Soluble TNF-R1, VEGF and other cytokines as markers of disease activity in systemic lupus erythematosus and lupus nephritis.

BACKGROUND: Current non-invasive methods of assessing disease activity in systemic lupus erythematosus (SLE) are of limited sensitivity and specificity. Testing includes acute phase markers, autoantibodies and complement levels. Although measurements of dsDNA antibodies and complement C3/C4 levels are routine, they remain of limited value. Improved blood and urine markers may help in early detection of flare, distinction between flare and chronic damage, and monitoring response to therapy. METHODS: A total of 87 patients with SLE were tested for the following cytokines in serum and urine: monocyte chemoattractant protein 1 (MCP-1), regulated upon activation, normal T cell expressed and secreted (RANTES), soluble tumour necrosis factor receptor 1 (sTNF-R1), interferon-inducible protein 10 (IP-10), monocyte inhibitory protein 1α (MIP-1α) and vascular endothelial growth factor (VEGF). Patients attending the Lupus Unit at St Thomas' Hospital, London, UK were divided into active lupus nephritis (LN), inactive LN and non-renal SLE groups based on their renal pathology and SLE disease activity index (SLEDAI). Cytokine testing was performed using the FIDIS multiplex bead assay. RESULTS: The mean level of serum sTNF-R1 was higher in the active LN group compared with both inactive LN and non-renal SLE groups ( p < 0.001). For urine measurements there were significant differences between active LN and non-renal SLE for VEGF ( p = 0.016), after statistical correction for multiple testing. Both urinary and serum sTNF-R1 and IP-10 levels correlated with SLEDAI scores ( p < 0.001), while serum VEGF correlated weakly with SLEDAI ( p = 0.025). The optimum combination for differentiating active from inactive LN patients was serum VEGF, sTNF-R1, MCP-1 and glomerular filtration rate plus urinary sTNF-R1 and protein-creatinine ratio. CONCLUSION: These results indicate that for active LN, sTNF-R1 could be a useful serum cytokine marker, with potential for VEGF in the urine. This study has confirmed the ability of the multiplex bead technique to detect cytokines in a good analytical range, including very low and high levels, in both serum and urine. Combining serum and urine markers provided additional sensitivity in distinguishing active from inactive LN.

Expressions of mRNA for innate immunity-associated functional molecules in urinary sediment in immunoglobulin A nephropathy.

AIM: It has been reported that the innate immune system plays a pivotal role in the pathogenesis of immunoglobulin A nephropathy (IgAN). To explore non-invasive monitoring of disease activity in children with IgAN, we examined whether expressions of mRNA for innate immunity-associated functional molecules: CC ligand chemokine 5 (CCL5), fractalkine/CX3CL1, interferon-γ-induced protein 10 (IP-10), monocyte chemoattractant protein 1 (MCP-1), retinoic acid-inducible gene-I (RIG-I), and toll-like receptor 3 (TLR3) in urinary sediment from patients with IgAN correlate with histologic parameters. METHODS: Twenty consecutive children with IgAN and four children with thin basement membrane disease (serving as a non-inflammatory control) were enrolled in this pilot study. Urinary mRNA expressions of target genes were examined real-time quantitative polymerase chain reaction. RESULTS: The expressions of CCL5, fractalkine and RIG-I were significantly increased in IgAN (all P < 0.05). Although no significant correlation was observed between mRNA expressions of these three molecules and clinical parameters, such as levels of urinary protein excretion, degrees of occult blood in urine and serum albumin, the expression of fractalkine was significantly correlated with the histological activity index (P = 0.022) and the chronicity index (P = 0.005). Furthermore, intense glomerular immune activity of fractalkine was observed in biopsy specimens in patients with moderately to severe proliferative IgAN. CONCLUSION: Regional expression of fractalkine may be involved in the pathogenesis of childhood IgAN. Although our present findings remain preliminary, measurement of mRNA expression of fractalkine in urinary sediment could be used as a non-invasive method for predicting histologic severity in IgAN in children. Further studies of this issue are needed.

Elevated Urinary T Helper 1 Chemokine Levels in Newly Diagnosed Hypertensive Obese Children.

OBJECTIVE: Increasing evidence suggests that T helper (Th) cells play a significant role in the pathogenesis of hypertension. The aim of this study was to evaluate the effect of obesity and anti-hypertensive treatment on urinary Th1 chemokines. METHODS: The study groups consisted of three types of patients: hypertensive obese, healthy, and non-hypertensive obese. Pre-treatment and post-treatment samples of the hypertensive obese group and one sample from the other two groups were evaluated for urinary chemokine: regulated on activation, normal T cell expressed and secreted (RANTES), interferon-gamma-inducible protein 10 (IP10), and monokine induced by interferon-gamma (MIG). In the hypertensive obese group, urine microalbumin: creatinine ratio was examined before and after treatment. We recommended lifestyle changes to all patients. Captopril was started in those who could not be controlled with lifestyle changes and those who had stage 2 hypertension. RESULTS: Twenty-four hypertensive obese (mean age 13.1), 27 healthy (mean age 11.2) and 22 non-hypertensive obese (mean age 11.5) children were investigated. The pre-treatment urine albumin: creatinine ratio was positively correlated with pre-treatment MIG levels (r=0.41, p<0.05). RANTES was significantly higher in the pre-treatment hypertensive and non-hypertensive obese group than in the controls. The urinary IP10 and MIG levels were higher in the pre-treatment hypertensive obese group than in the non-hypertensive obese. Comparison of the pre- and post-treatment values indicated significant decreases in RANTES, IP10, and MIG levels in the hypertensive obese group (p<0.05). CONCLUSION: Th1 cells could be activated in obese hypertensive children before the onset of clinical indicators of target organ damage. Urinary RANTES seemed to be affected by both hypertension and obesity, and urinary IP10 and MIG seemed to be affected predominantly by hypertension.

Nuclear NF-κB p65 in peripheral blood mononuclear cells correlates with urinary MCP-1, RANTES and the severity of type 2 diabetic nephropathy.

AIMS: To investigate if nuclear NF-κB p65 expression in ex vivo isolated peripheral blood mononuclear cells correlates with urinary MCP-1 or RANTES and the severity of type 2 diabetic nephropathy. METHODS: According to their urinary albumin-to-creatinine ratio (uACR), 107 patients with type 2 diabetes (eGFR >60 ml/min) were divided into normal albuminuria group (DN0 group, 38 cases), microalbuminuria group (DN1 group, 38 cases), and macroalbuminuria group (DN2 group, 31 cases), compared with matched healthy normal control group (NC group, 30 cases). Nuclear NF-κB p65 protein expression levels in peripheral blood mononuclear cells were detected by western blotting. Real-time quantitative polymerase chain reaction was used to detect NF-κB p65 mRNA expression and ELISA assay was used to detect the levels of urinary MCP-1 and RANTES. RESULTS: Nuclear NF-κB p65 protein and NF-κB p65 mRNA expression levels in peripheral blood mononuclear cells, urinary MCP-1/Cr and RANTES/Cr were all significantly higher in all diabetes groups as compared with NC group. In particular, the increase of nuclear NF-κB p65 protein and NF-κB p65 mRNA expressions, urinary MCP-1/Cr and RANTES/Cr all correlated with the severity of type 2 diabetic nephropathy as indicated by the increase in uACR. Pearson correlation analysis indicated that both urinary MCP-1/Cr and RANTES/Cr were positively correlated with nuclear NF-κB p65 protein or NF-κB p65 mRNA levels. Stepwise multiple regression analysis showed that nuclear NF-κB p65 protein or NF-κB p65 mRNA was an independent variable for urinary MCP-1/Cr, and MCP-1/Cr and RANTES/Cr were two independent variables for uACR. CONCLUSION: Our research demonstrates that nuclear NF-κB p65 protein and mRNA expressions in ex vivo isolated peripheral blood mononuclear cells well correlate with urinary MCP-1/Cr, RANTES/Cr and the severity of type 2 diabetic nephropathy.

Epidermal growth factor and monocyte chemotactic peptide-1: potential biomarkers of urinary tract obstruction in children with hydronephrosis.

OBJECTIVE: Hydronephrosis is diagnosed in 0.5% of all newborns, and ureteropelvic junction obstruction (UPJO) is a common cause. The aim of this study was to test whether specific urinary cytokines can be used as UPJO biomarkers in children with hydronephrosis. MATERIALS AND METHODS: Twenty-eight children referred for pyeloplasty due to UPJO and 13 controls were included in this prospective study. Kidney function was assessed and urine samples collected pre-, peri-, and post-operatively. Urine levels of epidermal growth factor (EGF), monocyte chemotactic peptide-1 (MCP-1), macrophage inflammatory protein-1α (MIP-1α), interferon-γ-inducible protein-10 (IP-10), and RANTES were measured simultaneously by using a bead-based multiplex sandwich immunoassay. RESULTS: In hydronephrotic children, preoperative urine levels were significantly increased for EGF (median 7.4 [1.2-60.2] vs. median 4.0 [1.2-13.8] ng/mg creatinine) and MCP-1 (median 136.9 [47.7-545.5] vs. median 80.1 [28.8-149.9] pg/mg creatinine) compared to those of controls. Urine levels of EGF and MCP-1 were identical to controls at the postoperative 1-year follow-up exam. CONCLUSION: Urine levels of EGF and MCP-1 were preoperatively increased and postoperatively normalized. This study demonstrates that urine-excreted kidney cytokines may be potential biomarkers of obstruction in children with hydronephrosis.

Urinary cytokine profiles in unilateral congenital hydronephrosis.

BACKGROUND: We aimed to evaluate possible clinical application of urinary monocyte chemotactic protein-1 (MCP-1), osteopontin (OPN), and regulated upon activation, normal T-cell expressed and secreted (RANTES) chemokine as useful noninvasive markers in children with congenital hydronephrosis (HN) caused by ureteropelvic junction obstruction (UPJO). METHODS: The study cohort consisted of surgical cases (study group 1), comprising 15 children with severe HN who required surgery (median age 1.03 years), conservative cases (study group 2), comprising 21 patients with mild, nonobstructive HN, and control group, comprising 19 healthy children. All children had normal renal function. Urinary (u) concentrations of MCP-1, OPN, and RANTES were measured using immunoenzymatic enzyme-linked immunosorbent assay (ELISA) commercial kits and were expressed in nanograms per milligram creatinine. Increased levels of MCP-1 and OPN were found in children with HN in comparison with study group 2 and controls (p < 0.05). UMCP-1/Cr correlated with half-time (T(1/2)) of the elimination phase of tracer excretion of technetium-99m-mercaptoacetyltriglycine ((99m)Tc-MAG-3) (p < 0.05). RESULTS: Receiver operator characteristic (ROC) analyses revealed good diagnostic profile for uMCP-1 only in identifying children (<40 %) with abnormal differential renal function (DRF) [area under the curve (AUC) 0.862], and in detecting kidney injury in all examined children (AUC 0.704). CONCLUSIONS: Additional studies with larger number of patients are required to confirm a potential application of uMCP-1 as a promising parameter for early identification of kidney obstruction.

Aberrant cytokines/chemokines production correlate with proteinuria in patients with overt diabetic nephropathy.

BACKGROUND: Diabetic nephropathy (DN) occurs in 20% to 30% of all patients with type 2 diabetes mellitus (DM) and is the most common cause of end-stage renal disease. However, the definite pathogenesis, especially the role of immune response, is still unclear. METHODS: We studied the production and expression of Th1 (IFN-gamma, IL-2R), Th2 (IL-4, IL-10), proinflammatory cytokines (IL-1beta, and TNF-alpha), and chemokines (MCP-1, and RANTES) in patients with DN. The correlation among cytokines, chemokines, and clinical parameters were examined. RESULTS: A patient with DN presented with longer disease duration, heavy proteinuria, and impaired renal function. Our results demonstrated increased proinflammatory cytokines, Th1 cytokines and chemokines, but not Th2 cytokines, in the plasma and urine of patients with DN as compared to patients with DM without overt nephropathy. Enhanced cytokine/chemokine activation in DN was also demonstrated by positive immunohistochemical staining of kidney tissue. We found a positive correlation between daily protein loss and plasma IFN-gamma and IL-2R, and urinary MCP-1, as well as a negative correlation between creatinine clearance and plasma TNF-alpha and urinary MCP-1. CONCLUSIONS: There were aberrant cytokines/chemokines production correlated with the degree of proteinuria in patient with overt DN and gross proteinuria. Inflammation may be important in the pathogenesis of DN.

Immune mediators in idiopathic nephrotic syndrome: evidence for a relation between interleukin 8 and proteinuria.

The pathogenesis of idiopathic nephrotic syndrome (INS) remains unknown. Several findings suggest a role for the immune system. This study aimed to evaluate immune mediators in INS by measuring plasma and urinary levels of transforming growth factor beta1 (TGF-beta1), monocyte chemoattractant protein-1 (MCP-1/CCL2), regulated on activation normal T-cell expressed and secreted (RANTES/CCL5) and IL-8 (IL-8/CXCL8) in pediatric patients with INS and in age-matched healthy controls. Patients were divided according to their response to corticosteroids: steroid-sensitive (SS, n = 8), or steroid-resistant (SR, n = 24). Immune mediators were also compared in regard with disease activity (relapse and remission). Immune mediators were measured by ELISA. Plasma TGF-beta1 levels in SR patients were approximately 2.8-fold higher than control values (p < 0.05). Urinary IL-8/CXCL8 was 2.9-fold higher in INS patients in relapse (proteinuria >100 mg/m2/24 h) when compared with patients in remission (p < 0.05), and levels had a positive correlation with individual proteinuria values (p < 0.05). Urinary IL-8/CXCL8 was significantly higher in relapsed SR than in SS patients in remission. No changes in MCP-1/CCL2 and RANTES/CCL5 levels were detected. Our findings suggest that IL-8/CXCL8 and TGF-beta1 are involved in the pathogenesis of INS: IL-8/CXCL8 associated with local changes in glomerular permeability and TGF-beta1 could be related to worse response to corticosteroids.

Differential chemokine expression in tubular cells in response to urinary proteins from patients with nephrotic syndrome.

BACKGROUND AND AIM: Comparison of urine proteins in idiopathic minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS) patients has been previously conducted, but the relationship between the severity of tubular injury and the composition of urine proteins in various kidney diseases is unknown. This study aimed to investigate the chemokine expression in human tubular cells in response to urine proteins from patients with nephrotic syndrome. METHODS: Urine proteins collected from patients with MCD or FSGS were extracted by ultrafiltration and coincubated with HK-2 cells. The expression of the RANTES and MIF genes and the activation of p38 and extracellular regulated kinase were determined. RESULTS: The urine proteins from both MCD and FSGS patients contained a primary band of proteins with Mr of approximately 62 kDa. The major cytokines present in urine proteins from MCD and FSGS patients were IL-6 and IL-8, while IL-1beta, IL-10, IL-12p70 and TNF-alpha were only detectable. We observed time- and dose-dependent increases in RANTES and MIF expression with urine protein treatment in HK-2 cells. The urine proteins from FSGS patients induced a higher expression of these two chemokines in HK-2 cells compared to the urine proteins from MCD patients. ERK and p38 were activated by urine proteins from either MCD or FSGS patients. Pretreatment with SB203580 or PD98059 abolished the increase in RANTES and MIF expression induced by urine proteins from FSGS patients, while only SB203580 suppressed the high expression induced by urine proteins from MCD patients. CONCLUSION: These findings indicate that the urine proteins from MCD and FSGS patients induce a differential expression of RANTES and MIF in tubular cells through distinct activation of MAPK-related signaling pathways.

[Urinary excretion of proinflammatory cytokines and transforming growth factor beta at early stages of diabetic nephropathy].

AIM: To examine correlations between urine excretion of proinflammatory cytokines, transforming growth factor beta (TGF-b) and changes in renal structure and function, quality of glycemia control in patients with type 1 diabetes mellitus. MATERIAL AND METHODS: Urinary excretion of interleukine 1-beta (IL-1b), monocytic chemoattractive protein-1 (MCP-1), RANTES and TGF-b was measured with enzyme immunoassay in 57 patients including 22 patients with normal albuminuria, 23--with microalbuminuria, 12--with macroalbuminuria. Creatinine clearance was subnormal in 8 patients with macroalbuminuria. The control group consisted of 10 healthy persons. Morphological examination of renal biopsies was performed in 8 patients with normoalbuminuria and 10 patients with microalbuminuria. RESULTS: Patients with normoalbuminuria had excretion of MCP-1 significantly higher than in controls. Microalbuminuria patients showed high excretion of IL-1b, MCP-1 and TGF-b. Excretion of IL-1b, MCP-1, RANTES and TGF-b in patients with macroalbuminuria was higher than in controls and other groups of patients. Excretion of cytokines and TGFb correlated inversely with glomerular filtration rate and hemoglobin level. Positive correlations were detected between excretion of IL-1b, MCP-1, TGFb and glycated hemoglobin A(1c). In patients with normo- and microalbuminuria cytokine and TGFb excretion correlated with thickness of glomerular and glomerular basal membrane. CD68-positive macrophages were detected in the intersticium of 1 patient with normoalbuminuria and 6 patients with microalbuminuria. CONCLUSION: Urinary excretion of proinflammatory cytokines and TGF-b was elevated in patients with DM-1 having micro- and macroalbuminuria suggesting participation of inflammation in development of diabetic nephropathy.

Urinary levels of RANTES and M-CSF are predictors of lupus nephritis flare.

OBJECTIVE: To explore a new predictor of renal flares after successful inductive treatment for diffuse proliferative glomerulonephritis(DPGN) in patients with lupus nephritis. METHODS: A cohort of patents with SLE DPGN who were treated initially with prednisone and cyclophosphamide were studied. Those who responded to inductive treatment were followed up for the occurrence of renal flares. Urinary levels of RANTES, MCP-1 and M-CSF were measured by ELISA. Other clinical and laboratory data were collected. The predictors and outcome of renal flare were analyzed. RESULTS: Seventy-three qualified patients with SLE DPGN were investigated. After a mean follow-up of 24.5 +/- 6.4 months, 22 patients experienced renal flares. The median time to relapse was 14.1 +/- 4.1 months. The patients experiencing renal flare showed higher urinary RANTES, MCP-1 and M-CSF. However, independent predictors of renal flares were increased urinary RANTES and M-CSF. Eight patents developed doubling of the serum creatinine (CRX2) level. The occurrence of renal flares was the only predictor of CRX2. CONCLUSIONS: Persistently increased urinary levels of RANTES and M-CSF after initial remission are predictors of renal flare in patients with SLE DPGN. Our results indicate monitoring urinary pro-inflammatory factors may direct us in managing those patients.

Mycophenolate mofetil treatment improves hypertension in patients with psoriasis and rheumatoid arthritis.

Evidence that was obtained in several experimental models and in strains of hypertensive rats indicates that infiltration of inflammatory cells and oxidative stress in the kidney play a role in the induction and maintenance of hypertension. Similar evidence is lacking in human hypertension, at least in part, because immunosuppressive treatment is unjustified in patients with hypertension. For addressing this issue, patients who were prescribed by their private physicians mycophenolate mofetil (MMF) for the treatment of psoriasis or rheumatoid arthritis and had, in addition, grade I essential hypertension and normal renal function were studied. Eight patients were studied before MMF was started, during MMF treatment, and 1 mo after MMF treatment had been discontinued. Other treatments and diet were unchanged in the three phases of the study. MMF therapy was associated with a significant reduction in systolic, diastolic, and mean BP. Urinary excretion of TNF-alpha was reduced progressively by MMF treatment and increased after MMF was discontinued. Reduction of urinary malondialdehyde, TNF-alpha, and RANTES excretion during MMF administration did not reach statistical significance but had a direct positive correlation with the BP levels. These data are consistent with the hypothesis that renal immune cell infiltration and oxidative stress play a role in human hypertension.

Messenger RNA expression of RANTES in the urinary sediment of patients with lupus nephritis.

BACKGROUND: Lupus nephritis is characterized by intra-renal inflammation. Patients with systemic lupus erythematosus (SLE) showed abnormal T-cell expression of RANTES (regulated upon activation, normal T cell expressed) and its level in their serum. The authors studied the mRNA expression of RANTES in the urinary sediment of lupus patients. METHODS: The authors studied 88 lupus patients, who were classified into active, remission and non-renal SLE groups according to the disease activity, 29 non-SLE and 10 healthy controls. Lupus activity was assessed by the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). Urinary mRNA expression of RANTES was studied by real-time quantitative polymerase chain reaction. RESULTS: The expression of RANTES in urinary sediment was significantly elevated in active group (P < 0.001). Expression level of RANTES correlated with the SLEDAI score (r = 0.57; P < 0.001) and renal score in SLEDAI (r = 0.60; P < 0.001). In addition, urinary expression of RANTES had significant correlation with degree of proteinuria, serum creatinine, albumin and estimated glomerular filtration rate. CONCLUSION: The authors conclude that the mRNA expression of RANTES was elevated in the urinary sediment of patients with active lupus nephritis. Measurement of urinary mRNA expression may be a novel non-invasive method for the assessment of lupus disease activity and the severity of renal involvement.

CC-chemokine RANTES is increased in serum and urine in the early post-transplantation period of human renal allograft recipients.

BACKGROUND: The chemokine RANTES is a potent chemoattractant for T cells and monocytes that has been shown to enhance inflammation. The aim of our study was to investigate whether RANTES is upregulated within the early post-transplantation period that may influence short-time allograft function rate. METHODS: Serum and urine samples from transplanted renal allograft recipients (n = 17) were obtained from specimens taken for diagnostic reasons. Four patients developed biopsy-proven rejection episodes within the first month. Time course of RANTES was studied within the first 12 days after renal transplantation using ELISA technique. Data were tested for significances between patients with rejection and without rejection, compared to healthy volunteers as controls, and correlated with clinical data. RESULTS: In the control group RANTES concentration was 37.2 +/- 2.7 ng/ml (serum) and 8.1 +/- 1.3 pg/ml (urine), respectively. In transplanted recipients serum RANTES was significantly upregulated up to 132 +/- 28 ng/ml on day 1 after transplantation and remained elevated within the first 12 days (n = 17). Time course of urine RANTES demonstrated elevated concentrations with 754 +/- 115 pg/ml on day 1 followed by an continuous decrease to 22.3 +/- 7 pg/ml on day 12 (n = 17). No significant differences could be detected between patients with rejection and without rejection episodes. CONCLUSIONS: In contrast to data of other urinary marker molecules (like IL-6), there are no significant differences between the rejection and non-rejection group. RANTES is therefore not suitable for early detection of rejection. Nevertheless, serum and urine RANTES concentrations were highly elevated in freshly transplanted renal allograft recipients reflecting an activated immune system.

[Serum level and urinary excretion of RANTES in patients with primary glomerulonephritis]. / Stezenie w surowicy oraz wydalanie z moczem RANTES u chorych z pierwotnymi glomerulopatiami.

Proteinuria plays a central role in the progression of glomerular disease, and there is growing evidence suggesting that it may determine tubular cell activation with release of proinflammatory chemokines and fibrogenic factors, leading to interstitial inflammatory reaction. Chemokines are proteins that contribute to the migration of leukocytes to sites of tissue injury. C-C chemokine receptor 5 is receptor for the C-C chemokine RANTES, which is expressed in inflammatory kidney diseases. To better understand the role of RANTES in various types of human glomerular diseases, we studied 53 patients with primary glomerular diseases (5 minimal change--MC; 4 focal glomerulosclerosis--FS; 4 membranous nephropathy--MN; 12--mesangial proliferative GN--MesPGN; 18 IgA nephropathy--IgAN; 6 membranoproliferative GN-MPGN, and 4 extracapillary GN-ExGN) and 10 healthy person. Renal biopsies were evaluated by light and immunofluorescence microscopy. RANTES concentrations in serum and urine were measured by ELISA (BIOSOURCE international kits). The treatment of patients consisted of 3 to 5 i.v. methylprednisolone pulses (1.0 g per single dose, average total 1.0 g/20 kg given alternate days) followed by oral prednisone 20 to 25 mg/day and six monthly i.v. cyclophosphamide 0.6 g/l m2/month. The study groups (except FS) showed a significantly higher concentration of RANTES in their sera compared with the control. The increase of urinary excretion for RANTES was 2-fold in patients with MN, and 8-fold in patients with ExGN but in patients with FS a significant decrease in urinary RANTES excretion was found. There was no significant differences in the urinary excretion of RANTES in other groups compared to a control group. In patient groups serum Cr showed significant correlations with interstitial volume in renal biopsy. No significant correlation was found between serum concentration of RANTES and their urinary excretion and other parameters considered (serum creatinine, urinary protein, serum protein concentration, and interstitial volume in renal biopsy). In patients with renal insufficiency (Cr > 1.3 mg%) and reduction of proteinuria > 50% after 1 year of treatment, the serum concentration and urinary secretion of RANTES was higher before treatment than in patients with protein reduction < 50%, and in patients with renal sufficiency. These results showed that patients with glomerular diseases who showed renal insufficiency and reduction of urinary protein after 1 year of immunosuppressive treatment revealed high levels of serum and urinary excretion of RANTES. It was thus suggested that the measurement of serum and urinary excretion of RANTES is useful in evaluating the degree of renal injury in patients with glomerular diseases after immunosuppressive treatment.