Effect of membrane composition on cytokine production and clinical symptoms during hemodialysis: a crossover study.
BACKGROUND
Intradialytic symptoms including hypotension have been reported during dialysis and it has been suggested that these are related to the release of cytokines like IL-1beta and TNFalpha by blood mononuclear cells when they get activated either due to contact with the dialyzer membrane or by compliment activation.


OBJECTIVE
To study the relationship between hemodialysis symptoms, cytokine production, and dialyzer membrane composition.


METHODS
In a randomized prospective crossover study, 20 ESRD patients on maintenance hemodialysis were studied over cuprophan (CU) and polysulfone (PS) low flux dialyzer membranes for three weeks each undergoing a biweekly dialysis schedule of 4 h sessions. Serial IL-1beta and TNFalpha levels were measured over 0, 15, 240 min during the first use of the dialyzer for all patients on both membranes. Intradialytic symptoms were monitored in a total of 240 dialysis sessions.


RESULTS
IL-1beta levels increased from 16.6 +/- 2.2 to 64.8 +/- 25.1 pg/mL on CU and 21.5 +/- 3.7 to 103.5 +/- 30.7 pg/mL on PS membrane over the 4-h dialysis session. Similarly TNFalpha increased from 42.8 +/- 4.5 to 354.9 +/- 80.4 pg/mL on CU and 117.1+/- 53.7 to 387.0 +/- 78.0 pg/mL on PS membrane. IL-1beta levels increased significantly with PS membrane while TNFalpha rise was significant with both the membranes. Nausea was the most common symptom occurring in 138 dialysis sessions (57.5%). Vomiting, chest pain, fever, chills, and breathlessness occurred significantly more during dialysis with CU membrane as compared with PS membrane (P < 0.01). Nausea, cramps, back pain, itching, restlessness, post dialysis fatigue, and hypotension did not differ between the two membranes. The mean rise in the cytokine levels during the first 15 min of sessions where the symptoms occurred, when compared with the mean rise in sessions where the symptoms did not occur, did not reveal any significant difference. Cytokine release did not correlate with the occurrence of intradialytic symptoms.


CONCLUSIONS
Both CU and PS membranes increase circulating cytokine levels. More intradialytic clinical symptoms are seen in dialysis with CU as compared with PS membrane but the rise in cytokines IL-1beta and TNFalpha does not appear to be responsible for them.
Singh
N P
NP
Department of Medicine, Nephrology Division, LNJP and GB PANT Hospitals, New Delhi, India. nanu_singh@yahoo.com
Bansal
Ravi
R
Thakur
A
A
Kohli
R
R
Bansal
R C
RC
Agarwal
S K
SK
D000293:Adolescent; D000328:Adult; D001672:Biocompatible Materials / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D002482:Cellulose / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018592:Cross-Over Studies; D016207:Cytokines / Q000096:biosynthesis* / Q000187:drug effects; D003928:Diabetic Nephropathies / Q000150:complications / Q000378:metabolism / Q000628:therapy; D005260:Female; D005921:Glomerulonephritis / Q000150:complications / Q000378:metabolism / Q000628:therapy; D006801:Humans; D006977:Hypertension, Renal / Q000150:complications / Q000378:metabolism / Q000628:therapy; D007375:Interleukin-1 / Q000378:metabolism; D007676:Kidney Failure, Chronic / Q000209:etiology / Q000378:metabolism / Q000628:therapy; D008297:Male; D008567:Membranes, Artificial; D008875:Middle Aged; D007690:Polycystic Kidney Diseases / Q000150:complications / Q000378:metabolism / Q000628:therapy; D011108:Polymers / Q000627:therapeutic use; D011446:Prospective Studies; D016032:Randomized Controlled Trials as Topic; D006435:Renal Dialysis; D013223:Statistics as Topic; D013450:Sulfones / Q000627:therapeutic use; D013997:Time Factors; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects / Q000378:metabolism
D001672:Biocompatible Materials; D015415:Biomarkers; D016207:Cytokines; D007375:Interleukin-1; D008567:Membranes, Artificial; D011108:Polymers; D013450:Sulfones; D014409:Tumor Necrosis Factor-alpha; C017662:polysulfone P 1700; D002482:Cellulose; C009865:cuprammonium cellulose