was change in hematocrit in each diuretic group versus placebo (control group). Results Of the 260 patients, 70% (n=180) had PV expansion. These 180 patients (70% male; mean age, 47.8 years [range, 30-80 years]) were randomly assigned to rosiglitazone, 4 mg twice daily, plus spironolactone, 50 mg once daily; rosiglitazone, 4 mg twice daily, plus amiloride, 10 mg once daily; or rosiglitazone, 4 mg twice daily, plus placebo for 24 weeks. Hematocrit continued to decrease significantly in control and spironolactone groups (mean absolute change, -1.2 [P=0.01] and -0.7 [P=0.02] percentage points, respectively), suggesting continued PV expansion. No change occurred with amiloride (mean change, 0.0 percentage points). Amiloride, but not spironolactone, was superior to control (mean hematocrit difference [95% confidence interval] relative to control, 1.27 [0.21-2.55] and 0.49 [-0.79-1.77] percentage points [P=0.04 and P=0.61], respectively). Conclusions Prevalence of rosiglitazone-induced fluid retention in South Indian patients with type 2 diabetes is high. Amiloride, a direct ENaC blocker, but not spironolactone, prevented protracted fluid retention in these patients.

KW - CONGESTIVE-HEART-FAILURE

KW - ROSIGLITAZONE

KW - METAANALYSIS

KW - THERAPY

KW - VOLUME

KW - DEATH

KW - RISK

U2 - 10.2215/CJN.06330612

DO - 10.2215/CJN.06330612

M3 - Article

SN - 1555-9041

VL - 8

SP - 225

EP - 232

JO - Journal of the American Society of Nephrology

JF - Journal of the American Society of Nephrology

IS - 2

M1 - N/A

ER -

Effect of Spironolactone and Amiloride on Thiazolidinedione-Induced Fluid Retention in South Indian Patients with Type 2 Diabetes

Abstract

Keywords

UN SDGs

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