Renal Interstitial Inflammation Predicts Nephropathy Progression in IgA Nephropathy: A Two-Center Cohort Study.

INTRODUCTION: Renal interstitial inflammation often presents in immunoglobulin A nephropathy (IgAN), but its predictive role in kidney disease progression remains controversial. METHODS: This retrospective two-center cohort study included 1,420 adult IgAN patients between January 2003 and May 2018 followed for a median of approximately 7 years at two Chinese hospitals. The predictor was renal interstitial inflammation within the total cortical interstitium (none/mild [0-25%], moderate [26-50%], or severe [>50%]). For the further propensity score matching analyses, the participants with moderate and severe level of interstitial inflammation were pooled to match those with none/mild level of interstitial inflammation. The outcomes included the rate of kidney function decline, and the composite kidney endpoint event defined as a >40% reduction in the estimated glomerular filtration rate, end-stage kidney disease. Linear regression and Cox proportional hazards regression analyses were used to examine the association between interstitial inflammation and the outcomes. The predictive performance of the model also assessed using multivariate logistic regression analyses with the receiver operating characteristic curve analysis. Reclassification was assessed using the continuous net reclassification improvement and integrated discrimination improvement adapted for censoring for the assessment of the model with or without interstitial inflammation. RESULTS: For the check of reproducibility, the kappa statistic was 0.71, and intraclass correlation coefficient was 0.77. After adjustment for relating covariates, a higher level of interstitial inflammation was associated with a faster rate of kidney function decline (eGFR slope [mL/min/1.73 m2] of 1.34 [95% CI: -2.56 to 5.23], 3.50 [95% CI: -0.40 to 7.40], and 7.52 [95% CI: 3.02 to 12.01]) in the patients with none/mild, moderate, and severe interstitial inflammation, respectively, in the multivariable linear regression models and with an increased risk of kidney disease progression (HR for moderate vs. none/mild, 1.85; 95% CI: 1.10-3.13; HR for severe vs. none/mild, 2.95; 95% CI: 1.52-5.73) in the multivariable Cox proportional hazards models. Analyses in the propensity score-matched cohort, subgroups, and the sensitive analyses yielded consistent results. The receiver operating curves indicated a higher area under the curve of 0.83 in the model with interstitial inflammation compared with 0.81 in that without interstitial inflammation. In addition, incorporating interstitial inflammation into the International IgAN Risk Prediction Tool improved the diagnostic power of the algorithm to predict risk of progression. CONCLUSION: Interstitial inflammation is a reproducible pathologic parameter that may be adopted as a predictor for kidney disease progression in patients with IgAN.

The Association of Low Hemoglobin Levels with IgA Nephropathy Progression: A Two-Center Cohort Study of 1,828 Cases.

AIM: To investigate the relationship between hemoglobin levels and the progression of IgA nephropathy (IgAN). METHODS: In a two-center cohort of 1,828 cases with biopsy-proven IgAN, we examined the association of hemoglobin levels with the primary outcome of a composite of all-cause mortality or kidney failure defined as a 40% decline in eGFR, or ESKD (defined as eGFR <15 mL/min/1.73 m2 or need for kidney replacement therapy including hemodialysis, peritoneal dialysis, or kidney transplantation), or the outcome of kidney failure, assessed using Cox and logistic regression models, respectively, with adjustment for confounders. RESULTS: At baseline, mean age, eGFR, and hemoglobin levels were 33.75 ± 11.03 years, 99.70 ± 30.40 mL/min/1.73 m2, and 123.47 ± 18.36 g/L, respectively. During a median of approximately 7-year follow-up, 183 cases reached the composite outcome. After adjustment for demographic and IgAN-specific covariates and treatments, a lower quartile of hemoglobin was nonlinearly associated with an increased risk of the primary outcome or kidney failure in the Cox proportional hazards models (primary outcome: HR for quartile 3 vs. 4, 1.37; 95% CI, 0.83-2.25; HR for quartile 2 vs. 4, 1.18; 95% CI, 0.68-2.07; HR for quartile 1 vs. 4, 1.91; 95% CI, 1.15-3.17; kidney failure: HR for quartile 3 vs. 4, 1.39; 95% CI, 0.84-2.31; HR for quartile 2 vs. 4, 1.20; 95% CI, 0.68-2.11; HR for quartile 1 vs. 4, 1.83; 95% CI, 1.09-3.07) in the fully adjusted model. Then, hemoglobin levels were transformed to a binary variable for fitting the model according to the criteria for anemia of 110 g/L in the women and 120 g/L in men in China. The participants in the anemia group had an increased risk of developing outcomes compared with the nonanemia group in both genders (primary outcome: male: HR, 1.64; 95% CI, 1.01-2.68; female: HR, 1.68; 95% CI, 1.02-2.76; kidney failure: male: HR, 1.60; 95% CI, 0.97-2.64; female: HR, 1.58; 95% CI, 0.95-2.61) in the fully adjusted model. CONCLUSIONS: A low level of hemoglobin was nonlinearly associated with IgAN progression. The anemic IgAN patients presented a higher risk of developing poor outcomes compared with the nonanemic patients.

Uric Acid as a Predictor of Immunoglobulin A Nephropathy Progression: A Cohort Study of 1965 Cases.

BACKGROUND: The role of serum uric acid (SUA) level in the progression of Immunoglobulin A nephropathy (IgAN) remains controversial. METHODS: In a cohort of 1,965 cases with biopsy-proven IgAN, we examined the associations of SUA concentration with the primary outcome of a composite of all-cause mortality or kidney failure (defined as a reduction of estimated glomerular filtration rate [eGFR] by 40% from baseline, requirements for dialysis and transplantation), or the outcome of kidney failure alone, assessed using Cox and logistic regression models, respectively, with adjustment for confounders. RESULTS: At baseline, the mean age was 33.37 ± 11.07 years, eGFR was 101.30 ± 30.49 mL/min/1.73 m2, and mean uric acid level was 5.32 ± 1.76 mg/dL. During a median of 7-year follow-up, 317 cases reached the composite outcome of all-cause mortality (5 deaths) or kidney failure (36 cases of dialysis, 5 cases of renal transplantation, and 271 cases with reduction of eGFR by 40% from baseline). After adjustment for demographic and IgAN specific covariates and treatments, a higher quartile of uric acid was linearly associated with an increased risk of the primary outcome (highest versus lowest quartile, hazard ratio [HR] 2.39; 95% CI 1.52-3.75) and kidney failure (highest versus lowest quartile, HR 2.55; 95% CI 1.62-4.01) in the Cox proportional hazards regression models. In the continuous analysis, a 1 mg/dL greater uric acid level was associated with 16% increased risk of primary outcome (HR 1.16, 95% CI 1.07-1.25) and 17% increased risk of kidney failure (HR 1.17, 95% CI 1.08-1.27), respectively, in the fully adjusted model. The multivariate -logistic regression analyses for the sensitive analyses drew consistent results. In the subgroup analyses, significant interactions were detected that patients with mean arterial pressure (MAP) < 90 mm Hg or mesangial hypercellularity had a higher association of SUA with the incidence of the primary outcome than those with MAP ≥90 mm Hg or those without mesangial hypercellularity respectively. Hyperuricemia was not significantly associated with the risk of developing the primary outcome in elder patients (≥32 years old), patients with eGFR < 90 mL/min or with tubular atrophy/interstitial fibrosis. CONCLUSIONS: SUA level may be positively associated with the progression of IgAN. It was noticeable that the association of hyperuricemia with IgAN progression was less significant in patients with elder age, lower eGFR, or tubular atrophy/interstitial fibrosis, which may be due to some more confounders in association with the IgA progression in these patients. Future prospective studies are warranted to confirm these findings and to investigate the underlying mechanisms.

[Long-term Effect of the Treatment of IgA Nephropathy by Tonifying Shen, Activating Blood Stasis, Dispelling Wind-Dampness Combined with Western Medicine].

Objective To observe the long-term effect of tonifying Shen, activating blood stasis, dispelling wind-dampness (TSABSDWD) combined with Western drugs (WD) for IgA nephropathy. Methods A single center retrospective case-control study was used. The clinical and laboratory examinations, pa- thology of renal biopsy, and treatment programs of IgA nephropathy were obtained from primary IgA ne- phropathy patients (confirmed from renal biopsy at authors' hospital) from Jan 1st, 2008 to Dec 31 , 2008. Patients were assigned to Group A (basic treatment +Chinese herbs) and Group B (basic treatment +Chi- nese herbs + glucocorticoid and/or immune inhibitors). A follow-up visit started from the confirmation of re- nal biopsy to Dec 31, 2008, for at least 12 months. The end point event was defined as entering end stage renal disease (ESRD), estimated glomerular filtration rate (eGFR) decreased by more than 50%, or SCr was doubled. The differences in clinical manifestations, lab indicators and etc. were compared between be- fore treatment and after 1 year of treatment/till the end of follow-ups. The accumulative kidney survival rate was calculated using Kaplan-Meier method. The curve for accumulative kidney survival rate was drawn. Re- sults A total of 219 cases were included, 49 in Group A and 170 in Group B. In Group A, there were 7 pa- tients (14.0%) with Shen deficiency syndrome, 21 cases (43.0%) with Shen deficiency blood stasis syn- drome, 8 (16. 0%) with Shen deficiency wind-dampness syndrome, 13 cases (27. 0%) with Shen deficien- cy blood stasis wind-dampness syndrome. In Group B there were 12 patients (7.1%) with Shen deficiency syndrome, 47 cases (27. 6%) with Shen deficiency blood stasis syndrome, 22 (12.9%) with Shen defi- ciency wind-dampness syndrome, 89 cases (52.4%) with Shen deficiency blood stasis wind-dampness syndrome. No statistical difference in age, sex, or follow-up period between the two groups (P >0.05). Compared with Group A, the disease courser was shorter, 24 h urination increased more, levels of SCr and blood urea nitrogen (BUN) increased higher, plasma albumin decreased lower in Group B (P <0. 05). Compared with before treatment, 24 h urination and counts of urinary red blood cells (RBCs) decreased more in the two groups after 1-year treatment, and decreased further till the end of follow-up (P <0. 05). The total effective rate was 89. 0% (1951219). The total effective rate of Group A was 89. 8% (44/49), with no patient entry into endpoint event. The total effective rate of Group B was 88. 8%(151/170). Totally 5 pa- tients arrived at endpoint event in Group B, 4 in ESRD, 1 with eGFR decreased by more than 50%, or SCr doubled. Compared with Group B, the complete relief rate was higher in Group A (P <0. 01). The accumulative kidney survival rate was 100. 0%, 100. 0%, 98. 0% and 96. 1% in the 219 patients at year 1 , 3, 5, 7, re- spectively using Kaplan-Meier method. Conclusions Programs based on theory of Shen disease wind- dampness in CM and in integrative medicine could be used in treating IgA nephropathy according to differ- ent conditions. Long-term observation showed this program could significantly improve patients' conditions. The 7-year accumulative kidney survival rate was 96. 1%.