Background The Oxford Classification of the pathology of immunoglobulin A (IgA) nephropathy, developed in 2009, is highly predictive of renal prognosis. It has been validated in different ...populations, but the results remain inconsistent. Study Design Systematic review and meta-analysis. Setting & Population Patients with biopsy-proven primary IgA nephropathy. Selection Criteria for Studies Studies assessing the Oxford Classification of IgA nephropathy published between January 2009 and December 2012 were included following systematic searching of the MEDLINE and EMBASE databases. Predictor 4 pathologic lesions of the Oxford Classification: mesangial hypercellularity (M), endocapillary hypercellularity (E), segmental glomerulosclerosis (S), and tubular atrophy/interstitial fibrosis (T). Outcome Kidney failure defined as doubled serum creatinine level, 50% decline in estimated glomerular filtration rate, or end-stage kidney disease. Results 16 retrospective cohort studies with 3,893 patients and 570 kidney failure events were included. In a multivariate model, HRs for kidney failure were 0.6 (95% CI, 0.5-0.8; P < 0.001), 1.8 (95% CI, 1.4-2.4; P < 0.001), and 3.2 (95% CI, 1.8-5.6; P < 0.001) for scores of M0 (mesangial hypercellularity score ≤0.5), S1 (presence of segmental glomerulosclerosis), and T1/2 (>25% tubular atrophy/interstitial fibrosis), respectively, without evidence of heterogeneity. Pooled results showed that E lesions were not associated with kidney failure (HR, 1.4; 95% CI, 0.9-2.0; P = 0.1), with evidence of heterogeneity ( I2 = 54.1%; P = 0.01). Crescent (C) lesions were associated with kidney failure (HR, 2.3; 95% CI, 1.6-3.4; P < 0.001), with no evidence of heterogeneity ( I2 = 14.7%; P = 0.3). Limitations All studies were retrospective. This was not an individual-patient-data meta-analysis. Conclusions This study suggests that M, S, T, and C lesions, but not E lesions, are associated strongly with progression to kidney failure and thus should be included in the Oxford Classification system.
Background The outcomes of pregnancy in immunoglobulin A nephropathy (IgAN) are controversial. This cohort study assessed the effects of pregnancy on kidney disease progression and risk factors for ...adverse pregnancy outcomes in patients with IgAN. Study Design A cohort study. Setting & Participants Women of child-bearing age with IgAN and minimum follow-up of 1 year after biopsy from December 2003 to September 2014. Predictors Pregnancy, treated as a time-dependent variable; baseline (at time of biopsy) estimated glomerular filtration rate (eGFR), proteinuria, blood pressure, and kidney pathology (Oxford MEST classification). Outcomes Kidney disease progression event, defined as 30% decline in eGFR or end-stage kidney disease; rate of eGFR decline; and adverse pregnancy outcomes, including severe preeclampsia and fetal loss. Results Of 413 patients enrolled, 266 (64.4%), 101 (24.5%), 40 (9.6%), and 6 (1.5%) had chronic kidney disease (CKD) stages 1, 2, 3, and 4, respectively. During follow-up, 104 had 116 pregnancies, of which 110 continued beyond week 20; 309 patients did not become pregnant. After adjustment for age, eGFR, mean arterial pressure, proteinuria, and pathology class at the time of biopsy, subsequent pregnancy among patients with CKD stages 3 to 4, but not CKD stages 1 to 2, was associated with faster eGFR decline (−7.44 vs −3.90 mL/min/1.73 m2 per year; P = 0.007) and increased incidence of kidney progression events (HR, 5.14; 95% CI, 1.16-22.74) compared with patients who did not become pregnant. Limitations Relatively small sample size and single-center experience. Conclusions Pregnancy accelerated kidney disease progression in women with IgAN and CKD stage 3, but not in those at stage 1 or 2.
Background The outcomes of pregnancy in immunoglobulin A nephropathy (IgAN) are uncertain. This study assessed the effects of pregnancy on kidney disease progression and risk factors for adverse ...pregnancy outcomes in IgAN. Study Design A matched-cohort study. Setting & Participants Women with IgAN with at least one pregnancy, 1 year of follow-up, and kidney function and proteinuria measurement at baseline (time of biopsy) matched with nonpregnant women with IgAN from Peking University First Hospital. Predictors Pregnancy, treated as a time-dependent variable; proteinuria; hypertension; and estimated glomerular filtration rate (eGFR). Outcomes Kidney disease progression, defined as eGFR halving or end-stage kidney disease; rate of eGFR decline; and adverse pregnancy outcomes, including severe pre-eclampsia, intrauterine death, embryo damage, fetal malformation, and induced and spontaneous abortions. Results Of 239 female patients, 62 women had 69 pregnancies and 62 matched nonpregnant patients were selected as controls. Pregnant patients had median proteinuria at baseline with protein excretion of 1.27 (range, 0.06-7.25) g/d and mean eGFR of 102.3 (range, 40.0-139.0) mL/min/1.73 m2 . During a mean follow-up of 45.7 months, 4 patients in the pregnancy group and 6 in the nonpregnancy group had kidney disease progression events. Time-dependent Cox analysis showed that pregnancy was not an independent risk factor for kidney disease progression events (HR, 1.2; 95% CI, 0.3-5.7). There was no significant difference in the median rate of eGFR decline in the 2 groups (−2.5 vs −2.4 mL/min/1.73 m2 per year; P = 0.7). Adverse pregnancy outcomes were observed in 15 patients. Proteinuria during pregnancy (OR, 1.39; 95% CI, 0.96-2.01) was a borderline predictor of adverse pregnancy outcomes. Limitations Retrospective study, most patients had preserved kidney function, study underpowered to detect a difference in kidney failure events. Conclusions The study does not permit a definitive conclusion about the effect of pregnancy on kidney disease progression in IgAN.
