Preservation of Residual Renal Function with Limited Water Removal in Hemodialysis Patients

Abstract

Residual renal function (RRF) is of paramount importance for hemodialysis (HD) adequacy, morbidity, and mortality. Some studies have shown that overhydration is beneficial for preservation of RRF, but it can also increase the probability of adverse events such as hypertension and heart failure in HD patients. To determine the optimal amount of dehydration, we performed HD with limited water removal in HD patients. Eighteen HD patients included in this self-controlled study underwent HD with limited water removal. Water removal volume was determined by a previous volume as follows. Total water removal volume was divided into levels: ≤3.0, 3.0–9.0, and >9.0 L per week. Water removal was performed to obtain dry weight in the last dialysis, and was performed three times with a ratio of 1:1:2 and 2:2:3, respectively. Urine volume, endogenous creatinine clearance rate, Kt/V, hemoglobin, and serum albumin were recorded before and after the study at 3, 6, 9, and 12 months. The follow-up period was 12 months. Ten patients withdrew from the study because of adverse events including hypertension (n = 3), heart failure (n = 3), angina (n = 1), polycystic kidney rupture (n = 1), obvious edema (n = 1), and one patient had too much interdialytic weight gain to continue. As a result, we stopped this study after 1 month. Our data suggest that the preservation of RRF with limited water removal in HD patients must be interpreted with caution.

• residual renal function
• limited water removal
• hemodialysis
• preservation
• adverse events

The presence of residual renal function (RRF) is important for influencing morbidity, mortality, and the quality of life of hemodialysis (HD) patients.^1–3 Previous studies have shown that there are many measures that can be taken for preservation of RRF in HD patients, such as offering peritoneal dialysis as an initial dialysis modality, use of ultrapure dialysate and biocompatible membranes during HD, avoiding aminoglycosides, and nonsteroidal anti-inflammatory drugs unless medically indicated.⁴ In addition, some studies have reported that preservation of RRF is linked to a chronic state of overhydration in dialysis patients.⁵ Gunal et al.⁶ suggested that the persistence of RRF in patients with end-stage renal disease (ESRD) might largely depend on overhydration. However, slight overhydration may result in hypertension, and its consequences, left ventricular hypertrophy and cardiac disease.^7,8 Data are scarce on the optimal water removal volume for preservation of RRF in HD patients. This study aimed to investigate the relationship between preservation of RRF and limited water removal to maintain slight overhydration in HD patients.

SUBJECTS AND METHODS

Study Population

Patients were selected from the population undergoing HD in the dialysis center of our hospital. The criteria for entering the study were as follows: (1) urine volume >200 mL/24 h⁹; (2) blood pressure <150/90 mmHg, without or with ≤ two antihypertensive drugs; and (3) patients had begun HD previously and maintained the same dialysis schedule for at least 3 months. Exclusion criteria were as follows: (1) major comorbid conditions (congestive heart failure, edema, or an auxiliary examination indicated that they had obvious fluid retention); (2) chronic infection; (3) malignancy; and (4) previously treated with peritoneal dialysis.

Eighteen patients (10 males and 8 females, aged from 28 to 80) were enrolled in this study. Hypertension was defined by a repeated predialysis blood pressure of more than 140/90 mmHg and it was documented in the majority of the patients (13/18). Prescribed medication included antihypertensive drugs, and medication for coronary heart disease, diabetes, and renal anemia.

Study Design

This was a self-controlled study. We compared the mean urine volume and endogenous creatinine clearance rate (eCCR) before and after the study at 3, 6, 9, and 12 months. The study was approved by the Ethics Committee of the Beijing Friendship Hospital, Capital Medical University. Eligible patients who had given their informed consent would accept HD with limited water removal for 12 months. Water removal volume was determined by a previous volume as follows: (1) total water removal volume was no more than 3.0 L per week and water removal was only performed to obtain dry weight in the last dialysis in a week (Friday or Saturday); (2) total water removal volume was 3.0–9.0 L in a week and water removal was performed in all three dialysis sessions, and the ratio was 1:1:2; and (3) total water removal volume was more than 9.0 L and water removal was performed in all three dialysis sessions, and the ratio was 2:2:3.

Patients with water retention can absorb water by controlling sodium, water through diet control, and diuretic application if diet control cannot work. If patients had hypertension in the study, calcium-channel blockers were considered first, and angiotensin-converting enzyme inhibitors and angiotensin-receptor blockers were avoided if possible.

The endpoints included loss of death, RRF (<200 mL/24 h), hypertension (>150/90 mmHg or using more than three antihypertensive drugs), a transplant, or a transfer to other modalities.

Study Parameters

The eCCR was recorded to measure RRF, and the 24-h urine volume, Kt/V, hemoglobin, and albumin were compared before and after the study at 3, 6, 9, and 12 months. In addition, patient-related data including age, sex, cause of ESRD, average blood flow rate, use of antihypertensive drugs, blood pressure, and adverse events (such as heart failure and edema) were also included.

Statistical Analysis

Data are given as mean ± SD. The variables including 24-h urine volume, eCCR, hemoglobin, and albumin before and after the study were compared by the F-test.

RESULTS

Study Population

The baseline characteristics in 18 patients at recruitment are shown in Tables 1 and 2.

Table 1. Baseline demographics, comorbidities, chronic renal disease, blood pressure, and use of antihypertensive drugs in the patients at recruitment.

Variable	Study population
Demographics
Number of patients (n)	18
Gender (males/females) (n)	10/8
Age (years)	54.17 ± 14.02 (28–80)
Cause of renal disease
Glomerulonephritis	6
Hypertension	4
Diabetes mellitus	2
Interstitial nephritis	1
Polycystic kidney disease	1
Obstructive nephropathy	1
Unknown	3
Comorbidities
Hypertension	13
Diabetes mellitus	4
CHD	2
Urethritis	1
Blood pressure (mmHg)
Systolic	130.78 ± 11.94 (102–147)
Diastolic	75.94 ± 11.43 (54–94)
Medication use
Beta-blocker	3
CCB	12
ARB	4

Note: CHD, coronary heart disease; CCB, calcium-channel blocker; ARB, angiotensin-receptor blocker.

Table 2. Indices of blood chemistry, residual renal function (RRF), and dialysis adequacy in patients at recruitment.

Variable	Study population
Dry weight	66.18 ± 10.81(49.50–89.20)
Kt/V urea per treatment	1.228 ± 0.292(0.751–2.04)
Blood flow rate	288.89 ± 23.24(220–330)
CCR (mL/min)	3.65 ± 2.74(0.48–9.82)
Urine output (m/24 h)	1122.22 ± 497.03(350–2150)
Hemoglobin (g/L)	114.61 ± 10.81(91.00–128.00)
Albumin (g/L)	39.21 ± 9.82(35.10–42.70)

Note: CCR, creatinine clearance rate.

Outcomes

From the 3rd to the 30th day after the study, 10 patients withdrew because of adverse events including three with hypertension, three with heart failure, one with angina, one with polycystic kidney rupture, one with obvious edema, and one with too much interdialytic weight gain to continue. More than half of the patients withdrew, and therefore, we stopped this study at 1 month after its initiation.

DISCUSSION

Avoidance of aggressive water removal, even without water removal, is beneficial for the preservation of RRF in dialysis patients.^10,11 Hyodo and Koutoku¹² compared the RRF in HD patients without water removal with that in patients with water removal, and the results showed that the urine volume in those without water removal was significantly larger.

However, the present study indicated that preservation of RRF with limited water removal in HD patients must be interpreted with caution. In our study, more than half of the patients had adverse events, including hypertension and heart failure. All events were closely related to fluid retention. Some studies have reported that overhydration is linked to hypertension and left ventricular hypertrophy.¹³ It is apparent that attempting to reduce blood pressure with drugs in dialysis patients, even if it is successful, does not obtain the desired goal of reducing cardiac damage, unless volume is corrected. In Hyodo and Koutoku’s study,¹² patients without water removal still had water removal performed when the body weight before the start of dialysis on each dialysis day exceeded 102.2% as a percentage of the dry weight, until the body weight reached dry weight. However, in our study, the regime of water removal resulted in patients having persistent overhydration until the third HD in a week. Therefore, overhydration was severe, which may have been the reason for adverse events in the patients.

If one of the most clinically significant benefits of RRF preservation is the ability to limit water retention with consequent hypertension and left ventricular hypertrophy, it would be counterproductive to keep patients overhydrated to maintain RRF. Moreover, previous studies have suggested that strict volume control can decrease blood pressure and improve cardiac conditions,^14,15 but overhydration increases hospitalization and mortality rates.^16,17 Therefore, the preservation of RRF should not be considered as a primary goal but as a means for improving patient survival.

In our study, we were unable to indicate an eligible regime of water removal, not only to preserve RRF, but also to decrease adverse events such as hypertension and heart failure. In addition, there are some limitations to our study. First, RRF in HD patients with different causes of renal disease decreases at different rates. In the present study, we did not investigate the association between the regime of water removal and RRF of HD patients with different causes of renal disease. Moreover, this was a self-controlled study with a small number of participants and limited follow-up. Therefore, large randomized controlled trials are required in the future.

In summary, a delicate balance exists between water removal and preservation of RRF in HD patients. Maintaining this balance is complicated, and further study is required to determine this issue.

ACKNOWLEDGMENTS

This work was supported by a grant from Beijing Municipal Science and Technology Commission Funds (D09050704310903).

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.