The Role of Cytokines in Nephrotic Syndrome

Table 1

Summary of articles evaluated the levels of cytokines in clinical samples of patients with SRNS.

		Participants	Age	Sample	Cytokines	Results	Ref.
1	Children	SS: 26; SR: 14	SS: SR:	Plasma	A panel of 27 cytokines	In children with new-onset NS, glucocorticoid therapy decreases the levels of plasma cytokines secreted by CD8^+, CD4^+ TH1, and TH2 cells. Moreover, MCP-1, IL-9, and L-7 could predict SRNS prior to glucocorticoid therapy at disease presentation.	[28]
2	Children	C: 20; SS: 19; SR: 7	C:SS: SR:	Saliva	IL-1β, IL-4, IL-6, IL-8, and IFN-γ	The studied cytokines were not able to discriminate SRNS from SSNS or the relapse from remission states.	[40]
3	Children	SS: 29; SD: 24; SR: 9	SS: 4.3 (2–11); SD: 3.2 (1–13); SR: 8.5 (2–17)	Plasma	48 cytokines	Plasma levels of MIF can identify cases at high risk of SRNS. A cutoff MIF concentration of more than 501 pg/ml could discriminate SRNS cases with 71.4% specificity and 85.7% sensitivity.	[48]
4	Children	Remission: 9; SS: 6; SR: 4	5.9 (3.0–14.4)	PBMCs	18551 genes	In the SSNS group, the gene expression profile was enriched in genes relating to TGF-β1 signaling, IL-4 and IL-6, targets of FoxP3 in T lymphocytes, p53 signaling, and the cell cycle.	[21]
5	Children	C: 12; SR:12; SS: 12	C: SR: SS:	Kidney and urine	TGF-1, ICAM-1	TGF-1 in urine could differentiate between MCD and FSGS; however, it was not a biomarker of steroid responsiveness.	[19]
6	Children	C: 15; NS: 42	—	Serum	IL-13, TNF-β	A different Th2/Th1 reaction demonstrated by an imbalance of IL-13/TNF-β could play a pathophysiologic role in NS. SRNS and SSNS cases had, respectively, a higher serum TNF-β and IL-13 level after glucocorticoid therapy than that before treatment.	[29]
7	Children	C: 10; SR: 20; SS: 34	SR: 11.3 (4–17); SS: 10.5 (4–16)	Plasma	IL-20, IL-4R, IL-6ST, JUN, MPL, MYC, SP1 and SRC, SOCS1-5	In SRNS cases, levels of IL-20, IL-6, SOCS5, and SOCS3 were elevated after 6 weeks of treatment with steroids compared to control and SSNS groups. Increased expressions of SOCS3 and SOCS5 mRNAs may predict early resistance to steroids.	[56]
8	Children	C: 5; SR: 8; SS: 8	—	CD4^+ T cell	IFN-c, NF-κB, AP-1	There were significant increase in IL-2 expression and decrease in the p65 subunit of NF-κB in T cells from SRNS patients.	[37]
9	Adults	SRNS/FSGS: 96		Serum, immortalized thermosensitive human podocytes (clone AB8/13)	TNF-α pathway genes	In podocytes of FSGS patients, activation of TNF-α pathway genes happens.	[54]
10	Adults	SS: 50; SR: 27	C: 50; SS: SR:		IL-6, IL-1, TNF, IFN-γ, CRP, suPAR, haemopexin, haptoglobin	Increased levels of IL-6, haemopexin, and haptoglobin are only associated with steroid resistance in a certain group of patients. In other cases, steroid resistance is clearly unrelated to an activated inflammatory response. Multivariate analyses indicated that the levels of these 3 inflammatory factors are independent predictors of SR.	[3]

C: control; SD: steroid dependent; SS: steroid sensitive, PBMCs: peripheral blood mononuclear cells; SRNS/FSGS: steroid-resistant nephrotic syndrome/Focal segmental glomerulosclerosis; MCD: minimal change disease; TNF-α: tumor necrosis factor-α; IFN-γ: interferon-gamma; NF-κB: nuclear factor-κB; AP-1: activating protein-1; IL-6: interleukin-6; suPAR: soluble urokinase-type plasminogen activator receptor; CRP: C-reactive protein.