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Saudi Journal of Kidney Diseases and Transplantation
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ORIGINAL ARTICLE  
Year : 2013  |  Volume : 24  |  Issue : 6  |  Page : 1170-1174
Effects of oral enalapril and verapamil on dialysis adequacy and solute clearance in chronic ambulatory peritoneal dialysis


1 Nephrology Department, Modares Hospital, Shahid Beheshti University of Medical Science, Tehran, Iran
2 Emam Hossein Hospital, Shahid Beheshti University of Medical Science, Tehran, Iran

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Date of Web Publication13-Nov-2013
 

   Abstract 

Peritoneal dialysis offers several advantages such as better clearance of intermediate/large molecules and better preservation of renal residual function when compared with hemodialysis. However, dialysis adequacy is one of the subjects of concern of this modality. There are some drugs that are capable of influencing solute transport in the peritoneum, such as acetyle co-enzyme inhibitors (ACE-I) medications and calcium channel blockers. Captopril and Verapamil are often mentioned, but their use has shown varying conclusions and initial studies were performed with the intra-peritoneal administration of these drugs and there are only a few studies on the effect of the oral administration of these drugs. This study was undertaken with the aim to evaluate the effects of oral administration of Verapamil and Enalapril among continuous ambulatory peritoneal dialysis (CAPD) patients. The results of this study showed that Verapamil and Enalapril do not have any effects on glucose, creatinine, sodium, potassium and urea clearance (during the 4-h peritoneal equilibration test (PET) test). However, it was shown that Enalapril significantly increased the peritoneal urea Kt/V and caused a meaningful decrease in the diastolic and mean blood pressures. Therefore, we feel that Enalapril may be administered as an anti-hypertensive medication of choice in CAPD patients, which can also result in better dialysis adequacy. However, further studies with larger sample sizes are needed in the future.

How to cite this article:
Atabak S, Taziki O, Argani H, Abolghasemi R, Zangneh HF, Rahmani L. Effects of oral enalapril and verapamil on dialysis adequacy and solute clearance in chronic ambulatory peritoneal dialysis. Saudi J Kidney Dis Transpl 2013;24:1170-4

How to cite this URL:
Atabak S, Taziki O, Argani H, Abolghasemi R, Zangneh HF, Rahmani L. Effects of oral enalapril and verapamil on dialysis adequacy and solute clearance in chronic ambulatory peritoneal dialysis. Saudi J Kidney Dis Transpl [serial online] 2013 [cited 2019 Nov 13];24:1170-4. Available from: http://www.sjkdt.org/text.asp?2013/24/6/1170/121274

   Introduction Top


Peritoneal dialysis (PD), among the modalities of renal replacement therapy, possesses several advantages such as high biocompatibility of the peritoneum, better clearance of intermediate/ large molecules and better preservation of renal residual function. However, dialysis adequacy is one of the subjects of concern of this modality, evaluated by creatinine clearance and Kt/V. Solute transport in peritoneal dialysis depends on arterial blood pressure, visceral blood flow, oncotic pressure, peritoneal surface and its permeability. There are some drugs that are capable of influencing solute transport in the peritoneum. The activity of the renin-angiotensin-aldosterone system (RAAS) plays an important role in creating high blood pressure in these patients. Inhibiting this effect by means of ACE-I medications will result in decreased angiotensin II (AgII) effects such as vasoconstriction block, increase in the production of vasodilator prostaglandins, decreased kinin degradation and decreased sympathetic system activity.

Several clinical and experimental studies have shown that some of these drugs are able to alter water and solute transportation through the peritoneal membrane. [1],[2],[3],[4],[5] The majority of these medications were vasodilators or antihypertensive medications, among which Captopril [6] and Verapamil [7] are often mentioned, but their use has shown varying conclusions. Initial studies were performed with the intraperitoneal administration of these drugs, and there are only few studies on the effect of the oral administration of these drugs. One study showed that the oral administration of Enalapril had resulted in an increased peritoneal creatinine clearance. [1] Another study performed in 2005 concluded that the oral administration of Losartan, Verapamil or Prazocin substantially increased the creatinine clearance, urea Kt/V and ultrafiltration in 24 h. [8]

Therefore, taking into account the utmost importance of dialysis adequacy in peritoneal dialysis, [9] utilizing some oral medications in order to increase the dialysis dose would be helpful as the oral administration route is easier than the intraperitoneal route. Therefore, this study was undertaken with the aim of evaluating the effects of the oral administration of Verapamil and Enalapril on solute and water transport, urea Kt/V and creatinine clearance in continuous ambulatory peritoneal dialysis (CAPD) patients.


   Methods Top


This study was performed on a randomized controlled crossover clinical trial basis in a tertiary care educational hospital (Modares Hospital) and Shafa clinic in Tehran. All the cases under study were being dialyzed four times per day and each time with 2 L of 1.25% PD solution. The inclusion criteria were:

  1. The patient has started PD at least 1 month prior to entering the study
  2. The patient has not experienced peritonitis within the past 2 months
  3. The blood pressure is <120/90 mmHg.


The exclusion criteria were:

  1. Heart failure
  2. History of myocardial infarction (MI) and/ or cerebral infarction
  3. Uncontrolled and severe high blood pressure (systolic blood pressure >180 mmHg and diastolic blood pressure >120 mmHg)
  4. Heart block
  5. Renal artery stenosis
  6. Sensitivity to Verapamil or Enalapril.


Consent statements were obtained from all patients before their entry into the study. Twenty-two appropriate peritoneal dialysis patients were selected for the study. After obtaining consent from the patients, they were requested to discontinue their anti-hypertensive mediations for 1 week. Of course, all these patients were under close observation during this period by twice daily blood pressure measurements at home and were excluded quickly from the study by the physician once any adverse sign and symptom occurred. After 1 week of discontinuation of the anti-hypertensive drugs, the cases underwent blood pressure measurement, a 4-h PET test and measurement of creatinine clearance and urea Kt/V (urea and creatinine and 24-h urine collection). Patients' blood pressures were measured using a mercury column manometer by the duty nurse after 10 min of rest. The blood pressure for each patient was measured three times in 10-min intervals and the average was recorded as their blood pressure value. In order to measure creatinine clearance and urea Kt/V, a sample quantity amounting to 1% of the volume was collected from the fluid drained during each cycle within 24 h and was mixed together. Ten milliliters of the resultant solution, 24-h urine collection of the patient (those who still had urine production) and his serum sample for measuring urea and creatinine were collected and delivered to the Modares Hospital laboratory for analysis.

Following a measurement of the baseline values, the patients were randomly divided into two groups. One group was treated with Enalapril whereas the other group received Verapamil. Enalapril was administered at 5 mg twice daily and Verapamil was administered at 80 mg twice daily. Patients' blood pressures were measured again 2 days after starting the above-mentioned medications to evaluate the necessity of medication dose alterations (increasing or decreasing the dose). Patients were treated for 1 week with this regimen. Afterwards, their blood pressures, urea Kt/V and creatinine clearance were measured and the PET test was performed for each and every patient again followed by 3 days of a washout period for each patient. During this period, and also during the whole study period, patients continued their other medications such as folic acid, calcium carbonate, calcitriol and furosemide.

In order to prevent any overlapping effects of medications in the second stage of drug administration in the study, a 3-day washout period was assigned for all patients, which seems adequate taking into account the pharmacologic half-lives of the medications (2 h for Enalapril and 4.5-12 h for Verapamil). After 3 days of complete discontinuation of the drugs (Enalapril and Verapamil), Enalapril was administered for the group previously treated by Verapamil and, respectively, Verapamil was administered for the patients previously receiving Enalapril. This second period of medication administration lasted 1 week. The PET test was performed and urea Kt/V, creatinine clearance and blood pressures were measured for all patients again before and after this 1 week of drug administration.


   Data Analysis Top


Following data collection, each medication was compared with the baseline information using the Wilcoxon Rank test and the difference of each medication was compared with the baseline by the Freidman test. The data collected in the study were statistically analyzed by SPSS version 16 software. P <0.05 was assumed to be significant.


   Results Top


Twenty patients were studied. Two patients were excluded due to blood pressure changes. The primary characteristics of the included patients are mentioned in [Table 1]. All the peritoneal transport cases were present among the patients. The effects of Enalapril and Verapamil on the PET test, urea Kt/V and peritoneal creatinine clearance are mentioned in [Table 2].
Table 1: Basic characteristics of the patients.

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Table 2: Effect of Verapamil and Enalapril on dialysate/plasma (D/P) of potassium, sodium and total protein.

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Neither Enalapril, nor Verapamil had any effects on solute clearance in the 4-h PET test [Table 3]. The urea Kt/V (total) was basically 2.12, which turned to be 2.20 after Verapamil administration and 2.42 after Enalapril administration (P = 0.07). The urea Kt/V (kidney) did not have any significant changes in patients after the administration of Enalapril and Verapamil. The peritoneal urea Kt/V did not change significantly after Verapamil administration, whereas it increased substantially after Enalapril administration (P = 0.01). The changes in total creatinine clearance after Verapamil and Enalapril administration were not significant.
Table 3: Effect of Verapamil and Enalapril on urea and creatinine clearance.

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The changes in renal creatinine clearance following administration of the mentioned drugs were not significant. Similarly, the peritoneal creatinine clearance did not change significantly after administration of the medications. Patients' systolic blood pressure decreased 17 mmHg after receiving Verapamil (P = 0.06), while the decrease was 21 ± 5 mmHg following the administration of Enalapril (P = 0.14). Patients' diastolic blood pressure decreased by 10 ± 3 mmHg (P = 0.1) and 9 ± 3 mmHg (P = 0.02) following the administration of Verapamil and Enalapril, respectively. The effect of Enalapril on the diastolic blood pressure was significant.


   Discussion Top


The results of this study show that Verapamil and Enalapril do not have any effects on glucose, creatinine, sodium, potassium and urea clearance (during the 4-h PET test). There results are in keeping with the conclusions of several other studies. [1],[8],[10],[11],[12] Of course, in some studies, the medications were administered through the intraperitoneal route. [2],[3]

Other studies showed that Verapamil resulted in an increase in glucose and urea clearance. [6] The above-mentioned study also showed that Verapamil did not have any effects on creatinine clearance and urea Kt/V. However, the results of this study differed from the results of other studies. [7],[8] The above study has also shown that Verapamil does not possess any effects on glucose, creatinine, sodium, potassium and urea clearances, which is similar to other studies, [1],[8],[10],[11],[12] whereas other studies have shown that Enalapril increases the creatinine clearance significantly. [13] It was concluded in the Kumano study in 1996 that Captopril increases membrane permeability to small and large molecules. [6] This study showed that Enalapril significantly increases the peritoneal urea Kt/V and similarly decreases the mean arterial pressure and diastolic blood pressure, a result in accordance with other studies. [1] Inhibition of the RAAS in these patients leads to blockade of AgII effect, which is a strong vasoconstrictor agent. Inhibition of AgII by drugs results in decreased Kinin degradation, stimulation of vasodilator prostaglandins and decrease in sympathetic system activity. [1]

Moreover, Enalapril results in increased peritoneal creatinine transportation speed. Enalapril has a direct influence on mesothelial and vascular resistance and leads to increased overall splanchnic blood flow, resulting in increased mesenteric blood volume and blood flow [13] and leading to increased peritoneal permeability. It has been shown in some studies that ACE-I results in an increased clearance of small and large molecules. [6]

Low sample volume may be one of the reasons for discordance of the results in this study in comparison with other studies. Majority of the PD patients in our country are negatively selected and were excluded from the study mainly because of cardiac diseases.

The strength of this study is the study type (cross-over clinical trial), in which the patient is compared with himself; therefore, other biascreating factors such as age, sex, race and biologic/pharmacologic factors are eliminated.

In conclusion, this study has shown that oral Enalapril results in a significant increase in peritoneal urea Kt/V; moreover, it causes a meaningful decrease in the diastolic and mean blood pressures. Therefore, Enalapril can be administered as an anti-hypertensive medication of choice in CAPD patients who do not have a suitable dialysis adequacy. However, studies with larger sample sizes are needed in the future to further evaluate these findings.

 
   References Top

1.Ripley EB, Gehr TW, Kish CW, Sica DA. Hormonal blood pressure & peritoneal transport response to short-term ACE-inhibition. Perit Dial Int 1994;14:378-83.  Back to cited text no. 1
[PUBMED]    
2.Wu G, Wieczorowska-Tobis K, Polubinska A, et al. N-acetylglucoseamin changes permeability of peritoneum during chronic PD in rats. Perit Dial Int 1998;18:217-40.  Back to cited text no. 2
[PUBMED]    
3.Thitiarchakuls S, Lal SM, Moore HL, Nolph KD. Effect of cholorpromazin or diltiazem given intraperitoneally alone or in combination on peritoneal transport of solute & water. Adv Perit Dial 1999;15:7-11.  Back to cited text no. 3
    
4.Douma CE, Hiralall JK, de Waart DR, Struijk DG, Krediet RT. Icodextrin with Nitroprusside Increases Ultrafiltration & Peritoneal Transport During Long CAPD Dwells. Kidney Int 1998; 53:1014-21.  Back to cited text no. 4
[PUBMED]    
5.El-Sherif AK, Rizkalla NH, Essawy MH, El-Gohary AM. Minoxidil selectively improves peritoneal ultrafiltration. Perit Dial Int 1996; 16(Suppl 1):S91-4.  Back to cited text no. 5
[PUBMED]    
6.Kumano K, Go M, Ning H, Sakai T. Effects of vasodilators on peritoneal solute & fluid transport in rat peritoneal dialysis. Adv Perit Dial 1996;12:27-32.  Back to cited text no. 6
[PUBMED]    
7.Vargemezis B, Pasadakis P, Thodis E. The effect of calcium antagonists on the peritoneal membrane in patients on CAPD. Adv Perit Dial 1989;5:8-11.  Back to cited text no. 7
    
8.Rojas-Campos E, Cortes-Sanabria L, Martines-Ramires HR, et al. Effect of oral adminstration of losartan, prazosin & verapamil on peritoneal solute transport in CAPD patients. Perit Dial Int 2005;25:576-82.  Back to cited text no. 8
    
9.Oreopoulos DG. The optimization of continuous ambulatory peritoneal dialysis. Kidney Int 1999;55:1131-49.  Back to cited text no. 9
[PUBMED]    
10.Breborowicz A, Tobis KW, Korybalska K, Polubinska A, Radkowski M, Oreopoulos DG. The effect of a nitric oxide inhibitor (L-NAME) on peritoneal transport during dialysis in rats. Perit Dial Int 1998;18:188-92.  Back to cited text no. 10
    
11.Spaia S, Magoula I, Tsapas G, Vayonas G. Effect of pyrazinamide & probenecid on peritoneal urate transport kinetics during continuous ambulatory peritoneal dialysis. Perit Dial Int 2000;20:47-52.  Back to cited text no. 11
[PUBMED]    
12.Park MS, Lee EY, Lee NS, Waniewski J, Lindholm B, Lee HB. The effects of ouabain & potassium on peritoneal fluid & solute transport characteristics. Perit Dial Int 1998;18:402-9.  Back to cited text no. 12
[PUBMED]    
13.Favazza A, Montanaro D, Messa P, Antonucci F, Gropuzzo M, Mioni G. Peritoneal clearances in hypertensive CAPD patients after oral administration of clonidine, enalapril & nifedipine. Perit Dial Int 1992;12:287-91.  Back to cited text no. 13
    

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Correspondence Address:
Shahnaz Atabak
Imam Khomeini Hospital, Razi Street, Sari
Iran
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DOI: 10.4103/1319-2442.121274

PMID: 24231479

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