Risk Factors for Development of ESRD in Patients with IgA Nephrology

IgA nephropathy (IgAN) accounts for 45.36% of primary glomerular disease in China; it is also a leading cause of end-stage renal disease (ESRD). Approximately 30% of patients with IgAN progressed to ESRD within 10 to 20 years; however, in some patients, disease progression was more rapid, with ESRD occurring within 10 years. Previous studies found associations between various clinical and pathological markers, including proteinuria, hypertension, decreased estimated glomerular filtration rate (eGFR) at time of biopsy, and MEST score (four histologic components: mesangial [M] and endocapillary hypercellularity [E], segmental sclerosis [S], and interstitial fibrosis/tubular atrophy [T]), and renal outcomes.

Compared with the studies that identified MEST score and clinical data at biopsy as factors for development of IgAN, there are few data on follow-up features. Researchers in China, led by Danhua Shu, MD, recently conducted an observational case-control study to examine the prognostic value of follow-up clinical data on the progression of IgAN, and to reexamine the predictive value of MEST score and clinical features at biopsy. Clinical follow-up data of interest were TA-P (time –average urinary protein), TA-UA (time-average uric acid), TA-Alb (time-average albumin), TA-Hb (time-average hemoglobin), and TA-TC (time-average total cholesterol). The researchers reported study results online in BMC Nephrology [2017. doi: 10.1186/s12882-016-0429-x].

The study involved 50 patients with ESRD with primary cause of IgAN and a short renal survival time of <10 years as the case group, and 100 IgAN patients with a renal survival time of >10 years after biopsy as the control group. Median renal survival time in the case group was 67 months. Distribution of initial chronic kidney disease (CKD) stage at time of renal biopsy was: CKD 1, 16%, n=8 cases; CKD 2, 24%, n=12 cases; CKD 3, 46%, n=23 cases; and CKD 4, 14%, n=7 cases. Median renal survival time in the control group was 132 months. Distribution of initial CKD stage at time of renal biopsy was: CKD 1, 55 cases, n=55; CKD 2, 35%; n=35 cases; CKD 3, 9%, n=9 cases; and CKD 4, 1%, n=1 case.

In the case group, the frequencies of M1, S1, T1, and T2 score were significantly higher than in the control group (P<.05). The case group also had higher levels of serum creatinine, UA, TC, 24-hour urinary protein, and the proportion of hypertension at biopsy compared with the control group (P<.05). Hemoglobin, Alb, eGFR and the proportion of hematuria history were lower in the control group than in the case group (P<.05).

The researchers calculated and compared average levels of each clinical feature of interest during follow-up. In the comparisons between cases and controls, there were differences in TA-P (2.5 vs 0.6 g/L; P<.001), TA-UA (7.8 vs 5.8 mg/dL; P<.001), TA-Hb (11.7 vs 13.3 g/dL; P<.001), TA-Alb (3.8 vs 4.3 g/dL; P<.001), and TA-TC (212.3 vs 194.7 mg/dL; P=.011).

Logistic regression was used to analyze clinical and pathological data to determine whether the data were associated with development of ESRD among the participants; TA-P was excluded due to its inaccurate property. In this study, TA-P was estimated from semi-quantified urine protein measurement, which may not have been able to reflect the accurate level of urine protein compared with albumin creatinine ratio or 24-hour urine protein measurement.

In univariate logistic analysis, there was an association between M1, S1, T1 or T2, high UA, TC, 24-hour urine protein levels, hypertension history at biopsy, and high TA-UA, TA-TC and increased risk for development of ESRD. There was an association between a decreased risk of ESRD and high levels of baseline eGFR, Hb, Alb, and TA-Hb and TA-Alb during follow-up and the presence of macro-hematuria. When analyzed with multivariate logistic regression, M1, eGFR at biopsy, TA-UA, and TA-Hb were independent risk factors for the development of ESRD among patients with IgAN.

Study limitations cited by the authors included the retrospective design and a selection bias.

In summary, the researchers said, “Patients with pathological assessment of M1, T1, or T2, impaired renal function, abnormal blood biochemical parameters and hypertension at biopsy should be paid more attention, and therapies aiming to keep UA and Hb levels under control and reduce urinary protein during the follow-up are highly recommended. Pathological type M may play an important role in IgAN outcomes among [the] Chinese population.”

Takeaway Points

  1. Chinese researchers conducted a single center, case-control study to examine the prognostic value of specified clinical data in predicting the development of end-stage renal disease (ESRD) in individuals with severe IgA nephropathy (IgAN).
  2. In comparisons of IgAN patients with renal survival time of <10 years after renal biopsy (case group) with patients with renal survival time of >10 years, differences in time-average (TA) uric acid, hemoglobin, albumin, total cholesterol, and urinary protein between the two groups were observed.
  3. IgAN patients with low baseline estimated glomerular filtration rate, low TA hemoglobin, and high TA uric acid were more likely to develop ESRD.