Clinical significance of granulocyte‐inhibiting proteins

Haag–Weber, Marianne; Cohen, Gary N.; Hörl, Walter H.

doi:10.1093/oxfordjournals.ndt.a027957

Cited by 25 publications

(22 citation statements)

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“…25 Several granulocyte-inhibitory proteins retained in uremic patients-contributing to the high incidence of infectionscould be better removed with OL-HDF therapies. 26 OL-HDF was also associated with a significant reduction in hospitalization rates, which could reasonably be linked to the decrease in cardiovascular and infectious complications. Clearance of middle-to-large molecules depends on the type of dialysis membrane and the amount of convection volume and may be increased with OL-HDF treatment.…”

Section: Discussionmentioning

confidence: 95%

High-Efficiency Postdilution Online Hemodiafiltration Reduces All-Cause Mortality in Hemodialysis Patients

Maduell

Moreso

Pons³

et al. 2013

Journal of the American Society of Nephrology

619

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Retrospective studies suggest that online hemodiafiltration (OL-HDF) may reduce the risk of mortality compared with standard hemodialysis in patients with ESRD. We conducted a multicenter, open-label, randomized controlled trial in which we assigned 906 chronic hemodialysis patients either to continue hemodialysis (n=450) or to switch to high-efficiency postdilution OL-HDF (n=456). The primary outcome was all-cause mortality, and secondary outcomes included cardiovascular mortality, all-cause hospitalization, treatment tolerability, and laboratory data. Compared with patients who continued on hemodialysis, those assigned to OL-HDF had a 30% lower risk of all-cause mortality (hazard ratio [HR], 0.70; 95% confidence interval [95% CI], 0.53-0.92; P=0.01), a 33% lower risk of cardiovascular mortality (HR, 0.67; 95% CI, 0.44-1.02; P=0.06), and a 55% lower risk of infection-related mortality (HR, 0.45; 95% CI, 0.21-0.96; P=0.03). The estimated number needed to treat suggested that switching eight patients from hemodialysis to OL-HDF may prevent one annual death. The incidence rates of dialysis sessions complicated by hypotension and of all-cause hospitalization were lower in patients assigned to OL-HDF. In conclusion, high-efficiency postdilution OL-HDF reduces all-cause mortality compared with conventional hemodialysis.

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Section: Discussionmentioning

confidence: 95%

High-Efficiency Postdilution Online Hemodiafiltration Reduces All-Cause Mortality in Hemodialysis Patients

Maduell

Moreso

Pons³

et al. 2013

Journal of the American Society of Nephrology

619

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“…A critical role in the pathogenesis of increased susceptibility to infections is exerted by functional abnormalities of neutrophils (24,40). These dysfunctions are considered secondary to diverse causes, such as accumulation of calcium within the cells, iron overload, interactions with biocompatible dialyzers and dialysis solutions, and several uremic molecules including low molecular weight proteins (LMWP) (25,26,40). LMWP are a recently categorized class of proteins that have a MW spectrum ranging from 1,000 to 50,000 Da and are thought to be crucial for the pathogenesis of uremic syndrome, including malnutrition and increased susceptibility to infections (21,41).…”

Section: Discussionmentioning

confidence: 99%

“…LMWP are a recently categorized class of proteins that have a MW spectrum ranging from 1,000 to 50,000 Da and are thought to be crucial for the pathogenesis of uremic syndrome, including malnutrition and increased susceptibility to infections (21,41). As far as neutrophil function is regarded, six so-called granulocyte-inhibiting proteins (GIP) have been purified from ultrafiltrate of dialyzers and peritoneal effluent (26). GIP exert their inhibitory activity toward different functional activities of neutrophils, including oxidative metabolism, chemotaxis, degranulation, and phagocytosis, with consequent impairment of neutrophil-dependent antibacterial defense (21,26).…”

Section: Discussionmentioning

confidence: 99%

“…As far as neutrophil function is regarded, six so-called granulocyte-inhibiting proteins (GIP) have been purified from ultrafiltrate of dialyzers and peritoneal effluent (26). GIP exert their inhibitory activity toward different functional activities of neutrophils, including oxidative metabolism, chemotaxis, degranulation, and phagocytosis, with consequent impairment of neutrophil-dependent antibacterial defense (21,26). Also, leptin has been categorized as a LMWP, and, indeed, a role for this protein in some uremic manifestations, such as anorexia and weight loss, has been suggested (21,41).…”

Section: Discussionmentioning

confidence: 99%

“…In agreement with this observation, another hyperleptinemic condition, obesity (22), is also associated with an increased incidence of infections (23). As far as ESRD is concerned, it is generally assumed that the defects in phagocytic polymorphonuclear neutrophilic leukocytes (neutrophils) plays a crucial role in the infectious morbidity (24), and, indeed, several uremic toxins (e.g., molecules that are capable of depressing neutrophil functions) have been identified (25,26). Despite active investigations regarding other immune cells, only a few reports about leptin and neutrophils are available.…”

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confidence: 85%

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Leptin as a Uremic Toxin Interferes with Neutrophil Chemotaxis

Ottonello¹,

Gnerre²,

Bertolotto³

et al. 2004

Journal of the American Society of Nephrology

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Abstract. Leptin is a pleiotropic molecule involved in energy homeostasis, hematopoiesis, inflammation, and immunity. Hypoleptinemia characterizing starvation has been strictly related to increased susceptibility to infection secondary to malnutrition. Nevertheless, ESRD is characterized by high susceptibility to bacterial infection despite hyperleptinemia. Defects in neutrophils play a crucial role in the infectious morbidity, and several uremic toxins that are capable of depressing neutrophil functions have been identified. Only a few and contrasting reports about leptin and neutrophils are available. This study provides evidence that leptin inhibits neutrophil migration in response to classical chemoattractants. Moreover, serum from patients with ESRD inhibits migration of normal neutrophils in response to N-formyl-methionyl-leucyl-phenylalanine with a strict correlation between serum leptin levels and serum ability to suppress neutrophil locomotion.Finally, the serum inhibitory activity can be effectively prevented by immune depletion of leptin. The results also show, however, that leptin by itself is endowed with chemotactic activity toward neutrophils. The two activities-inhibition of the cell response to chemokines and stimulation of neutrophil migration-could be detected at similar concentrations. On the contrary, neutrophils exposed to leptin did not display detectable [Ca 2ϩ

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The First 2 Years of Biosimilar Epoetin for Cancer and Chemotherapy-Induced Anemia in the U.S.: A Review from the Southern Network on Adverse Reactions

et al. 2021

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Biosimilars are biologic drug products that are highly similar to reference products in analytic features, pharmacokinetics and pharmacodynamics, immunogenicity, safety, and efficacy. Biosimilar epoetin received Food and Drug Administration (FDA) approval in 2018. The manufacturer received an FDA nonapproval letter in 2017, despite receiving a favorable review by FDA's Oncologic Drugs Advisory Committee (ODAC), and an FDA nonapproval letter in 2015 for an earlier formulation. We discuss the 2018 FDA approval, the 2017 FDA ODAC Committee review, and the FDA complete response letters in 2015 and 2017; review concepts of litigation, naming, labeling, substitution, interchangeability, and pharmacovigilance; review European and U.S. oncology experiences with biosimilar epoetin; and review the safety of erythropoiesis-stimulating agents. In 2020, policy statements from AETNA, United Health Care, and Humana indicated that new epoetin oncology starts must be for biosimilar epoetin unless medical need for other epoetins is documented. Empirical studies report that

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Clinical significance of granulocyte‐inhibiting proteins

Cited by 25 publications

References 0 publications

High-Efficiency Postdilution Online Hemodiafiltration Reduces All-Cause Mortality in Hemodialysis Patients

High-Efficiency Postdilution Online Hemodiafiltration Reduces All-Cause Mortality in Hemodialysis Patients

Leptin as a Uremic Toxin Interferes with Neutrophil Chemotaxis

The First 2 Years of Biosimilar Epoetin for Cancer and Chemotherapy-Induced Anemia in the U.S.: A Review from the Southern Network on Adverse Reactions

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