UNASSIGNED: Immunoglobulin A nephropathy (IgAN) has been reported to coexist with hepatitis B virus (HBV) infection. Despite the clinical significance of this association, there is a lack of comprehensive research investigating the impact of various common conditions following HBV infection and the potential influence of anti-HBV therapy on the progression of IgAN.
UNASSIGNED: We investigated 3 distinct states of HBV infection, including chronic HBV infection, resolved HBV infection, and the deposition of hepatitis B antigens in renal tissue, in a follow-up database of 1961 patients with IgAN. IgAN progression was defined as a loss of estimated glomerular filtration rate (eGFR) >40%. Multivariable cause-specific hazards models to analyze the relationship between HBV states and IgAN progression.
UNASSIGNED: Chronic HBV infection was identified as an independent risk factor for IgAN progression, supported by both prematching analysis (hazard ratio [HR], 1.61; 95% confidence interval [CI], 1.06-2.44; P = 0.024) and propensity-score matching analysis (HR, 1.74; 95% CI 1.28-2.37; P < 0.001). Conversely, resolved HBV infection showed no significant association with IgAN progression (HR, 1.01; 95% CI 0.67-1.52; P = 0.969). Moreover, the presence of HBV deposition in the kidneys and the utilization of anti-HBV therapy did not appear to be significant risk factors for renal outcomes (P > 0.05).
UNASSIGNED: Chronic HBV infection is an independent risk factor for IgAN progression, whereas resolved HBV infection is not. In patients with IgAN, management of concurrent chronic HBV infection should be enhanced. The presence of HBV deposition in the kidneys and the use of anti-HBV medications do not impact the kidney disease progression in patients with IgAN with concurrent HBV infection.

BACKGROUND: IgA vasculitis nephritis is the most common secondary IgA nephropathy. Urinary C4d have been identified associated with the development and progression in primary IgA nephropathy. However, its role in kidney disease progression of IgA vasculitis nephritis is still unclear.
METHODS: This study enrolled 139 patients with IgA vasculitis nephritis (IgAVN), 18 healthy subjects, 23 Focal segmental glomerulosclerosis patients and 38 IgA nephropathy (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% eGFR decline or ESKD, was assessed using Cox proportional hazards models and restricted cubic splines.
RESULTS: The levels of urinary C4d/creatinine in IgAVN and IgAN patients were higher than in healthy controls. Higher levels of urinary C4d/creatinine 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/creatinine). After adjustment for clinical data, higher levels of urinary C4d/creatinine were associated with kidney disease progression in IgA vasculitis nephritis (per ln transformed urinary C4d/creatinine, hazard ratio (HR) =1.573, 95% confidence interval (CI) 1.101-2.245; P = 0.013). Compared to the lower C4d/creatinine group, hazard ratio was 5.539(95%CI, 1.135-27.035; P = 0.034) for the higher levels group.
CONCLUSIONS: Higher levels of urinary C4d/creatinine were associated with kidney disease progression event in patients IgAVN.

Proteinuria is a surrogate end point for predicting long-term kidney outcomes in IgA nephropathy (IgAN) with levels<1g/day identified as a therapeutic target. However, this threshold has not been sufficiently studied. We quantified the associations of progression of IgAN with various levels of proteinuria.
Observational cohort study.
1,530 patients with IgAN and at least 12 months of follow-up at Peking University First Hospital.
Proteinuria levels updated over time (time-varying proteinuria, TVP).
A composite kidney outcome of a 50% reduction in the estimated glomerular filtration rate or end-stage kidney disease.
Marginal structural models.
After a median follow-up period of 43.5 (IQR, 27.2-72.8) months, 254 patients (16.6%) developed the composite kidney outcome. A graded association was observed between TVP and composite kidney outcomes with higher risk among those with proteinuria of≥0.5g/day. Compared with TVP<0.3g/day, the HRs for proteinuria levels of 0.3 to<0.5g/day, 0.5 to<1.0g/day, 1.0 to<2.0g/day, and≥2.0g/day were 2.22 (95% CI, 0.88-5.58), 4.04 (95% CI, 1.93-8.46), 8.46 (95% CI, 3.80-18.83), and 38.00 (95% CI, 17.62-81.95), respectively. The trend was more pronounced in patients with baseline proteinuria of≥1.0g/day, among whom a higher risk was observed with TVP of 0.3 to<0.5g/day compared with TVP<0.3g/day (HR, 3.26 [95% CI, 1.07-9.92], P=0.04). However, in patients with baseline proteinuria levels of<1g/day, the risk of composite kidney outcome only began to increase when TVP was≥1.0g/day (HR, 3.25 [95% CI, 1.06-9.90]).
Single-center observational study, selection bias, and unmeasured confounders.
This study showed that patients with IgAN and proteinuria levels of>0.5g/day, have an elevated risk of kidney failure especially among patients with proteinuria levels≥1.0g/day before initiating treatment. These data may serve to inform the selection of proteinuria targets in the treatment of IgAN.
The presence of proteinuria has often been considered a surrogate end point and a possible therapeutic target in clinical trials in IgA nephropathy (IgAN). Some guidelines recommend a reduction in proteinuria to<1g/day as a treatment goal based on the results of previous longitudinal studies. However, these findings may have been biased because they did not properly adjust for time-dependent confounders. Using marginal structural models to appropriately account for these confounding influences, we observed that patients with IgAN and proteinuria levels≥0.5g/day have an elevated risk of kidney failure, especially among patients who had proteinuria levels of≥1.0g/day before initiating treatment. These data may serve to inform the selection of proteinuria targets in the treatment of IgAN.

BACKGROUND: High serum phosphorus level has been reported to be a risk factor for disease progression in patients with chronic kidney disease, whereas, its role in IgA nephropathy (IgAN) still remains uncertain. This study aimed to investigate the association between serum phosphorus and progression of IgAN.
METHODS: A total of 247 patients diagnosed with IgAN from 2016.11 to 2019.12 at the First Affiliated Hospital of Xi\'an Jiaotong University were retrospectively enrolled in this study. The association between serum phosphorus and kidney disease progression events, defined as 30% estimated glomerular filtration rate (eGFR) decline or kidney failure, was evaluated using Cox models.
RESULTS: Serum phosphorus was an independent risk factor for poor renal outcome after adjusting for age, gender, urine protein, MAP, eGFR, hemoglobin, Oxford S and T scores (HR, 2.586; 95% CI, 1.238-5.400, p = 0.011). The addition of serum phosphorus to the reference model containing clinical and pathological variables significantly improved the risk prediction of IgAN progression (C statistic, 0.836; 95% CI, 0.783-0.889) as compared with the reference model (C statistic, 0.821; 95% CI, 0.756-0.886). The ability of serum phosphorus level to predict progression was much stronger in IgAN patients without use of immunosuppression (HR 5.173; 95% CI, 1.791-14.944; p = 0.002).
CONCLUSIONS: Higher serum phosphorus levels were independently associated with kidney disease progression in patients with IgAN, especially in those without immunosuppression. The addition of serum phosphorus to clinical and pathological data at the time of biopsy significantly improved risk prediction of IgAN progression.

UNASSIGNED: Coagulation disorders play a key role in chronic kidney disease, and the formation or elevation of plasma D-dimer levels reflects activation of the coagulation system. However, its relationship with the severity and progression of kidney disease in IgA nephropathy (IgAN) remains unclear.
UNASSIGNED: We assessed 1818 patients with IgAN diagnosed between 2002 and 2019 at the First Affiliated Hospital, Zhejiang University School of Medicine. Plasma D-dimer levels were measured at the time of the renal biopsy. The association between plasma D-dimer levels and kidney disease progression events, defined as a 50% decline in eGFR and end-stage kidney disease (ESKD), was tested using restricted cubic splines and Cox proportional hazard models.
UNASSIGNED: The median plasma D-dimer level was 220 (170-388.5) µg/L FEU, which was significantly higher than healthy controls 170 (170-202) µg/L FEU. Plasma D-dimer levels were positively correlated with proteinuria (r = 0.211, p < 0.001) and serum galactose-deficient IgA1 (r = 0.226, p = 0.004) and negatively correlated with eGFR (r=-0.127, p < 0.001) and Oxford T (p < 0.001) and C (p = 0.004) scores. After a median follow-up of 25.67 (13.03-47.44) months, 126 (6.93%) patients experienced composite kidney disease progression events. Higher plasma D-dimer levels were associated with an increased risk of kidney disease progression events (hazard ratio, 1.73; 95% confidence interval [95% CI], 1.40-2.23) per ln-transformed plasma D-dimer (p < 0.001), after adjustment for sex, age, proteinuria, Mean arterial pressure (MAP) and Oxford classification scores. In reference to the first tertile of plasma D-dimer, hazard ratios were 1.48 (95% CI, 0.76-2.88) for the second tertile, 3.03 (95% CI, 1.58-5.82) for the third tertile.
UNASSIGNED: High plasma D-dimer levels were associated with the progression of kidney disease severity in IgA nephropathy.

BACKGROUND: In chronic kidney disease, current guidelines recommend systolic blood pressure (SBP) below 120 mmHg. However, the renoprotective effect of intensive blood-pressure (BP) lowering on immunoglobulin A nephropathy (IgAN) remains undetermined. We aimed to determine the effect of intensive BP control on the progression of IgAN.
METHODS: At Peking University First Hospital, 1530 patients with IgAN were enrolled. An examination of the relationship between baseline and time-updated BP and composite kidney outcomes, defined as development of end-stage kidney disease (ESKD) or a 30% decline in estimated glomerular filtration rate (eGFR), was conducted. Baseline and time-updated BPs were modeled using multivariate causal hazards models and marginal structural models (MSMs).
RESULTS: In a median follow-up of 43.5 (interquartile range 27.2, 72.7) months, 367 (24.0%) patients experienced the composite kidney outcomes. No significant associations were found between baseline BP and the composite outcomes. Using MSMs with time-updated SBP for analysis, a U-shaped association was found. In reference to SBP 110-119 mmHg, hazard ratios (95% confidence intervals) for the SBP categories <110, 120-129, 130-139 and ≥140 mmHg were 1.48 (1.02-2.17), 1.13 (0.80-1.60), 2.21 (1.54-3.16) and 2.91 (1.94-4.35), respectively. The trend was more prominent in patients with proteinuria ≥1 g/day and eGFR ≥60 mL/min/1.73 m2. After analyzing time-updated diastolic BP, no similar trend was observed.
CONCLUSIONS: In patients with IgAN, intensive BP control during the treatment period may retard the kidney disease progression, but the potential risk of hypotension still needs to be considered.

This cross-sectional study aimed to investigate the association between plasma homocysteine (Hcy) and chronic kidney disease (CKD) in US patients with type 2 diabetes mellitus (T2DM).
We used data from the 2003-2006 National Health and Nutritional Examination Surveys (NHANES). CKD was defined as an estimated glomerular filtration rate < 60 ml/min/1.73 m2 and/or urinary albumin-creatine ratio ≥ 3 mg/mmol.
This study included 1018 patients with T2DM. The mean Hcy value was 10.2 ± 4.6 μmol/L. Among the patients, 417 (40.96%) had hyperhomocysteinemia (HHcy) and 480 (47.15%) had CKD. The Hcy level was higher in patients with CKD than in those without CKD. Compared to patients with normal Hcy, those with HHcy were older and had worse renal function. After full multivariate adjustment, HHcy was positively associated with the risk of CKD in US patients with T2DM (OR, 1.17; 95% CI, 1.11-1.22; P <  0.001), which for women was 1.15 (95% CI, 1.08 ~ 1.23; P <  0.001) and for men was 1.18 (95% CI, 1.1 ~ 1.27; P <  0.001).
HHcy was independently associated with CKD in patients with T2DM. Further prospective studies are warranted to investigate the effect of Hcy on CKD in patients with T2DM.

UNASSIGNED: The visit-to-visit variability (VVV) in blood pressure (BP) is an important risk factor for stroke and coronary heart disease and may also be associated with kidney damage and the development of chronic kidney disease (CKD). Data on the association between VVV in BP and the risk of CKD progression among patients with immunoglobulin A nephropathy (IgAN) are limited. We aimed to evaluate the relationships of VVV in BP with the progression of IgAN.
UNASSIGNED: We assessed 1376 patients with IgAN at Peking University First Hospital. The main VVV in BP was expressed as the standard deviation (SD), coefficient of variation (CV) and average real variability (ARV). The associations of variability in BP with composite kidney disease progression events, defined as a 50% decline in estimated glomerular filtration rate (eGFR) and kidney failure, were examined using Cox models.
UNASSIGNED: During a median follow-up of 44.1 months (interquartile range 23.0-76.7), 247 (18.0%) patients experienced composite kidney disease progression events. With a higher SD in systolic BP (SBP) values, the risk of kidney disease progression events increased {hazard ratio [HR] 1.07 [95% confidence interval (CI) 1.03-1.11]; P < .001} after maximal adjustment, including baseline SBP and mean SBP during the first 12-month period. Using the first quartile of SD SBP values as the reference, the risk of composite kidney disease progression events was higher among patients with higher SD SBP values; the HR was 2.12 (95% CI 1.31-3.44) in the highest quartile (P for trend < .001). A similar trend could be observed when analysing the SD of diastolic BP, but the risk was not significantly increased. The associations were similar when analysed with the CV and ARV.
UNASSIGNED: SBP variability was significantly associated with kidney disease progression in IgAN.

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.

UNASSIGNED: Proteinuria 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.
UNASSIGNED: We 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.
UNASSIGNED: In 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].
UNASSIGNED: In IgA nephropathy, ACR, PCR, and 24-h UP had a high correlation. ACR performed better in predicting the prognosis of IgA nephropathy.