Predicting Progression of IgA Nephropathy: New Clinical Progression Risk Score

IgA nephropathy (IgAN) is a common cause of end-stage renal disease (ESRD) in Asia. In this study, based on a large cohort of Chinese patients with IgAN, we aim to identify independent predictive factors associated with disease progression to ESRD. We collected retrospective clinical data and renal outcomes on 619 biopsy-diagnosed IgAN patients with a mean follow-up time of 41.3 months. In total, 67 individuals reached the study endpoint defined by occurrence of ESRD necessitating renal replacement therapy. In the fully adjusted Cox proportional hazards model, there were four baseline variables with a significant independent effect on the risk of ESRD. These included: eGFR [HR = 0.96(0.95–0.97)], serum albumin [HR = 0.47(0.32–0.68)], hemoglobin [HR = 0.79(0.72–0.88)], and SBP [HR = 1.02(1.00–1.03)]. Based on these observations, we developed a 4-variable equation of a clinical risk score for disease progression. Our risk score explained nearly 22% of the total variance in the primary outcome. Survival ROC curves revealed that the risk score provided improved prediction of ESRD at 24th, 60th and 120th month of follow-up compared to the three previously proposed risk scores. In summary, our data indicate that IgAN patients with higher systolic blood pressure, lower eGFR, hemoglobin, and albumin levels at baseline are at a greatest risk of progression to ESRD. The new progression risk score calculated based on these four baseline variables offers a simple clinical tool for risk stratification

H-1 NMR spectroscopy analysis of metabolites in the kidneys provides new insight into pathophysiological mechanisms: applications for treatment with Cordyceps sinensis

National Nature Science foundation of China [30270613, 30771000]; Foundation of Science and Technology Commission of Shanghai Municipality [08dz1900502, 07JC14037]The number of patients with chronic kidney disease (CKD) is continuously growing worldwide. Treatment with traditional Chinese medicine might slow the progression of CKD. In this study, we evaluated the renal protective effects of the Chinese herb Cordyceps sinensis in rats with 5/6 nephrectomy. Male Sprague-Dawley mice (weighing 150-200 g) were subjected to 5/6 nephrectomy. The rats were divided into three groups: (i) untreated nephrectomized group (OP group, n = 16), (ii) oral administration of C. sinensis-treated (4 mg/kg/day) nephrectomized group (CS group, n = 16) and (iii) sham-operated group (SO group, n = 16). The rats were sacrificed at 4 and 8 weeks after 5/6 nephrectomy, and the kidneys, serum and urine were collected for H-1 nuclear magnetic resonance spectral analysis. Multivariate statistical techniques and statistical metabolic correlation comparison analysis were performed to identify metabolic changes in aqueous kidney extracts between these groups. Significant differences between these groups were discovered in the metabolic profiles of the biofluids and kidney extracts. Pathways including the citrate cycle, branched-chain amino acid metabolism and the metabolites that regulate permeate pressure were disturbed in the OP group compared to the SO group; in addition, these pathways were reversed by C. sinensis treatment. Biochemistry and electron microscopic images verified that C. sinensis has curative effects on chronic renal failure. These results were confirmed by metabonomics results. Our study demonstrates that C. sinensis has potential curative effects on CKD, and our metabonomics results provided new insight into the mechanism of treatment of this traditional Chinese medicine

Survival and Survival ROC curves for the Risk Score. (a)

<p>Kaplan-Meier outcome-free survival curves by risk score tertiles; <b>(b)</b> the Risk Score’s ROC curves for predicting ESRD at 24 months, 60 months and 120 months.</p

Kaplan-Meier Outcome-free Survival Curves.

<p><b>(a)</b> low (red) versus high (black) baseline eGFR group; <b>(b)</b> patients with a baseline diagnosis of anemia (red) versus no anemia (black); <b>(c)</b> patients with hypoalbuminemia (red) versus normoalbuminemia (black); <b>(d)</b> patients with systolic hypertension (red) versus normotensives (black). Censor points are denoted by vertical tick lines.</p

Performance of the Published ESRD Prediction Scores.

<p>The ROC curves for predicting renal outcomes within (a) 24 months, (b) 60 months, and (c) 120 months of follow-up. The Risk Score from this study (black) is contrasted against the Goto et al. score (blue), RENAAL score (red) and the Berthoux et al. score (green); (d) comparisons of AUCs (and their 95% CIs) and R² for the four risk score prediction models.</p

Multivariate Cox Regression with Stepwise Selection (n = 619).

<p>SBP: systolic blood pressure.</p>*<p>Renal outcome defined as end-stage renal disease (ESRD).</p>**<p>Renal outcome defined as 50% decline from baseline eGFR.</p><p># The risk score was calculated from the coefficients of independent risk factors in model 1.</p

Univariate analysis of baseline variables with renal end points for ESRD.

<p>SBP: systolic blood pressure;</p><p>DBP: diastolic blood pressure;</p><p>MAP: mean arterial pressure;</p><p>UA: uric acid;</p><p>WBC: white blood cell count.</p><p># p<0.05.</p

Detailed Analysis of Hemoglobin and Serum Albumin Levels. (a)

<p>the distributions of hemoglobin levels for IgAN patients and healthy controls; <b>(b)</b> hemoglobin levels by the degree of renal impairment; <b>(c)</b> serum albumin distributions in IgAN patients and healthy controls; <b>(d)</b> serum albumin levels by the degree of renal impairment; <b>(e)</b> correlation between serum albumin and urine protein excretion by three different groups of proteinuria. Significance code: * p<0.05, ** p<0.01, *** p<0.001.</p