Search

Background: Immunoglobulin A (IgA) vasculitis nephritis (IgAVN) is the most common secondary IgA nephropathy (IgAN). Urinary C4d have been identified associated with the development and progression in primary IgAN; however, its role in kidney disease progression of IgAVN is still unclear., Methods: This study enrolled 139 patients with IgAVN, 18 healthy subjects, 23 focal segmental glomerulosclerosis patients and 38 IgAN patients. Urinary C4d levels at kidney biopsy were measured using enzyme-linked immunosorbent assay. The association between urinary C4d/creatinine and kidney disease progression event, defined as 40% estimated glomerular filtration rate decline or end-stage kidney disease, was assessed using Cox proportional hazards models and restricted cubic splines., Results: The levels of urinary C4d/creatinine (Cr) in IgAVN and IgAN patients were higher than in healthy controls. Higher levels of urinary C4d/Cr were associated with higher proteinuria and severe Oxford C lesions, and glomerular C4d deposition. After a median follow-up of 52.79 months, 18 (12.95%) participants reached composite kidney disease progression event. The risk of kidney disease progression event was higher with higher levels of Ln(urinary C4d/Cr). After adjustment for clinical data, higher levels of urinary C4d/Cr were associated with kidney disease progression in IgAVN [per Ln-transformed urinary C4d/Cr, hazard ratio 1.573, 95% confidence interval (CI) 1.101-2.245; P = .013]. Compared with the lower C4d/Cr group, the hazard ratio was 5.539 (95% CI 1.135-27.035; P = .034) for the higher levels group., Conclusions: Higher levels of urinary C4d/Cr were associated with kidney disease progression event in patients with IgAVN., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)

Background: C4d mesangial deposition, a hallmark of lectin pathway activation in immunoglobulin A nephropathy (IgAN), has been shown to be associated with risk of kidney failure. To date, the relationship between urinary C4d and renal outcome remain unelucidated., Methods: A total of 508 patients with biopsy-proven IgAN were enrolled in this study, whose baseline urine samples at the time of biopsy were collected and the levels of urinary C4d were quantified by enzyme-linked immunosorbent assay. The time-averaged C4d (TA-C4d) and the change in proteinuria were measured in sequential urine samples obtained from IgAN patients. The kidney progression event was defined as a 50% estimated glomerular filtration rate (eGFR) decline or end-stage kidney disease or death., Results: After a median follow-up of 36 months, 70 (13.8%) of the participants reached the kidney progression event. Higher levels of urinary C4d/Ucr were found to be associated with decreased eGFR, massive proteinuria, lower serum albumin levels, hypertension, and severe Oxford E and T scores. Upon adjusting for traditional risk factors (including demographics, eGFR, proteinuria, hypertension, Oxford pathologic score and immunosuppressive therapy), elevated levels of urinary C4d/Ucr were independently associated with an increased risk of chronic kidney disease progression [adjusted hazard ratio (HR) per standard deviation increment of log-transformed C4d/Ucr: 1.46; 95% CI 1.04-2.06; P = .030]. In reference to the low C4d group, the risk of poor renal outcome increased for the high C4d group (adjusted HR 1.93; 95% CI 1.05-3.54; P = .033). Additionally, a low baseline C4d level was independently associated with a favorable proteinuria response to immunosuppressive therapy at 3 months (adjusted relative risk 2.20; 95% CI 1.04-4.63, P = .038)., Conclusion: The urinary C4d, serving as a non-invasive biomarker, is associated with the progression of IgAN and holds the potential to predict proteinuria response in this disease., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)

C4d urinary excretion varies according to the risk of graft rejection or progression of chronic allograft nephropathy. The most common maintenance immunosuppression (IS) schemes include cyclosporine (CSA) or tacrolimus (TAC) with azathiopryne (AZA) or mycophenolate mophetil (MMF). The chosen IS may influence kidney transplant outcomes and possibly modify urinary C4d. The aim of the study was to determine whether early C4d urinary excretion varies in patients after kidney allograft transplantation (KTx) regarding administered IS and if these factors may help to predict long-term KTx outcomes. The study involved 185 patients who underwent KTx. The urinary specimens were assessed by enzyme-linked immunosorbent assay test for C4d excretion. To increase the objectivity, C4d excretion was divided by urinary creatinine excretion (ng/mgCr). The study population was grouped according to the IS scheme, that is, CSA + AZA, CSA + MMF, and TAC + MMF. At baseline, the greatest C4d urinary excretion was noticed in patients treated with CSA + AZA, 199.5 ± 175.9 ng/mL (5.3 ± 7.1 ng/mgCr) and the lowest in those in whom tacrolimus and mycophenolate mophetil was administered, 166.6 ± 186.3 ng/mL (3.9 ± 6.2 ng/mgCr). In the CSA + MMF group, C4d excretion was 195.6 ± 200.3 ng/mL (5.0 ± 6.6 ng/mgCr). Statistically significant differences were seen only between the CSA + AZA and TAC + MMF groups, analysis of variance P < 0.05 (P < 0.01 for C4d/urinary creatinine ratio). No statistically significant differences were found in graft survival rates between different immunosuppressive regimens. Although early C4d measurements vary in patients after kidney allograft transplantation regarding administered IS, this IS dependant variation does not seem to affect the long-term graft survival.

Unlabelled: The C4d urinary excretion seems to increase with the risk of graft rejection or progression of chronic allograft nephropathy although its impact on long-term kidney transplant (KTx) outcomes remains unclear. Presently the most common maintenance immunosuppression schemes (IS) includes corticosteroids and cyclosporine or tacrolimus (Tac) with mycophenolane mophetil (MMF), and Tac combined with MMF is regarded to be superior to other schemes. The aim of the study was to determine whether the initial (1-3 months post KTx) level of C4d urinary excretion may help to predict long-term kidney allograft transplantation outcomes in patients treated with Tac+MMF as maintenance IS., Material and Methods: The study involved 66 patients who had undergone kidney allograft transplantation. The urine specimens taken from the morning urine portion was assessed by ELISA test for C4d excretion. To increase the objectivity of the assessment all measurements were divided by urinary creatinine excretion (ng/mgCr). The study population was grouped according the calculated Roc curve (the cut off value of the urinary C4d excretion 13.1 ng/mgCr; AUC 0.93; 95% CI 0.74-0.95) into LC4d and HC4d, C4d below or above 13.1 ng/mgCr., Results: The mean C4d urinary excretion was 166.6 +/- 186.3 ng/mL (3.9 +/- 6.2 ng/mgCr), in LC4d and HC4d 34.8 +/- 102.2 ng/mL (1.1 +/- 6.4 ng/mgCr) and 347.3 +/- 255.7ng/mL (19.2 +/- 5.9 ng/mgCr), respectively. In accord with the division of study population, the statistically significant differences were seen between LC4d and HC4d in urinary C4d excretion Z = 4.4; p = 0.019 (Z = 4.9, p = 0.011 for excretion calculated per urinary creatinine). Kaplan-Meier curve analysis demonstrated a higher graft survival rate in LC4d than in HC4d group (p = 0.048 by log-rank) in ten years follow-up., Conclusions: In patients treated with tacrolimus and mycophenolate mophetil as a maintenance immunosuppression, the lower C4d urinary excretion in the early post-transplant period seems to be a low significance prognostic marker of a better long-term kidney allograft transplantation outcome.

Introduction: The C4d deposits as well as its urinary excretion are markers of the humoral acute kidney graft rejection. The pre-transplant dialysis modality influences on the post-transplant outcomes and it is possible that it may modify C4d urinary excretion., Aim: The aim of the study was the assessment of the pre-transplant dialysis modality on late C4d urinary excretion., Material and Methods: The study comprised 185 patients who underwent kidney allograft transplantation (KTx). The urinary specimens taken from the morning urine portion was assessed by ELISA test for C4d excretion. To increase the objectivity of the assessment all measurements were divided by urinary creatinine excretion. The study population was grouped according the pre-transplant dialysis modality i.e. hemo- and peritoneal dialysis, Results: In the study the C4d urinary excretion in patients treated with hemodialysis was higher than in peritoneal dialysis, irrespectively whether in direct measurements 221.1 ± 239.9 ng/ml vs 156.4 ± 188.7 ng/ml (p < 0.05) or when calculated per urinary creatinine 5.2 ± 7.1 ng/mgCr i 3.4 ± 7.9 ng/mgr (p < 0.05)., Conclusions: Pre-transplant dialysis modality influences late C4d urinary excretion.

Introduction: Recent data describes the involvement of compliment elements in humoral kidney graft rejection. The C4d deposits in peritubular capilars are the marker of compliment activity and the element of humoral acute graft rejection. The aim of the study was the assessment of C4d urinary excretion in early and late post-kidney transplant periods., Material and Methods: The study comprised 185 patients who underwent kidney allograft transplantation (KTx). The urinary specimens taken from the morning urine portion was assessed by ELISA test for C4d excretion. To increase the objectivity of the assessment all measurements were divided by urinary creatinine excretion. The study population was grouped according the post-transplant time i.e. <1 and >1 year after KTx., Results: In the study the C4d urinary excretion in patients <1 year and >1 year post kidney transplantation were 4.6 ± 7.5 and 5.3 ± 7.9 ng/mgCr, respectively. The mean C4d excretion was 4.8 ± 7.6 ng/mgCr. The values did not differ significantly. The direct assessment of C4d excretion (not divided per creatinuria) were also comparable in the study groups (207.2 ± 261.8 ng/ml and 212.9 ± 249.3 ng/ml, respectively)., Conclusions: C4d urinary excretion did not depend on post-transplant time.

Introduction: The C4d urinary excretion varies according to the risk of graft rejection or progression of chronic allograft nephropathy. The most common maintenance immunosuppression (IS) schemes includes cyclosporine (CSA) ortacrolimus (TAC with azathiopryne (AZA) or mycophenolane mophetil (MMF). The chosen IS may influence on the kidney transplant outcomes and possibly modify C4d urinary secretion. The aim of the study was to assess whether IS scheme may influence on C4d urinary excretion., Material and Methods: The study involved 185 patients who underwent kidney allograft transplantation (KTx).The urinary specimens taken from the morning urine portion was assessed by ELISA test for C4d excretion. To increase the objectivity of the assessment all measurements were divided by urinary creatinine excretion (ng/mg Ucr). The study population was grouped according the IS scheme, i.e., CSA+AZA, CSA+MMF and TAC+MMF., Results: The highest C4d urinary excretion was noticed in patients treated with CSA+AZA--210 +/- 229 ng/ml (5.1 +/- 7.9 ng/mg Ucr) and the lowest in those in whom tacrolimus and mycophenolane mophetil was administered -198?188 ng/ml (4.4 +/- 7.1 ng/mg Ucr). In CSA+MMF group C4d excretion was 207?256 ng/ml (4.7 +/- 7.7 ng/mg Ucr). The statistically significant differences were seen only between CSA+AZA and TAC+MMF groups--ANOVA p<0.05 (p<0.01 for excretion calculated per Ucr)., Conclusions: C4d urinary excretion in kidney graft recipients depends on immunosuppression scheme and is the lowest in patients treated with tacrolimus and mycophenolane mophetil.

This study aimed to develop urine protein fingerprint models for the diagnosis of acute rejection (AR) and complement split product positive (C4d+) acute humoral rejection (AHR) following renal allograft transplantation. Urine samples from 101 renal transplant recipients were analysed by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry combined with bioinformatics. The patients comprised 36 with stable allograft function (stable group), 10 with acute tubular necrosis (ATN) and 55 with AR (20 with C4d- acute cellular rejection [ACR] and 15 with C4d+ AHR). The ATN group was differentiated from the stable group with a sensitivity and specificity of 100% (pattern 1). The stable group was differentiated from the AR group with a specificity of 86.4% and a sensitivity of 85.4% (pattern 2). The C4d- ACR subgroup was differentiated from the C4d+ AHR subgroup with a specificity and sensitivity of 95% and 80%, respectively (pattern 3). It is concluded that urine protein fingerprint analysis can provide a non-invasive tool to diagnose AR and C4d+ AHR.

Background: C4d-staining in peritubular capillaries (PTC) in allograft biopsies is a hallmark of antibody-mediated rejection (AMR). This study investigated whether urinary C4d correlates with C4d-staining in PTC, allowing for a noninvasive screening procedure., Methods: Urine samples from 34 patients with diffuse C4d-staining in PTC (C4d-pos group) and 68 urine samples from patients with negative C4d-staining in PTC (C4d-negative group) matched 1:2 according to proteinuria and time posttransplant were compared regarding urinary C4d-levels., Results: Overall, urinary C4d/creatinine-ratios (C4d/C) were not different between the C4d-positive and the C4d-negative group (P=0.55). Urinary C4d/C strongly correlated with total protein/creatinine-ratios (P/C) (r2=0.53; P<0.0001) and albumin/creatinine-ratios (r2=0.52; P<0.0001). C4d/C were not different between C4d-pos and C4d-negative patients with P/C>50 mg/mmol (P=0.57) and P/C<50 mg/mmol (P=0.65), respectively. However, in both the C4d-positive and the C4d-negative group urinary C4d/C were significantly higher in patients with P/C>50 mg/mmol than in patients with P/C<50 mg/mmol (P