Down-regulation of Na+ transporters and AQP2 is responsible for acyclovir-induced polyuria and hypophosphatemia Lúcia Andrade, Nancy A. Rebouças, Antonio.

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Down-regulation of Na+ transporters and AQP2 is responsible for acyclovir-induced polyuria and hypophosphatemia Lúcia Andrade, Nancy A. Rebouças, Antonio Carlos Seguro Kidney International Volume 65, Issue 1, Pages 175-183 (January 2004) DOI: 10.1111/j.1523-1755.2004.00359.x Copyright © 2004 International Society of Nephrology Terms and Conditions

Figure 1 Plasma phosphate concentration before and after initiation of acyclovir (ACY) treatment(N = 8). Concentration decreased significantly after initiation of treatment (pre-ACY vs. other days). Kidney International 2004 65, 175-183DOI: (10.1111/j.1523-1755.2004.00359.x) Copyright © 2004 International Society of Nephrology Terms and Conditions

Figure 2 Serum magnesium and calcium levels before and after initiation of acyclovir (ACY) treatment. Hypomagnesemia and hypercalcemia developed in ACY-treated animals. Kidney International 2004 65, 175-183DOI: (10.1111/j.1523-1755.2004.00359.x) Copyright © 2004 International Society of Nephrology Terms and Conditions

Figure 3 Urine osmolality before (pre-acyclovir [ACY]) and after initiation of treatment. ACY-treated rats had markedly lower urine osmolality: pre-ACY vs. 8th day. Kidney International 2004 65, 175-183DOI: (10.1111/j.1523-1755.2004.00359.x) Copyright © 2004 International Society of Nephrology Terms and Conditions

Figure 4 Urinary osmolality before and after 24hours and 48hours of water deprivation for control and acyclovir (ACY)-treated rats. Kidney International 2004 65, 175-183DOI: (10.1111/j.1523-1755.2004.00359.x) Copyright © 2004 International Society of Nephrology Terms and Conditions

Figure 5 Proximal Na-Pi cotransporter (Na-Pi-IIa) Northern hybridization. (A) Densitometric analyses revealing a marked decrease in cortex Na-Pi-IIa mRNA levels in treated animals. (B) Representative Northern blot showing apical Na-Pi-IIa and 18S transcript levels in cortex from control and treated-rats. Kidney International 2004 65, 175-183DOI: (10.1111/j.1523-1755.2004.00359.x) Copyright © 2004 International Society of Nephrology Terms and Conditions

Figure 6 Semiquantitative immunoblotting of membrane fractions of kidney cortex. (A) Densitometric analysis revealed a decrease in cortex Na-Pi abundance in acyclovir (ACY)-treated rats. (B) Immunoblots reacted with anti-Na-Pi (anti-Na-Pi-IIa) revealed a band of approximately 85 kD. Densitometric analysis of Na-Pi-IIa protein was normalized by densitometric analysis of actin protein. Kidney International 2004 65, 175-183DOI: (10.1111/j.1523-1755.2004.00359.x) Copyright © 2004 International Society of Nephrology Terms and Conditions

Figure 7 Apical Na-k-2Cl (NKCC2) cotransporter Northern hybridization. (A) Densitometric analyses revealing a marked decrease in medulla NKCC2 mRNA levels in treated animals. (B) Representative Northern blot showing apical NKCC2 and β-actin transcript levels in medullas from control and treated rats. Kidney International 2004 65, 175-183DOI: (10.1111/j.1523-1755.2004.00359.x) Copyright © 2004 International Society of Nephrology Terms and Conditions

Figure 8 Semiquantitative immunoblotting of membrane fractions of kidney medulla. (A) Densitometric analysis revealed a decrease in medulla NKCC2 (Na-K-2Cl) abundance in ACY-treated rats. (B) Immunoblots reacted with anti-NKCC2 revealed a band of approximately 146 to 176 kD (centered at 161 kD). Densitometric analysis of NKCC2 protein was normalized by densitometric analysis of actin protein. Kidney International 2004 65, 175-183DOI: (10.1111/j.1523-1755.2004.00359.x) Copyright © 2004 International Society of Nephrology Terms and Conditions

Figure 9 Semiquantitative immunoblotting of membrane fractions of kidney medulla. (A) Densitometric analysis revealed a decrease in medulla aquaporin 2 (AQP2) abundance in acyclovir (ACY)-treated rats. (B) Immunoblots reacted with anti-AQP2 revealed 29- and 35 to 50-kD AQP2 bands, representing nonglycosylated and glycosylated forms of AQP2, respectively. Densitometric analysis of AQP2 protein was normalized by densitometric analysis of villin protein. Kidney International 2004 65, 175-183DOI: (10.1111/j.1523-1755.2004.00359.x) Copyright © 2004 International Society of Nephrology Terms and Conditions