Should Diuretics Be Used To Protect Residual Renal Function During The First Year Of Hemodialysis?

The data for this study came from the DOPPS study, a prospective cohort study of adult CKD hemodialysis patients in 21 countries. Specifically, the researchers selected data from DOPPS phases 2 to 5, that is, data from 2002 to 2015. The inclusion criteria were hemodialysis patients due to CKD. In addition, if the history of dialysis was less than 1 year, the number of patients enrolled in a single center must be greater than 5. The researchers also selected patients who did not use diuretics during the same period as the control group. For patients who used diuretics, they were also divided into loop diuretics and other types of diuretics.

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The main endpoints of the study

① Diuretic use, that is, the use of diuretics in dialysis patients worldwide and whether there are international differences;

② Clinical endpoints, including all-cause death, all-cause hospitalization, hospitalization due to major adverse cardiovascular events (MACE) or heart failure, hospitalization due to heart failure, and hospitalization due to fractures;

③ CKD mineral and bone abnormalities (MBD)-related biomarkers, including blood calcium, blood phosphorus, parathyroid hormone (PTH), and total alkaline phosphatase.

④ Extracellular volume parameters, including systolic blood pressure (SBP) and diastolic blood pressure (DBP), interdialytic weight gain and residual urine volume.

Research results

1 Diuretic use

A total of 27,759 hemodialysis patients were included in this study. The study found that the longer the dialysis history, the lower the probability of receiving diuretic treatment at baseline, and this situation exists in all countries around the world. However, there are huge differences in whether diuretics are received at baseline in different countries. Among patients with a history of hemodialysis of less than 1 year, 84% of German dialysis patients received diuretic treatment, and only 24% in Spain. In addition, if the patient has residual urine, the diuretic use rate is 54%, and if there is no residual urine, the diuretic use rate is 38%.

The researchers also investigated whether hemodialysis patients with a dialysis age of more than 5 years are using diuretics. The study found that the diuretic use rate is less than 10% in the United States, New Zealand, Australia, Spain and Italy; it is about 30% in Germany and Sweden. The use rate was 38% for patients with residual urine and 9% for those without.

Of note, loop diuretics were the most commonly used diuretics in all countries, with other diuretics being prescribed in only 0-12% of cases. Most patients received furosemide, and only a small number of patients (6.8%) received two diuretics.

There was a large difference in the dose of loop diuretics prescribed in the first year of dialysis. The median daily dose was higher in Germany, Sweden, and France, while it was lowest in Spain and the United States. The researchers found that the ranking of doses was similar to the use of diuretics, with one exception: Japan. In Japan, although many hemodialysis patients received diuretics, the dose was the lowest.

Finally, the researchers found that older hemodialysis patients with cardiovascular disease and diabetes were more likely to receive diuretics.

2 Clinical endpoints

The researchers found that whether or not diuretics were used in the first year of dialysis did not significantly affect patients' clinical endpoints, including all-cause death, all-cause hospitalization, and hospitalization for MACE or heart failure. In terms of dose, compared with the control group, low-dose diuretics (<60 mg/d) were associated with a higher risk of hospitalization for MACE or heart failure (HR = 1.20; 95% CI, 1.05-1.37); medium-dose (60-200 mg/d) and high-dose (>200 mg/d) were associated with a higher rate of all-cause hospitalization, with HRs of 1.08 (95% CI, 1.01-1.16) and 1.11 (95% CI, 1.03-1.18), respectively. However, after correcting for multiple confounding factors such as cardiovascular history, there was no significant difference in mortality between the diuretic group and the control group.

3 CKD-MBD

Loop diuretics were associated with lower PTH (-11.6 pg/ml; 95% CI, -20.6 to -2.5) and total alkaline phosphatase (-2.3 IU/L; 95% CI, -4.8 to -0.3), but there was no dose dependence. In addition, patients with lower diuretic use had higher serum calcium, however, diuretic dose did not affect the increased risk of hospitalization due to fracture.

4 Extracellular volume parameters

The diuretic prescription was associated with slightly higher predialysis SBP and DBP. Lower interdialytic weight gain was associated with lower doses of loop diuretics (<60 mg/d, mean difference -0.30 kg; 95% Cl: -0.47 to -0.13). In addition, the use of diuretics was associated with residual urine volume >200 ml/d (OR = 1.51; 95% CI, 1.41-1.61), showing a dose-dependent (average daily dose >200 mg/d; OR = 1.73; 95% CI, 1.31-2.27).

Research discussion

This study showed that there were large differences in the use of diuretics for hemodialysis patients in different countries and regions. Although diuretics were associated with residual urine volume, overall, high-dose diuretics were not associated with improved clinical endpoints (including all-cause mortality) in patients. At the same time, medium-dose (60-200 mg/d) and high-dose (>200 mg/d) diuretics were associated with a higher rate of all-cause hospitalization, and low-dose (<60 mg/d) diuretics were associated with a higher risk of hospitalization for MACE or heart failure. However, the use of diuretics was not associated with an increased risk of fractures or elevated PTH levels.

In this study, data from 2002 to 2015 showed that no significant differences in diuretic use were observed. This suggests that in the past, the use of diuretics was more based on the experience of different countries, regions and medical institutions rather than detailed clinical evidence.

Previous studies have suggested that the use of diuretics in hemodialysis patients can improve patients' clinical hard endpoints, but this study found the opposite result. This may be due to the fact that the patients in this study were older (>1.3 years old), had a higher prevalence of heart failure (6% higher), and had a higher prevalence of other cardiovascular diseases (7% higher). In addition, this study was a prospective study, while previous studies were small sample, interventional studies. This suggests that more research and research methods may be needed to determine whether diuretics should be used in hemodialysis patients, especially in the first year of dialysis.

Despite adverse signals in all-cause hospitalization outcomes, patients treated with loop diuretics, even in patients using the maximum dose, were more likely to retain residual urine, which was confirmed in multivariate analysis at the institutional level, suggesting that prescription diuretics may help retain residual urine. However, reverse causality cannot be ruled out, that is, doctors only use diuretics in patients with residual urine or large residual urine volume. Therefore, whether diuretics can help patients maintain residual urine requires more research.

Research summary

In summary, the results of this study are inconsistent with previous studies, suggesting that diuretics cannot improve the clinical endpoints of hemodialysis patients, especially those in the first year of hemodialysis. Perhaps more research is needed to explore the optimal use of diuretics.

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