Therapeutic roles of thiazides and loop diuretics in blood pressure control and renal protection against chronic kidney disease.

Fluid overload secondary to loss of functional nephron mass can elevate blood pressure, which is characteristic of hypertension shown in chronic kidney disease (CKD). Therefore, it is logical to use diuretics at appropriate dose to lower blood pressure in patients with CKD and hypertension. Despite the theoretical background on the use of diuretics in CKD, there have been no definitive data on the effectiveness or safety of diuretics as first-line therapy for the management of hypertension in patients with CKD. Results from some clinical trials have demonstrated that diuretics would not lower blood pressure. They could even worsen electrolyte imbalance and kidney function when they are administered in patients with CKD. Major clinical practice guidelines on management of blood pressure or CKD have stated that evidence for benefits of thiazide diuretics is not conclusive yet in patients with advanced CKD, although loop diuretics are often effective for volume control at lower glomerular filtration rate. Recently, evidence for diuretics as effective blood pressure lowering agents in patients with advanced CKD is increasing. Renoprotective effect of thiazide or loop diuretics might represent a consequence of their influence on blood pressure or their ability to potentiate the effect of renin-angiotensin system blockade by making intraglomerular pressure more renin-angiotensin system-dependent, although their direct benefit on renal function remains controversial. This review summarizes recent data on the possible role of diuretics in lowering blood pressure, slowing the progression of kidney disease, and reducing cardiovascular risk in CKD patients.

Association Between Proton Pump Inhibitor Exposure and Acute Kidney Injury After Cardiac Surgery.

OBJECTIVE: To evaluate the association of preoperative proton pump inhibitor (PPI) exposure with incident acute kidney injury (AKI) after cardiac surgery. PATIENTS AND METHODS: The Severance cardiac surgery cohort included 9860 cardiac surgery patients aged 18 years or older. The National Health Insurance Service-senior cohort included 2933 patients aged 60 years or older who underwent cardiac surgery. Preoperative PPI exposure was defined as a PPI prescription within 3 weeks prior to cardiac surgery. Primary outcomes were postoperative AKI and AKI requiring dialysis (AKI-dialysis). RESULTS: In the Severance cardiac surgery cohort after propensity score matching for PPI exposure, incident AKI (44.0% [472 of 1073] vs 40.5% [1304 of 3219]) and AKI-dialysis (5.8% [62 of 1073] vs 3.7% [119 of 3219]) were more common in patients exposed to PPI than in those who were not. Hospital and intensive care unit stay durations were longer among PPI-exposed than PPI-nonexposed patients. Multivariable conditional logistic analyses revealed that PPI exposure was significantly associated with incident AKI (adjusted odds ratio [AOR], 1.21; 95% CI, 1.03 to 1.42; P=.02) and AKI-dialysis (AOR, 1.74; 95% CI, 1.15 to 2.63; P=.009). The National Health Insurance Service-Senior cohort had similar results, revealing a significant association between PPI exposure and incident AKI-dialysis (AOR, 1.87; 95% CI, 1.25 to 2.81; P=.003). Discontinuation of PPI prior to operation was associated with a lower odds of AKI development in both cohorts. CONCLUSION: Preoperative PPI exposure may be a modifiable risk factor for AKI among patients undergoing cardiac surgery.

Mixed- versus predilution hemodiafiltration effects on convection volume and small and middle molecule clearance in hemodialysis patients: a prospective randomized controlled trial.

BACKGROUND: The use of newly developed mixed-dilution hemodiafiltration (HDF) can supplement the weaknesses of pre- and postdilution HDF. However, it is unclear whether mixed-HDF performs well compared to predilution HDF. METHODS: We conducted a prospective, open-labeled, randomized controlled trial from two hemodialysis centers in Korea. Between January 2017 and September 2019, 60 patients who underwent chronic hemodialysis were randomly assigned at a 1:1 ratio to receive either predilution HDF (n = 30) or mixed-HDF (n = 30) for 6 months. We compared convection volume, changes in small- and medium-sized molecule clearance, high-sensitive C-reactive protein (hs-CRP) level, and dialysis-related parameters between the two dialysis modalities. RESULTS: A mean effective convection volume of 41.0 ± 10.3 L/session in the predilution HDF group and 51.5 ± 9.0 L/session in the mixed-HDF group was obtained by averaging values of three time-points. The difference in effective convection volume between the groups was 10.5 ± 1.3 L/session. This met the preset noninferiority criteria, suggesting that mixed-HDF was noninferior to predilution HDF. Moreover, the ß2-microglobulin reduction rate was greater in the mixed-HDF group than in the predilution HDF group, while mixed-HDF provided greater transmembrane pressure. There were no significant between-group differences in Kt/V urea levels, changes in predialysis hs-CRP levels, proportions of overhydration, or blood pressure values. Symptomatic intradialytic hypotension episodes and other adverse events occurred similarly in the two groups. CONCLUSION: Use of mixed-HDF was comparable to predilution HDF in terms of delivered convection volume and clinical parameters. Moreover, mixed-HDF provided better ß2-microglobulin clearance than predilution HDF.

Association of smoking with incident CKD risk in the general population: A community-based cohort study.

BACKGROUND: Chronic kidney disease (CKD) is a public health problem, and an unfavorable lifestyle has been suggested as a modifiable risk factor for CKD. Cigarette smoking is closely associated with cardiovascular disease and cancers; however, there is a lack of evidence to prove that smoking is harmful for kidney health. Therefore, we aimed to determine the relationship between cigarette smoking and CKD among healthy middle-aged adults. METHODS: Using the database from the Korean Genome and Epidemiology Study, we analyzed 8,661 participants after excluding those with baseline estimated glomerular filtration rate (eGFR)<60 ml/min/1.72 m2 or proteinuria. Exposure of interest was smoking status: never-, former-, and current-smokers. Primary outcome was incident CKD defined as eGFR <60 ml/min/1.73 m2 or newly developed proteinuria. RESULTS: The mean age of the subjects was 52 years, and 47.6% of them were males. There were 551 (6.4%) and 1,255 (14.5%) subjects with diabetes and hypertension, respectively. The mean eGFR was 93.0 ml/min/1.73 m2. Among the participants, 5,140 (59.3%), 1,336 (15.4%), and 2,185 (25.2%) were never-smokers, former-smokers, and current-smokers, respectively. During a median follow-up of 11.6 years, incident CKD developed in 1,941 (22.4%) subjects with a crude incidence rate of 25.1 (24.0-26.2) per 1,000 person-years. The multivariable Cox regression analysis after adjustment of confounding factors showed hazard ratios (95% confidence interval) of 1.13 (0.95-1.35) and 1.26 (1.07-1.48) for CKD development in the former- and current-smokers, compared with never-smokers. CONCLUSION: This study showed that smoking was associated with a higher risk of incident CKD among healthy middle-aged adults.