To the Editor,
It is well known that certain calcium channel blockers (CCB) can cause cloudy peritoneal fluid not associated to infection (NICPF).
We report what we believe to be the first case of cloudy peritoneal fluid in relation to lercanidipine identified in our country and possibly in Europe.
CASE REPORT
The patient was a 59-year-old Caucasian female with chronic renal failure secondary to mesangial proliferative glomerulonephritis. She had high blood pressure and was on treatment with 320mg/day valsartan and 4mg/day doxazosin and was on peritoneal dialysis. She presented with cloudy peritoneal fluid. She did not complain of abdominal pain, fever or any other abdominal symptoms. Three days previously, 5mg/day lercanidipine had been added to her treatment. The appearance of the peritoneal fluid was milky and it did not contain fibrin. The cell count in the dialysate and the subsequent culture were negative. Plasma values for cholesterol and triglycerides (TG) were 189 and 175mg/dl, respectively and the dialysate value for TG was 20mg. Having ruled out bacterial peritonitis and given the potential relationship with lercanidipine, this drug was discontinued and 24 hours later, clear dialysate drainage was confirmed.
A few weeks later, the patient changed to automated peritoneal dialysis with a dry day, and with her consent, 5mg/day lercanidipine was reintroduced into her night dose.
One month later, she presented again with cloudy fluid without associated symptoms. Again, the cell count and culture of the dialysate were negative. On this occasion, TG was not measured in dialysate, but its plasma value was 145mg/dl (lower than in the previous episode). With the diagnosis of NICPF related to CCB, lercanidipine was discontinued. Again, the dialysate became clear over the next few hours.
DISCUSSION
NICPF is uncommon in peritoneal dialysis and its occurrence obliges us to carry out a differential diagnosis that must distinguish between clinical profiles with an increase in cellularity and acellular causes1,2. The absence of cells rules out infection, inflammation, allergic reaction and bleeding. Fibrin, TG and drugs have been reported as the most common causes of acellular NICPF
CCB are amongst the drugs included. The oldest case was published in 1993 in relation to manidipine3, the drug most commonly involved, although other CCB, most of them dihydropyridines, can also trigger it4. Since the appearance of new CCB, cases of secondary NICPF have been published fairly frequently.5,6. Curiously, classic types of CCB do not cause it or do so less frequently7. This has led us to believe that the characteristics of the different CCB may influence the occurrence of NICPF.
CCB-induced NICPF is defined as4: cloudiness of the dialysate that appears 48-72 hours after the administration of the drug, with the absence of peritoneal inflammatory signs and symptoms and a negative cell count and peritoneal fluid culture, which disappears spontaneously after the drug is discontinued. Unlike infectious peritonitis, some authors have noted an increase in ultrafiltration during the episode8.
The cloudiness of the peritoneal fluid, which is characteristically milky, is due to the presence of TG (normally almost non-existent in the dialysate if there is no other cause), although they do not always reach chyloperitoneum levels (>100mg/dl). The mechanism whereby TG increase is still unknown, although there has been speculation that it may be due to a disorder of its degradation in the peritoneum or the reduction of lymphatic stomata in the diaphragmatic peritoneum3,8. It has been noted that TG in dialysate seem to have a direct relationship with TG levels in blood9. Lercanidipine acts both in the smooth muscle cells of blood vessels and of the lymphatic system and the digestive tract, which may explain its effect9.
Reports of NICPF secondary to lercanidipine have a curious geographic distribution: the few cases reported have occurred in Asia8-10, and the closest to Europe are located in the Asian region of Turkey11. Although it has been much used in Europe for years, we have not found reported cases of NICPF related to its use (in contrast to the high incidence of cases related to manidipine). This has made us consider that racial factors or genetic predisposition may be involved8,9.
Apart from the unsettling effect, the presence of NICPF does not seem to have any negative clinical repercussions. In fact, Yang reported two patients who remained on lercanidipine in whom the cloudiness gradually disappeared9.
In our case, all the data support our diagnosis of NICPF secondary to lercanidipine. In the second episode, the delay in the reappearance of peritoneal cloudiness was surprising, which we thought could be related to the absence of dialysate in the peritoneal cavity during the daytime.
In summary, in the presence of acellular NICPF, we must rule out the potential relationship with CCB in order to avoid unnecessary antibiotic treatment.
Conflicts of interest
The authors declare that they have no conflicts of interest related to the contents of this article.
