Plasma levels of IL-1β, TNFα and their specific inhibitors in undialyzed chronic renal failure, CAPD and hemodialysis patients

Pereira, Brian J.G.; Shapiro, Leland; King, Andrew J.; Falagas, Matheos E.; Strom, James A.; Dinarello, Charles A.

doi:10.1038/ki.1994.117

Cited by 366 publications

(225 citation statements)

References 43 publications

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“…In addition and confirming previous results, the present study shows that CKD is associated with an inflammatory state, because the patients presented high levels of inflammatory biomarkers (30,31). This inflammatory state also could explain the high incidence of atherosclerotic complications in patients with CKD because atherosclerosis is considered a chronic vascular inflammatory disorder (32). Although in comparison with healthy control subjects with normal renal function, no changes were observed in the median plasma levels of adipokines (leptin or adiponectin) considering the whole group of patients with CKD, however, patients with stage 4 CKD (eGFR Ͻ30Ͼ15 ml/min) had significant higher adiponectin levels than control subjects with normal renal function.…”

Section: Discussionsupporting

confidence: 75%

Insulin Resistance, Inflammatory Biomarkers, and Adipokines in Patients with Chronic Kidney Disease

Vinuesa

Goicoechea

Kanter

et al. 2006

Journal of the American Society of Nephrology

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Patients with chronic kidney disease (CKD) present a high prevalence of insulin resistance (IR). Some studies suggest that angiotensin II may influence some cellular pathways that contribute to the pathogenesis of IR and stimulate the release of proinflammatory cytokines. Fifty-two patients who had stages 3 and 4 CKD and no diabetes were administered an angiotensin receptor blocker (ARB), olmesartan (40 mg), for 16 wk. Before and after ARB treatment, metabolic and inflammatory parameters and adipokines were measured. IR was calculated by Homeostasis Model Assessment (HOMA) index. Baseline data were compared with data that were obtained from 25 healthy control individuals of similar age and normal renal function. Compared with control subjects, patients with CKD presented significantly higher BP and waist circumference, higher triglycerides and lower HDL levels, higher insulin levels, and higher mean HOMA index (6.0 ؎ 2.7 versus 2.9 ؎ 2.2 U/ml ؋ mmol/L; P < 0.001). In addition, patients with CKD had increased levels of high-sensitivity C-reactive protein, TNF-␣, and IL-6. In patients with CKD, leptin was positively correlated to abdominal obesity, insulin levels, and IL-6, and adiponectin was inversely correlated to abdominal obesity and insulin levels. Olmesartan treatment resulted in a significant decrease of BP, urinary protein excretion, plasma glucose (99 ؎ 16 versus 92 ؎ 14 mg/dl; P < 0.05), insulin (23.1 ؎ 8.8 versus 19.9 ؎ 9; P < 0.05), HOMA index (6.0 ؎ 2.7 versus 4.7 ؎ 2.8; P < 0.05), and glycated hemoglobin (5.33 ؎ 0.58 versus 4.85 ؎ 0.81%; P < 0.01). At the same time, there was a significant reduction of high-sensitivity C-reactive protein levels, from 4.45 mg/L (2.45 to 9.00) to 3.55 mg/L (1.80 to 5.40; P < 0.05) and fibrinogen (412 ؎ 100 versus 370 ؎ 105 mg/dl; P < 0.05). There were no significant differences in adipokine levels after olmesartan treatment. These data demonstrate that patients with CKD have a high prevalence of IR, metabolic syndrome, and chronic inflammation and that the administration of the ARB olmesartan improves IR and inflammation markers in these patients. Plasma adipokine levels that are related to several metabolic risk factors in patients with CKD were not modified by ARB therapy.

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Section: Discussionsupporting

confidence: 75%

Insulin Resistance, Inflammatory Biomarkers, and Adipokines in Patients with Chronic Kidney Disease

Vinuesa

Goicoechea

Kanter

et al. 2006

Journal of the American Society of Nephrology

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“…[1][2][3][4]13,14 Sonkar ve ark., KBY hastalarında TNF-α düzeylerinin sağlıklı kontrollere göre daha yüksek olduğunu göstermişlerdir. 6 Ayrıca, Yeo ve ark.…”

Section: Discussionunclassified

Relationship Between Serum Tumor Necrosis Factor-Alpha Levels and Insulin Resistance in Patients with Chronic Renal Failure

Ulaş¹,

Baştürk²,

Şakacı³

et al. 2012

Turkiye Klinikleri J Med Sci

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Ö ÖZ ZE ET T A Am ma aç ç: : Kronik böbrek yetersizliği, sitokin düzensizliğinin olduğu kronik mikroenflamatuar bir süreçtir ve artmış insülin direnci de bu hastalarda bilinen bir durumdur. Tüber nekroz faktörü (TNF)-α da proinflamatuar bir sitokindir ve bunun kronik böbrek yetersizliği hastalarında artmış olduğu bazı çalışmalarda gösterilmiştir. Biz de bu çalışmayı, kronik böbrek yetersizliği hastalarında serum TNF-α düzeylerini, insülin direnci değerlerini ve bunların birbirleriyle olan ilişkisini araştır-mak amacıyla planladık. G Ge er re eç ç v ve e Y Yö ön nt te em ml le er r: : Çalışmaya 15'i kadın, kronik böbrek yetersizliği olan 30 hasta (grup 1), kontrol grubu olarak 16'sı kadın 30 sağlıklı kişi (grup 2) olacak şekilde, toplam 60 hasta alındı. Hastalarda serum kreatinin, glomerüler filtrasyon hızı, TNF-α, açlık kan şekeri, açlık insülin düzeyleri çalışıldı ve HOMA-IR düzeyleri hesaplandı. B Bu ul lg gu ul la ar r: : Glomerüler filtrasyon hızı değerleri ortalamaları grup 1 için 42,05 ± 24,60 ml/dk ve grup 2 için 106,67 ± 17,10 ml/dk, TNF-α değerleri sırasıyla grup 1 için 57,65 ± 42,2 pg/ml ve grup 2 için 18,25 ± 7,90 pg/ml olarak HOMA-IR değerleri grup 1 için 3,71 ± 2,56 ve grup 2 için 2,37 ± 1,45 olarak saptandı. Grup 1 ve grup 2'nin HOMA-IR ve TNF-α düzeyleri sırasıyla karşılaştırıldığında istatistiksel olarak anlamlı fark saptandı (p< 0,01) (p< 0,001). Ancak TNF-α ile HOMA-IR'nin ikili korelasyonunda negatif veya pozitif yönlü ilişki saptanamadı (r= 0,091, p= 0,634). Yapılan regresyon analizinde TNF-α kronik böbrek yetersizliğinde bağımsız bir değişken olarak tespit edildi (p= 0,010). S So on nu uç ç: : Bu çalışmada, kronik böbrek yetersizliği olgularında insülin direnci bulunduğu ve dolaşımdaki TNF-α düzeyinin böbrek yetersizliği olmayan kontrollere göre daha yüksek olduğu fakat TNF-α'nın insülin direncine etki etmediği tespit edilmiştir.A An na ah ht ta ar r K Ke el li im me el le er r: : İnsülin direnci; böbrek yetmezliği, kronik; tümör nekroze edici faktör-alfa A AB BS ST TR RA AC CT T O Ob bj je ec ct ti iv ve e: : Chronic renal failure is a chronic microinflammatory process of cytokine dysregulation and increased insulin resistance is a known concept in these patients. Tumor necrosis factor (TNF)-α is a proinflammatory cytokine and has been shown to increase in chronic renal failure patients in some studies. We planned this study to investigate TNF-α levels, insulin resistance values and interrelations in chronic renal failure patients. M Ma at te er ri ia al l a an nd d M Me et th ho od ds s: : A total of 60 subjects of whom 30 had chronic renal failure (15 females-group 1) and 30 were healthy controls (16 females-group 2) were included in the study. Serum creatinine, glomerular filtration rate levels, TNF-α, fasting plasma glucose, fasting insulin levels were studied and HOMA-IR was calculated. R Re es su ul lt ts s: : Mean values of glomerular filtration rate were detected as follows; group 1: 42.05 ± 24.60 ml/min and group 2: 106.67 ± 17.10 ml/min, TNF-α values were found as group1:57.65 ± 4...

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“…The process of dialysis is also known to cause increases in some cytokines such as TNF-a although changes induced by dialysis vary with the type of membranes used (Cavaillon et al, 1992;Jorres et al, 1992;Nakahama et al, 1992;Ward and Gordon, 1993;Canivet et al, 1994;Halwachs et al, 1994;Leeuwenberg et al, 1994;Pereira et al, 1994). This probably accounts for the higher TNF-a concentrations seen in the anephric patient before treatment with IL-2.…”

Section: Discussionmentioning

confidence: 99%

Treatment of metastatic renal cell carcinoma with subcutaneous interleukin 2: evidence for non-renal clearance of cytokines

Banks

Forbes²,

Hallam³

et al. 1997

Br J Cancer

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Summary The circulating cytokine concentrations following administration of subcutaneous recombinant interleukin 2 (IL-2) in combination with interferon a and 5-fluorouracil used to treat advanced renal cancer were studied. One patient was anephric and on dialysis, and seven had normal biochemical renal function, although five had undergone single nephrectomy. The pharmacokinetics of IL-2 and changes in IL-6 and tumour necrosis factor (TNF)-a were essentially similar in all patients including the anephric patient, irrespective of the periods of dialysis, although at some time points, IL-2 concentrations were slightly higher in the anephric patient than in the others. These results show that for subcutaneous administration of low-dose IL-2, renal clearance of IL-2 is not important. This contrasts with high-dose, intravenous IL-2 where blood concentrations are higher and renal clearance seems to occur, perhaps because of saturation of the non-renal mechanisms of clearance. The subcutaneous route is certainly preferred if IL-2 is used in anephric patients and in those with impaired renal function, and it may be generally preferred for most purposes.Keywords: interleukin 2; renal; anephric; cytokine; clearance; therapy The use of interleukin 2 (IL-2) as a biological anti-cancer therapy is based on its ability to activate and enhance the cytotoxic activity of T lymphocytes and to stimulate natural killer cell-and lymphokine-activated killer cell activity. These actions are probably mediated both directly and via secondary induction of a cascade of cytokines including tumour necrosis factor (TNF)-a and IL-6 (Whittington and Faulds 1993; Janssen et al, 1994). Multiple regimens with IL-2 have been developed, but progress has been hampered by the marked toxicity associated with many of the higher dose intravenous (i.v.) regimens employed, most notably a capillary leak syndrome (similar to that seen in patients with septic shock) manifest by hypotension, weight gain, acute renal failure and pulmonary oedema (Whittington and Faulds, 1993). Newer approaches using lower dose subcutaneous (s.c.) IL-2 have been promising with, for example, recent combination regimens producing objective responses with less accompanying toxicity in 30-40% of patients with metastatic renal cell carcinoma (Atzpodien et al, 1990;Atzpodien-et al, 1993;Joffe et al, 1996).An understanding of cytokine metabolism is important for ensuring a rational approach to the design of therapeutic strategies, particularly with regard to route of administration and dosage. The mechanism of clearance is an important consideration as IL-2, for example, may be administered to patients who have undergone a nephrectomy, occasionally bilateral nephrectomies, and IL-2 itself may cause renal dysfunction. The Correspondence to: RE Banks following i.v. administration is generally thought to be consistent with a two-compartment model with first-order elimination kinetics. In rodents, an initial rapid clearance with a half-life (t,2) of approximately 1-5 min is followed by ...

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Plasma levels of IL-1β, TNFα and their specific inhibitors in undialyzed chronic renal failure, CAPD and hemodialysis patients

Cited by 366 publications

References 43 publications

Insulin Resistance, Inflammatory Biomarkers, and Adipokines in Patients with Chronic Kidney Disease

Insulin Resistance, Inflammatory Biomarkers, and Adipokines in Patients with Chronic Kidney Disease

Relationship Between Serum Tumor Necrosis Factor-Alpha Levels and Insulin Resistance in Patients with Chronic Renal Failure

Treatment of metastatic renal cell carcinoma with subcutaneous interleukin 2: evidence for non-renal clearance of cytokines

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