Predictive prognostic value of glomerular C3 deposition in IgA nephropathy.

BACKGROUND: IgAN is the most common primary glomerulonephritis worldwide. However, the pathogenesis of IgAN remains unknown. Currently, there is evidence that C3 deposition plays a role in disease development. This study aimed to investigate clinical, pathological features, and prognosis of adult IgAN patients with C3 deposition, as well as explore the role of complement activation in disease progression. METHODS: A total of 821 patients with biopsy-proven IgAN were included in this study. Patients were divided into three different groups according to their C3 deposition intensity. Clinical and pathological characteristics were compared between groups. Logistic analysis was used to estimate the relationship between C3 deposition and the Oxford scoring system. Univariate and multivariate Cox proportional hazard regression models were used to analyze the effect of the presence of C3 deposits on the prognosis of patients with IgA nephropathy. Kaplan-Meier survival analysis was used to evaluate the cumulative incidence of renal progression between groups. RESULTS: Patients with C3 deposition exhibited more severe clinical and pathological features and had a higher score according to the Oxford scoring system. With the increasing intensity of C3 deposition, patients present more hematuria, crescents, heavier interstitial inflammatory cell infiltration and a higher score on segmental sclerosis lesions. Logistic regression identified a positive relationship between C3 deposition and histopathology. Univariate and multivariate Cox regression indicated that C3 deposition was an independent risk factor for IgAN severity. The Kaplan-Meier survival curves indicated that patients with positive C3 deposition had a worse prognosis compared to those without C3 deposition. CONCLUSIONS: Patients with positive glomerular C3 deposition presented with more severe clinical and histopathological characteristics and a higher score on the Oxford scoring system. With the increasing intensity of C3 deposition, IgAN patients were more likely to present with high level of microscopic hematuria, fibrous crescents, interstitial inflammatory cell infiltration, and a higher score on segmental sclerosis lesions. C3 deposition at the time of renal biopsy is likely an independent risk factor for IgA nephropathy severity and progression.

IgA nephropathy with acute kidney disease: Characteristics, prognosis, and causes.

BACKGROUND: The clinical manifestations and prognosis of IgA nephropathy (IgAN) are diverse. Some patients may present with kidney dysfunction lasting shorter than 3 months and meet the acute kidney disease (AKD) criteria. This study aimed to investigate the clinicopathological features, causes and prognosis of newly diagnosed cases of IgAN with AKD. METHODS: 1320 IgAN patients diagnosed via kidney biopsy between January 2012 and June 2018 were included in this retrospective study, with a median follow-up period of 35 months. We analyzed the clinicopathological, etiological variables, as well as short-term and long-term prognosis. The main outcome was a composite event of 40% decline in eGFR, kidney failure or death. RESULTS: Incidence of AKD was 8.8% in the newly diagnosed IgAN patients, and was found to be an independent risk factor affecting the short-term (HR, 7.1; 95% CI, 2.3-22.2; P = 0.001) and long-term (HR, 1.8; 95% CI, 1.2-2.6; P = 0.006) prognosis, respectively. The most common cause of AKD was malignant hypertension-related AKD (MHT-AKD; 24.1%), followed by hematuria-related AKD (H-AKD; 12.9%), nephrotoxic-drug-exposure-related AKD (NTDE-AKD; 12.1%) and crescents-related AKD (C-AKD; 11.2%). The patients in AKD group had more severe clinicopathological characteristics and poor short-term and long-term prognosis than non-AKD group. In subgroup analysis, the MHT-AKD had the worst 5 years survival rate, followed by NTDE-AKD and C-AKD, whereas H-AKD had the best survival rate. CONCLUSIONS: AKD is not rare among IgAN patients, and is an independent risk factor for short-term and long-term prognosis. IgAN patients with AKD resulting from different causes have different prognosis.

Normotensive and hypertensive Immunoglobulin a nephropathy with ischemic renal injury: clinicopathological characteristics and prognosis.

OBJECTIVES: This study aimed to investigate the clinicopathological characteristics and prognosis of normotensive and hypertensive IgAN patients with ischemic renal injury. METHODS: A total of 344 cases of IgAN with ischemic renal injury were included in the study, including 99 normotensive IgAN patients (28.8%) and 245 hypertensive IgAN patients (71.2%). In addition, 467 IgAN patients without ischemic renal injury were included as controls, including 205 normotensive patients and 262 hypertensive patients. Clinicopathological and prognostic data were collected and analyzed. RESULTS: Compared with patients without ischemic renal injury, IgAN patients with ischemic renal injury displayed a higher proportion of hypertention, a higher proportion of ischemic glomerulosclerosis, tubular atrophy/interstitial fibrosis and vascular lesions (all p < .05). There was no significant difference in cumulative survival between the normotensive IgAN patients groups (Log-rank χ2 = 0.479; p = .489). Furthermore, ischemic renal injury was not a risk factor for end-point events in normotensive IgAN patients (HR = 1.103; 95% CI: 0.279-4.365; p = .889). There was lower cumulative survival in hypertensive IgAN patients with ischemic renal injury (Log-rank χ2 = 11.352, p = .001). Moreover, ischemic renal injury was a risk factor for end-point events in hypertensive IgAN patients (HR = 1.889; 95% CI: 1.124-3.178; p = .016). CONCLUSIONS: Ischemic renal injury can occur in normotensive IgAN patients. Although the pathological changes may not affect the long-term prognosis of normotensive IgAN patients, the prognosis for hypertensive IgAN patients remains poor. Therefore, increased attention should be paid to the clinical management of ischemic lesions in hypertensive IgAN patients.

Overlapping obesity-related glomerulopathy and immunoglobulin A nephropathy: clinical and pathologic characteristics and prognosis.

BACKGROUND: In this study, we investigated the clinical and pathologic characteristics and prognosis of overlapping obesity-related glomerulopathy (ORG) and immunoglobulin A nephropathy (IgAN) (ORG + IgAN), which is rare in the clinic. METHODS: We included 62 cases of ORG + IgAN, 110 cases of ORG without other glomerulopathy (ORG alone) and 124 cases of IgAN without other glomerulopathy (IgAN alone). The clinical, pathologic and prognostic data were collected and compared. RESULTS: ORG + IgAN patients showed a higher incidence of body mass index (BMI), higher incidence of hyperuricemia, higher incidence of hypertriglyceridemia and higher blood glucose than the IgAN alone(all P < 0.05). ORG + IgAN patients presented with higher incidence of microscopic hematuria, greater mesangial cell proliferation and a higher proportion of crescents than the ORG alone (all P < 0.05). The ORG + IgAN patients who received corticosteroid or immunosuppressive therapy achieved a higher cumulative rate of partial or complete remission (PR or CR, P = 0.009). However, there was no significant difference in the cumulative renal survival rate between the ORG + IgAN patients in the glucocorticoids/immunosuppressors and non-glucocorticoids/immunosuppressors groups (P = 0.356). Obesity-related focal segmental glomerulosclerosis (O-FSGS) and body mass index (BMI) were significantly associated with poor prognosis (all P < 0.05). CONCLUSIONS: ORG + IgAN should be considered in obese patients who present with metabolic abnormalities and microscopic hematuria. Although corticosteroid or immunosuppressive therapy achieves higher cumulative incidence rates of PR or CR, there is no benefit to long-term prognosis but an increased risk of infection. Moreover, O-FSGS and BMI are significantly associated with poor prognosis.

External Validation of the International IgA Nephropathy Prediction Tool.

BACKGROUND AND OBJECTIVES: The International IgA Nephropathy Network recently developed and externally validated two models to predict the risk of progression of IgA nephropathy: full models without and with race. This study sought to externally validate the International IgA Nephropathy Prediction Tool in a large, independent, and contemporary cohort in China. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We included 1373 patients with biopsy-confirmed primary IgA nephropathy from The First Affiliated Hospital of Zhengzhou University from January 2012 to May 2018 and calculated predicted risks for each patient. The outcomes of interest were a 50% decline in eGFR or kidney failure. We assessed the performance of both models using discrimination (concordance statistics and Kaplan-Meier curves between subgroups), calibration (calibration plots), reclassification (net reclassification improvement and integrated discrimination improvement), and clinical utility (decision curve analysis). RESULTS: The median follow-up was 29 months (interquartile range, 21-43 months; range, 1-95 months), and 186 (14%) patients reached the kidney outcomes of interest. Both models showed excellent discrimination (concordance statistics >0.85 and well separated survival curves). Overall, the full model without race generally underestimated the risk of primary outcome, whereas the full model with race was well calibrated for predicting 5-year risk. Compared with the full model without race, the full model with race had significant improvement in reclassification, as assessed by the net reclassification improvement (0.49; 95% confidence interval, 0.41 to 0.59) and integrated discrimination improvement (0.06; 95% confidence interval, 0.04 to 0.08). Decision curve analysis showed that both full models had a higher net benefit than default strategies, and the model with race performed better. CONCLUSIONS: In this study, both full models demonstrated remarkable discrimination, acceptable calibration, and satisfactory clinical utility. The relatively short follow-up time may have limited the validation of these models.