Outcome Of IgA Nephropathy Research Articles

Treatment and outcome of IgA nephropathy in children from one single center experience

BackgroundThere is no standard recommendation for IgA nephropathy treatment in children.MethodsThis is a retrospective study. From 2012 to 2020, newly diagnosed primary IgAN followed up for at least 1 year were enrolled. The correlation of MESTC scores and clinical index including proteinuria, gross hematuria and renal dysfunction was analyzed. Treatment and clinical response of 6 month, 1year and 3 year at follow up were also analyzed. Complete renal remission was calculated with Kaplan-Meier analysis.ResultsThe median follow up was 36 months, from 12 months to 87months in 40 IgAN children. Angiotensin-converting enzyme inhibitor (ACEI) was applied to all patients. 30% received ACEI alone; 15% received glucocorticoids; 37.5% received glucocorticoids plus cyclophosphamide, 17.5% received glucocorticoids plus mycophenolate mofetil. Individuals with diffuse mesangial hypercellularity (M1) were more likely to have nephrotic range proteinuria compared to patients with M0 (80% vs. 20%, P < 0.01). Complete renal remission at 6-month, 1-year and 3-year follow up is 50.25%, 70% and 87.5% respectively. Five-year complete renal remission calculated by Kaplan-Meier analysis is 58.4%. Although without significant difference, there is trend of better survival with complete renal remission in group of nephrotic range proteinuria onset. There is no severe adverse effect.ConclusionThis study supports the use of glucocorticoids plus immunosuppressive in addition to ACEI in IgA nephrology pediatric patients with proteinuria. We suggest proactive immunosuppressive treatment in IgA nephropathy in children. This is from a single center in China as may not same results in other population.

Clinicopathological characteristics, risk factors and prognostic value of intrarenal vascular lesions in IgA nephropathy

BackgroundThe aim was to study clinicopathological characteristics, risk factors and renal outcome in IgA nephropathy (IgAN) patients with vascular lesions. MethodsWe enrolled a Chinese cohort with 458 biopsy-confirmed primary IgAN patients for a retrospective analysis. They were divided into three groups according to vascular lesions: no vascular lesions (n = 239), arterio-/arteriolosclerosis (n = 181) and microangiopathic lesions (n = 38). The clinicopathological features and renal outcome were recorded. In univariate and multivariate models, association between vascular lesions and renal outcome and vascular lesions associated clinical factors were analyzed. ResultsPatients with vascular lesions presented worse clinical characteristics with regard to blood pressure and kidney function, and segmental glomerulosclerosis (S1), tubular atrophy/interstitial fibrosis (T1/2) and lymphocytes and monocytes infiltration were more common. Furthermore, older age, hyperuricemia, proteinuria, global glomerulosclerosis and endocapillary hypercellularity (E1) were more severe in patients with simple arterio-/arteriolosclerosis. By multivariate logistic regression, age, MAP and eGFR were significantly associated with vascular lesions. Vascular lesions, especially arterio-/arteriolosclerosis, were significantly associated with poorer renal survival in IgAN patients, and renal survival was similar whether patients with arterio-/arteriolosclerosis received immunosuppressive therapy. In addition to eGFR, arterio-/arteriolosclerosis, along with arterial intimal fibrosis, was an independent predictor for renal survival in multivariate Cox analyses. ConclusionIgAN patients with vascular lesions, especially with arterio-/arteriolosclerosis, presented more severe clinicopathological features. Renal function, blood pressure and age contributed to distinguishing patients with vascular lesions. Arterio-/arteriolosclerosis lesions were associated with poorer renal survival.

Crescents proportions above 10% are associated with unfavorable kidney outcomes in IgA nephropathy patients with partial crescent formation

Purpose Whether different crescentic proportions determine the progression of IgA nephropathy (IgAN) with crescents in less than 50% of glomeruli remains controversial. We aimed to evaluate the relationship between different proportions of crescents and kidney outcomes in IgAN with partial crescent formation. Methods Patients diagnosed as IgAN, having at least two crescents and in less than 50% of glomeruli, were categorized into three groups: Group I (crescents in ≤10% of glomeruli), Group II (10%< crescents ≤25% of glomeruli) and Group III (crescents >25% of glomeruli). Baseline clinicopathological parameters were evaluated. The kidney endpoint was a composite of a ≥ 40% decline in the initial estimated glomerular filtration rate, end-stage kidney disease, and kidney disease-related death. Results Of 183 IgAN patients with crescents in less than 50% of glomeruli, baseline 24-hour urinary protein and immunosuppressive treatment varied among the three groups (p < 0.05). During a median follow-up of 57 months (interquartile range 28–86), 50 (27.3%) patients reached the composite outcome. Kaplan–Meier survival analysis revealed that kidney survival in Group II (p = 0.049) and Group III (p = 0.008) was significantly shorter than in Group I, with no significant difference between Group II and III (p = 0.2). After adjusting for clinical factors and MEST score based on the multivariate Cox regression analysis, a crescent proportion >10% (HR = 3.431, 95% CI 1.067–11.03, p = 0.039) was predictive of time to unfavorable kidney outcome, with model adjustments improving predictability (c-index: 0.817). Conclusion The proportion of crescents reaching 10% of glomeruli in IgAN was identified as an independent risk factor for kidney survival.

Immunosuppression versus Supportive Care on Kidney Outcomes in IgA Nephropathy in the Real-World Setting.

The efficacy of immunosuppression in the management of immunoglobulin A (IgA) nephropathy remains highly controversial. The study was conducted to assess the effect of immunosuppression, compared with supportive care, in the real-world setting of IgA nephropathy. A cohort of 3946 patients with IgA nephropathy, including 1973 new users of immunosuppressive agents and 1973 propensity score-matched recipients of supportive care, in a nationwide register data from January 2019 to May 2022 in China was analyzed. The primary outcome was a composite of 40% eGFR decrease of the baseline, kidney failure, and all-cause mortality. A Cox proportional hazard model was used to estimate the effects of immunosuppression on the composite outcomes and its components in the propensity score-matched cohort. Among 3946 individuals (mean [SD] age 36 [10] years, mean [SD] eGFR 85 [28] ml/min per 1.73 m 2 , and mean [SD] proteinuria 1.4 [1.7] g/24 hours), 396 primary composite outcome events were observed, of which 156 (8%) were in the immunosuppression group and 240 (12%) in the supportive care group. Compared with supportive care, immunosuppression treatment was associated with 40% lower risk of the primary outcome events (adjusted hazard ratio, 0.60; 95% confidence interval, 0.48 to 0.75). Comparable effect size was observed for glucocorticoid monotherapy and mycophenolate mofetil alone. In the prespecified subgroup analysis, the treatment effects of immunosuppression were consistent across ages, sexes, levels of proteinuria, and values of eGFR at baseline. Serious adverse events were more frequent in the immunosuppression group compared with the supportive care group. Immunosuppressive therapy, compared with supportive care, was associated with a 40% lower risk of clinically important kidney outcomes in patients with IgA nephropathy.

Long-Term Outcomes in IgA Nephropathy.

IgA nephropathy can progress to kidney failure, and risk assessment soon after diagnosis has advantages both for clinical management and the development of new therapeutics. We present relationships among proteinuria, eGFR slope, and lifetime risks for kidney failure. The IgA nephropathy cohort (2299 adults and 140 children) of the UK National Registry of Rare Kidney Diseases (RaDaR) was analyzed. Patients enrolled had a biopsy-proven diagnosis of IgA nephropathy plus proteinuria >0.5 g/d or eGFR <60 ml/min per 1.73 m 2 . Incident and prevalent populations and a population representative of a typical phase 3 clinical trial cohort were studied. Analyses of kidney survival were conducted using Kaplan-Meier and Cox regression. eGFR slope was estimated using linear mixed models with random intercept and slope. The median (Q1, Q3) follow-up was 5.9 (3.0, 10.5) years; 50% of patients reached kidney failure or died in the study period. The median (95% confidence interval [CI]) kidney survival was 11.4 (10.5 to 12.5) years; the mean age at kidney failure/death was 48 years, and most patients progressed to kidney failure within 10-15 years. On the basis of eGFR and age at diagnosis, almost all patients were at risk of progression to kidney failure within their expected lifetime unless a rate of eGFR loss ≤1 ml/min per 1.73 m 2 per year was maintained. Time-averaged proteinuria was significantly associated with worse kidney survival and more rapid eGFR loss in incident, prevalent, and clinical trial populations. Thirty percent of patients with time-averaged proteinuria of 0.44 to <0.88 g/g and approximately 20% of patients with time-averaged proteinuria <0.44 g/g developed kidney failure within 10 years. In the clinical trial population, each 10% decrease in time-averaged proteinuria from baseline was associated with a hazard ratio (95% CI) for kidney failure/death of 0.89 (0.87 to 0.92). Outcomes in this large IgA nephropathy cohort are generally poor with few patients expected to avoid kidney failure in their lifetime. Significantly, patients traditionally regarded as being low risk, with proteinuria <0.88 g/g (<100 mg/mmol), had high rates of kidney failure within 10 years.

301 The Association Between Surrogate Kidney Endpoints and Hard Clinical Outcomes in IgA Nephropathy: A Systematic Literature Review

301 The Association Between Surrogate Kidney Endpoints and Hard Clinical Outcomes in IgA Nephropathy: A Systematic Literature Review

Next-Generation Morphometry for pathomics-data mining in histopathology

Pathology diagnostics relies on the assessment of morphology by trained experts, which remains subjective and qualitative. Here we developed a framework for large-scale histomorphometry (FLASH) performing deep learning-based semantic segmentation and subsequent large-scale extraction of interpretable, quantitative, morphometric features in non-tumour kidney histology. We use two internal and three external, multi-centre cohorts to analyse over 1000 kidney biopsies and nephrectomies. By associating morphometric features with clinical parameters, we confirm previous concepts and reveal unexpected relations. We show that the extracted features are independent predictors of long-term clinical outcomes in IgA-nephropathy. We introduce single-structure morphometric analysis by applying techniques from single-cell transcriptomics, identifying distinct glomerular populations and morphometric phenotypes along a trajectory of disease progression. Our study provides a concept for Next-generation Morphometry (NGM), enabling comprehensive quantitative pathology data mining, i.e., pathomics.

Blood TGF-β1 and miRNA-21-5p levels predict renal fibrosis and outcome in IgA nephropathy.

IgA nephropathy(IgAN), the most common primary glomerulonephritis, often presents as advanced renal failure with end-stage renal disease at diagnosis. Tubulointerstitial injury and fibrosis on histology are the most important predictors of renal outcome. A non-invasive biomarker is required for assessment of progression in IgA nephropathy. We investigated the utility of blood profibrotic molecules, TGF-β1 and miRNA-21-5p(miR-21), to identify a non-invasive biomarker for renal fibrosis in IgAN. The study included 30 IgAN (mean age 31.5 ± 9years) at the time of initial diagnosis, 25 age-sex-matched healthy controls and 10 Lupus nephritis patients as disease controls. Serum TGF-β1 was analyzed by enzyme-linked immunosorbent assay and plasma miR-21 by qRT-PCR, normalized with U6-snRNA. The levels were correlated with clinical features, laboratory parameters, histological Oxford MEST-C score and renal outcome. The serum TGF-β1 and plasma miR-21 were significantly higher in patients with IgAN than in healthy controls. TGF-β1 significantly correlated with serum creatinine, eGFR, Oxford T score and miR-21. High plasma miR-21 was significantly associated with T score and interstitial inflammation. On multivariate analysis, high levels of TGF-β1 and miR-21 correlated with lower eGFR and T score, respectively. On a follow-up period of 21.5months, high miR-21 expression at diagnosis was associated (p = 0.02) with a poor renal outcome havinga shorter time to doubling of serum creatinine. High blood TGF-β1 and miR-21 expression at diagnosis of IgAN show significant correlation with renal function and degree of chronic tubulointerstitial injury on histology.

Comparison between outcomes of IgA nephropathy with nephrotic-range proteinuria and nephrotic syndrome: do podocytes play a role?

Background Nephrotic syndrome (NS) and nephrotic-range proteinuria (NRP) are uncommon in IgA nephropathy (IgAN), and their clinicopathology and prognosis have not been discussed. Podocytes may play an important role in both clinical phenotypes. Methods We investigated 119 biopsy-proven IgAN patients with proteinuria over 2 g/d. The patients were divided into three groups according to proteinuria level: the overt proteinuria (OP) group, NS group, and NRP group. In addition, according to the severity of foot process effacement (FPE), the patients were divided into three groups: the segmental FPE (SFPE) group, moderate FPE (MFPE) group, and diffuse FPE (DFPE) group. The outcome was survival from a combined event defined by a doubling of the baseline serum creatinine and a 50% reduction in eGFR or ESRD. Results Compared with the NRP group, patients in the NS group had more severe microscopic hematuria, presented with more severe endocapillary hypercellularity and had a higher percentage of DFPE. The Kaplan–Meier curve showed that MFPE patients had a better outcome in the NRP group <50% of tubular atrophy/interstitial fibrosis. In the multivariate model, the NRP group (HR = 17.098, 95% CI = 3.835–76.224) was associated with an increased risk of the combined event, while MFPE (HR = 0.260, 95% CI = 0.078–0.864; p = 0.028) was associated with a reduced risk of the combined event. After the addition of renin-angiotensin system inhibitors (RASi), the incidence of the combined event in the MFPE group (HR = 0.179, 95% CI = 0.047–0.689; p = 0.012) was further reduced. Conclusions NS presented more active lesions and more severe FPE in IgAN. NRP was an independent risk factor for progression to the renal endpoint, while MFPE indicated a better prognosis in NRP without obvious chronic renal lesions, which may benefit from RASi.

IgAN its clinical presentatio

Background: Clinical presentation, kidney biopsy findings and clinical outcomes of IgA nephropathy (IgAN) are highly variable. The objective of this study is to study the clinical presentation, histologic patterns and outcomes of IgAN in Pakistani population, as no significant data is available in international literature from this part of the world.&#x0D; Material and Methods: A retrospective chart review was conducted of all patients with biopsy proven IgAN between January 2007 and December 2017.

Prognostic Value of Triglyceride to High-Density Lipoprotein Cholesterol Ratio (TG/HDL-C) in IgA Nephropathy Patients.

BackgroundThe triglycerides to high-density lipoprotein cholesterol (TG/HDL-C) ratio is an easy-to-use atherogenic and prognostic marker which has attracted increasing attention these days. However, whether TG/HDL-C correlate with outcomes in IgA nephropathy (IgAN) patients remains unknown. To clarify these issues, we conducted this study.MethodsA total of 1146 patients from West China Hospital of Sichuan University were retrospectively analysed between 2008 and 2018.The demographic, clinical and pathological data of all patients at the time of biopsy were collected. Then, patients were divided into the high TG/HDL group (TG/HDL ≥ 1.495, N=382) and the low TG/HDL group (TG/HDL-C < 1.495, N=764) based on the optimal cut-off value of the TG/HDL-C using receive operating curve. Cox proportional hazard models and Kaplan–Meier curves were used to evaluate the renal outcomes of IgAN.ResultsThe median age of the patients was 33 (26-42) years, and 44.5% were men. By correlation analysis, we found that the TG/HDL-C ratio was negatively correlated with the eGFR (r = 0.250, P < 0.001) but positively correlated with proteinuria (r = 0.230, P< 0.001), BMI (r=0.380, P<0.001) and serum uric (r =0.308, P< 0.001). Patients with a higher TG/HDL-C ratio tended to have hypertension [odds ratio (OR), 1.987; 95% CI, 1.527-2.587; P<0.001] and more severe pathologic lesions with tubular atrophy/interstitial fibrosis (OR, 1.610; 95% CI, 1.203-2.154; P=0.001). During a median follow-up period of 54.1 (35.6-73.2) months, a high TG/HDL ratio was strongly associated with worse renal survival in IgAN patients (log-rank: P <0.001). Multivariate Cox analysis demonstrated that a high TG/HDL-C ratio (HR 1.775, 95% CI 1.056-2.798; P=0.029) was an independent predictive marker to ESRD.ConclusionIn this study, we addressed the importance of TG/HDL-C ratio as a predictive marker for IgAN progression.

The association of 5-year therapeutic responsiveness with long-term renal outcome in IgA nephropathy.

Immunoglobulin A nephropathy (IgAN) is the most common type of primary glomerulonephritis. Since most patients have a relatively benign renal prognosis, long-term follow-up is required. During such a long course of disease, relapse of IgAN is occasionally observed after upper respiratory tract infection or without any trigger. However, little is known about the impact of relapse on long-term renal outcomes. In this retrospective cohort study of biopsy-proven primary IgAN, we analyzed the association of 5-year therapeutic responsiveness (relapse) with the subsequent development of end-stage kidney disease (ESKD) using a 5-year landmark analysis (Cox model) and explored predictors of relapse from histological and clinical data at baseline. Among 563 patients from the exploratory cohort, most relapses (13.7%) occurred within 5years after treatment. Using 5-year landmark analysis, among 470 patients, 79 developed ESKD during a median follow-up period of 155months. Even after adjustment for clinicopathological relevant confounders, hazard ratios (95% confidence intervals) in the relapse and non-responder groups compared with the remission group were 2.86 (1.41-5.79) and 2.74 (1.48-5.11), respectively. Among 250 patients who achieved remission within 5years, proteinuria, eGFR, mesangial hypercellularity, endocapillary hypercellularity, segmental sclerosis, and crescent, but not interstitial fibrosis/tubular atrophy, were independent predictors of 5-year relapse in multivariable logistic regression analysis, CONCLUSIONS: Both relapsers and non-responders had similarly strong association with ESKD in patients with IgAN. We also confirmed the predictors of relapse 5years after renal biopsy, which may guide the treatment strategies for patients with IgAN who occasionally relapse after remission.

Clinicopathological characteristics, risk factors and renal outcome in IgA nephropathy with crescents.

The aim of the study was to investigate the clinicopathological characteristics, risk factors and renal outcome in IgA nephropathy (IgAN) patients with crescents. Four hundredand fifty-eight biopsy-proven primary IgAN patients included between January 2010 and October 2021 for a retrospective analysis were divided into three groups according to crescent score of the updated Oxford classification: C0 group (n = 255), C1 group (n = 187) and C2 group (n = 16). The clinicopathological features and renal outcomes were recorded. In univariate and multivariate models, the association between crescents and renal outcome and C2-associated clinical factors were analyzed. Patients with a higher proportion of crescents presented worse clinical characteristics with regard to kidney function, proteinuria, hematuria, hemoglobin, uric acid, cholesterol, and serum albumin, while global glomerulosclerosis, segmental adhesion, tuft necrosis, segmental glomerulosclerosis (S1), tubular atrophy/interstitial fibrosis (T1/2), and lymphocyte and monocyte infiltration were more severe. By multivariate logistic regression analysis, eGFR (OR 0.981, 95% CI 0.964-0.999, P = 0.039), proteinuria (OR 1.655, 95% CI 1.180-2.321, P = 0.004), and hematuria (OR 4.752, 95% CI 1.426-15.835, P = 0.011) were significantly associated with C2. C2 was significantly associated with poorer renal survival even in patients receiving immunosuppressive therapy. Nevertheless, only eGFR at baseline, rather than crescents, was anindependent predictor for renal survival in multivariate Cox analyses. IgAN patients with crescents presented more severe clinical and pathological features. Renal function, proteinuria and hematuria contributed to identifying patients with crescents. Crescents were associated with poorer renal survival, even in patients receiving immunosuppressive therapy, but it was not anindependent predictor.

The role of body mass index on IgA nephropathy prognosis: a systematic review and meta-analysis.

Recent studies show that obese patients have worse outcomes in IgA nephropathy as compared to normal weight patients. We performed a systematic review and meta-analysis of prospective, retrospective, randomized and nonrandomized studies, which studied the impact of obesity or high body mass index (BMI) on different parameters of IgA nephropathy prognosis and outcome. We searched through PubMed, Ovid/Medline, Web of Science, and the Cochrane Central Register of Controlled Trials (Wiley). We included 16 studies in our final analysis with a total of 4258 patients. Overall, there was a significantly lower estimated glomerular filtration rate (eGFR) in IgA nephropathy patients with BMI in the overweight/obese range than in those with normal BMI (mean difference 6.01, 95% CI 2.78-9.24ml/min/1.73 m2, P < 0.001), but no significant difference in serum creatinine or proteinuria levels. No studies measured GFR. There were contradictory results regarding the relationship between BMI and blood pressure, histological parameters or outcomes in patients with IgA nephropathy. Higher BMI in IgA nephropathy patients might be associated with lower kidney function, but this should be confirmed by measuring GFR. Evidence regarding other kidney damage parameters and outcomes is inconclusive.

Plasma Homocysteine as a Potential Marker of Early Renal Function Decline in IgA Nephropathy.

Hyperhomocysteinemia (HHcy) is very common among patients with chronic kidney disease (CKD), and related to the risk of cardiovascular events and mortality in these patients. However, the prevalence of HHcy in primary causes of CKD and its role in kidney disease progression are not well-understood. In this study, we investigated the prevalence of HHcy in different CKD stages in 221 patients with IgA nephropathy (IgAN) and 194 patients with other primary glomerular diseases. We also evaluated the association of homocysteine (Hcy) [after adjusted for estimated glomerular filtration rate (eGFR)] with CKD progression event, defined as ESKD or 50% decline in eGFR, in a cohort of 365 patients with IgAN. The prevalence of HHcy was 67.9% (150/221), 53.5% (76/142), 51.5% (17/33), and 42.1% (8/19) in patients with IgAN, membranous nephropathy, minimal change disease, focal segmental glomerulosclerosis, respectively. The Hcy/eGFR ratio was significantly associated with pathologic features of IgAN, including the proportion of global glomerulosclerosis (r = 0.38, p < 0.001), the proportion of ischemia originated glomerular sclerosis (r = 0.32, p < 0.001), and the severity of tubular atrophy/interstitial fibrosis (r = 0.57, p < 0.001). Importantly, Hcy/eGFR ratio was an independent risk factor for CKD progression event (hazard ratio, 1.38; 95% confidence interval, 1.13–1.68; p = 0.002). The risk of CKD progression events continuously increased with the Hcy/eGFR ratio, but reached a plateau when Hcy/eGFR ratio was >1.79. Our findings suggest that elevated Hcy/eGFR ratio may be an early marker of poor renal outcome in IgAN.

Comparison of 24-h Urine Protein, Urine Albumin-to-Creatinine Ratio, and Protein-to-Creatinine Ratio in IgA Nephropathy.

BackgroundProteinuria is a strong risk factor for renal outcomes in IgA nephropathy. Random urine protein-to-creatinine ratio (PCR), random albumin-to-creatinine ratio (ACR), and 24-h urine protein excretion (24-h UP) have been widely used in clinical practice. However, the measurement which is the best predictor of long-term renal outcomes remains controversial. This study aimed to compare the three measurements in IgA nephropathy.MethodsWe conducted a retrospective study of 766 patients with IgA nephropathy. The associations among baseline ACR, PCR, and 24-h UP with chronic kidney disease (CKD) progression event, defined as 50% estimated glomerular filtration rate (eGFR) decline or end stage kidney disease (ESKD), were tested and compared.ResultsIn this study, ACR, PCR, and 24-h UP showed high correlation (r = 0.671–0.847, P < 0.001). After a median follow-up of 29.88 (14.65–51.65) months, 51 (6.66%) patients reached the CKD progression event. In univariate analysis, ACR performed better in predicting the prognosis of IgA nephropathy, with a higher area under the receiver operating curve (ROC) curve than PCR and 24-h UP. After adjustment for traditional risk factors, ACR was most associated with composite CKD progression event [per log-transformed ACR, hazard ratio (HR): 2.82; 95% (95% CI): 1.31–6.08; P = 0.008].ConclusionsIn IgA nephropathy, ACR, PCR, and 24-h UP had a high correlation. ACR performed better in predicting the prognosis of IgA nephropathy.

POS-373 THE LEVEL OF URINARY C4d IN PATIENTS WITH IgA NEPHROPATHY IS ASSOCIATED WITH DISEASE PROGRESSION: A COHORT STUDY

Positive glomerular C4d staining, representative of lectin pathway activation, has been proven to be associated with unfavorable outcomes in IgA nephropathy (IgAN). Our previous study suggested that urinary C4d correlated positively with an increase in crescents. While the relationship between urinary C4d and disease severity and progression remains unelucidated. In this study, we enrolled 168 patients diagnosed of IgAN with varying proportions of crescents formation at the time of biopsy. An independent cohort of 107 IgAN patients were enrolled for validation. Kidney biopsy specimens were stained using immunohistochemistry. Urinay C4d levels at renal biopsy were measured by enzyme-linked immunosorbent assay. The primary endpoint was end-stage kidney disease (ESKD). Levels of urinary C4d/Urine creatine(C4d/Ucr) demonstrated the same tendency as the stepwise increase in glomerular C4d positivity (p for trend <0.001). Higher urinary C4d/Ucr levels were associated with a lower estimated glomerular filtration rate (eGFR); massive proteinuria; hypertension; and severe Oxford-M, Oxford-E, Oxford-T and Oxford-C scores. After a median follow-up of 19 months (interquartile range, 9–27 months), 53 (31.5%) participants reached end-stage of kidney disease (ESKD). High urinary C4d/creatinine ratio levels were independently and significantly associated with a risk of developing ESKD (hazard ratio [HR], per standard deviation increment of log transformed C4d/creatinine of 7.623; 95% confidence interval [CI]: 4.117–14.113). Urinary C4d/creatinine ratio was a potential useful biomarker that was associated with disease severity and progression in patients with IgAN and crescents.

The Density of Renal Lymphatics Correlates With Clinical Outcomes in IgA Nephropathy

IntroductionIgA nephropathy (IgAN) is the most common primary glomerulonephritis (GN) worldwide. The disease course fluctuates, and the most important challenge is the considerable variation in the time lag between diagnosis and the development of a hard clinical end point, such as end-stage kidney disease (ESKD). The reaction of renal tissue to damage resembles the common wound-healing response. One part of this repair in IgAN is the expansion of lymphatic vessels known as lymphangiogenesis. The aim of this work was to establish the prognostic value of the density of lymphatic vessels in the renal biopsy at the time of diagnosis, for predicting the risk of ESKD in a Spanish cohort of patients with IgAN.MethodsWe performed a retrospective multicenter study of 76 patients with IgAN. The end point of the study was progression to ESKD. The morphometric analysis of lymphatic vessels was performed on tissue sections stained with antipodoplanin antibody.ResultsDensity of lymphatic vessels was significantly higher in patients with IgAN with mesangial hypercellularity >50%, segmental sclerosis, higher degrees of interstitial fibrosis, and tubular atrophy. Patients with more lymphatic vessels had significantly higher values of proteinuria and lower estimated glomerular filtration rate (eGFR). A density of lymphatic vessels ≥8 per mm2 was associated with a significantly higher rate of progression to ESKD at 3 years from biopsy. After adjustment for the International IgAN prediction score, at the multivariate logistic regression, high density of lymphatic vessels (≥8 per mm2) remained significantly associated with a higher rate of early progression to ESKD.ConclusionThis study contributes to the understanding of the natural history of the progression to ESKD in patients with IgAN revealing the density of lymphatics vessels may optimize the prognostic value of the International IgA predicting tool to calculate the risk of ESKD, favoring the evaluation of new targeted therapies.

Correlation of E1 lesions and CD68 count with proteinuria and clinical outcome in IgA nephropathy

Background: IgA nephropathy (IgAN) has variable course; few patients have a benign presentation and other patients present with late stage disease. Endocapillary hypercellularity has a prognostic significance in IgAN. It is important to identify E1 lesions accurately. The use of CD68 immunohistochemistry marker to identify glomerular macrophages will standardize the reporting and help the clinicians prognosticate the patients. Subjects and Methods: The material is from a referral laboratory for renal biopsies in a tertiary care hospital. Renal biopsies are processed as per protocol including light microscopy, immunofluorescence and electron microscopy where ever required. CD68 was used in this study to identify macrophages in E1 lesions. A total of 1220 primary glomerular diseases were diagnosed from January 2019 till date. Out of these, IgA constituted 11.9% of primary glomerular diseases. Renal biopsies received were from the department of nephrology and various other nephrology centers. Biopsies were received in 10% buffered formalin. Immunofluorescence is done on all biopsies, and electron microscopy was done in few cases to differentiate from other lesions with dominant IgA deposits. CD68 was done in 50 cases of IgAN. Apart from hematoxylin and eosin stains, periodic acid-Schiff, Masson trichrome, Jones silver stain were also done. Results: IgAN constituted 11.9% of cases. Twenty-five cases of E0 and twenty-five cases of E1 lesions were correlated with clinical and morphological features. There was correlation with proteinuria and hypertension in E1 lesions. There was no significant correlation with the morphological variants like crescents, focal segmental glomerulosclerosis. Conclusions: Inter observer correlation of E lesions is poor in classifying IgAN. Use of CD68 is a useful adjunct to identify macrophages. E1 lesions have more proteinuria requiring treatment for delaying the progression to end stage disease. Despite significant association of E1 lesions with progression, there may be many unmeasured factors which would influence the outcome.

Prognostic Value of C4d Immunolabelling in Adult Patients With IgA Vasculitis.

Background and Objectives: Glomerular C4d deposits are associated the severity and outcomes of IgA nephropathy. Whether this holds true in immunoglobulin A vasculitis (IgAV) is not known. The main objective of the study was to analyze the prognostic value of glomerular C4d immunolabelling on kidney impairment in adults with IgAV.Design, Setting, Participants, Measurements: This retrospective cohort study included 120 adults with IgAV and a kidney biopsy performed between 1995 and 2018 in two French university hospital centers. All paraffin-embedded biopsies were reassessed according to Oxford classification. Immunofluorescence for C4d was performed in all cases. For analysis, patients were grouped according to positivity for C4d in the glomerular area. The main outcome was a composite endpoint of 50% increase in 24 h-proteinuria, or eGFR decrease by 50%, or kidney replacement therapy.Results: The median follow-up was 28.3 months. Twenty-three patients met the composite endpoint, 12 for kidney replacement therapy, 6 for an eGFR decrease >50% and 5 for a >50% increase in proteinuria. At time of biopsy, the median proteinuria was 1.9 g/24 h and the median eGFR 73.5 mL/min/1.73 m2. Among the 102 patients evaluable for C4d, 24 were positive on >30% glomeruli, mainly with a parieto-mesangial pattern. In this group, the initial proteinuria was more frequently nephrotic than in the C4d– group (60% vs. 33%, P = 0.039). Mesangial hypercellularity was more frequent in the C4d+ group (42% vs. 13%; P = 0.006) whereas macroscopic hematuria was more frequent in the C4d– group (18% vs. 0%; P = 0.03). After a median follow-up of 28 months, kidney survival did not differ according to C4d status.Conclusion: In a population of adult IgAV patients, glomerular positivity for C4d was associated with the severity of the kidney disease at presentation, but not with subsequent renal function deterioration.