title: Renoprotective effects of thiazides combined with loop diuretics in patients with type 2 diabetic kidney disease.
abstract: OBJECTIVE
  Type 2 diabetic kidney disease (DKD) is frequently accompanied by uncontrollable hypertension due to the sodium sensitivity inherent in DKD and to diuretic-resistant edema. In general, diuretics are effective in treating this condition, but thiazide diuretics are thought to be innocuous in advanced chronic kidney disease (CKD). We examined the renoprotective effects of combination therapy with thiazides and loop diuretics in type 2 DKD patients with CKD stage G4 or G5.
  
  
  METHODS
  This study included 11 patients with type 2 DKD and an estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m(2) who were suffering from severe edema even with loop diuretics. Each patient received additional hydrochlorothiazide (HCTZ) therapy, which was continued for more than 12 months. We examined clinical parameters including blood pressure (BP), proteinuria, and eGFR before and after the addition of HCTZ.
  
  
  RESULTS
  Patients received a 13.6 ± 3.8 mg/day dose of HCTZ in addition to loop diuretics (azosemide: 120 mg/day in 6 cases, 60 mg/day in 3 cases and furosemide: 80 mg/day in 1 case, 120 mg/day in 1 case). Side effects of HCTZ were not observed in all patients. After the addition of HCTZ therapy, systolic and diastolic blood pressures (S-BP, D-BP) as well as proteinuria significantly decreased (S-BP: at 6 months, p < 0.05 and 12 months, p < 0.01 vs. 0 month, D-BP: at 12 months, p < 0.05 vs. 0 month, proteinuria: at 6 months, p < 0.05 and 12 months, p < 0.01 vs. 0 month). The annual decline in eGFR was not significantly different before and after HCTZ therapy (-7.7 ± 8.5 and -8.4 ± 4.8 mL/min/1.73 m(2)/year, respectively).
  
  
  CONCLUSIONS
  Our findings suggest that the combination of HCTZ and loop diuretics improves BP levels, and decreases proteinuria even in advanced stage type 2 DKD patients with severe edema. The addition of HCTZ therapy was not found to negatively affect the change in eGFR in the present study.
authors.affiliation: Division of Nephrology, First Department of Integrated Medicine, Saitama Medical Center, Jichi Medical University, 1-847 Amanuma-cho, Omiya-ku, Saitama, Saitama, 330-8503, Japan.
authors.forename: Taro
authors.initials: T
authors.lastname: Hoshino
authors.forename: Susumu
authors.initials: S
authors.lastname: Ookawara
authors.forename: Haruhisa
authors.initials: H
authors.lastname: Miyazawa
authors.forename: Kiyonori
authors.initials: K
authors.lastname: Ito
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Ueda
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Kaku
authors.forename: Keiji
authors.initials: K
authors.lastname: Hirai
authors.forename: Honami
authors.initials: H
authors.lastname: Mori
authors.forename: Izumi
authors.initials: I
authors.lastname: Yoshida
authors.forename: Kaoru
authors.initials: K
authors.lastname: Tabei
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000959:Antihypertensive Agents / Q000627:therapeutic use; D001794:Blood Pressure; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D003928:Diabetic Nephropathies / Q000150:complications* / Q000503:physiopathology; D004232:Diuretics / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D004487:Edema / Q000209:etiology*; D005260:Female; D005665:Furosemide / Q000627:therapeutic use; D005919:Glomerular Filtration Rate; D006801:Humans; D006852:Hydrochlorothiazide / Q000627:therapeutic use*; D006973:Hypertension / Q000188:drug therapy* / Q000209:etiology; D008297:Male; D008875:Middle Aged; D011507:Proteinuria / Q000188:drug therapy / Q000209:etiology; D012076:Renal Agents / Q000627:therapeutic use*; D012189:Retrospective Studies; D049994:Sodium Potassium Chloride Symporter Inhibitors / Q000627:therapeutic use*; D013424:Sulfanilamides / Q000627:therapeutic use; D013777:Tetrazoles; D013876:Thiophenes; D000096926:Benzenesulfonamides
chemical_list: D000959:Antihypertensive Agents; D004232:Diuretics; D005665:Furosemide; D006852:Hydrochlorothiazide; D012076:Renal Agents; D049994:Sodium Potassium Chloride Symporter Inhibitors; D013424:Sulfanilamides; C018222:azosemide; D013777:Tetrazoles; D013876:Thiophenes; D000096926:Benzenesulfonamides