Long-term follow-up of IgA nephropathy: clinicopathological features and predictors of outcomes.

Background: The establishment of the Oxford classification and newly developed prediction models have improved the prognostic information for immunoglobulin A nephropathy (IgAN). Considering new treatment options, optimizing prognostic information and improving existing prediction models are favorable. Methods: We used random forest survival analysis to select possible predictors of end-stage kidney disease among 37 candidate variables in a cohort of 232 patients with biopsy-proven IgAN retrieved from the Norwegian Kidney Biopsy Registry. The predictive value of variables with relative importance >5% was assessed using concordance statistics and the Akaike information criterion. Pearson's correlation coefficient was used to identify correlations between the selected variables. Results: The median follow-up period was 13.7 years. An isolated analysis of histological variables identified six variables with relative importance >5%: T %, segmental glomerular sclerosis without characteristics associated with other subtypes (not otherwise specified, NOS), normal glomeruli, global sclerotic glomeruli, segmental adherence and perihilar glomerular sclerosis. When histopathological and clinical variables were combined, estimated glomerular filtration rate (eGFR), proteinuria and serum albumin were added to the list. T % showed a better prognostic value than tubular atrophy/interstitial fibrosis (T) lesions with C-indices at 0.74 and 0.67 and was highly correlated with eGFR. Analysis of the subtypes of segmental glomerulosclerosis (S) lesions revealed that NOS and perihilar glomerular sclerosis were associated with adverse outcomes. Conclusions: Reporting T lesions as a continuous variable, normal glomeruli and subtypes of S lesions could provide clinicians with additional prognostic information and contribute to the improved performance of the Oxford classification and prognostic tools.

Validation of two IgA nephropathy risk-prediction tools using a cohort with a long follow-up.

BACKGROUND: Recently, two immunoglobulin A (IgA) nephropathy-prediction tools were developed that combine clinical and histopathologic parameters. The International IgAN Prediction Tool predicts the risk for 50% declines in the estimated glomerular filtration rate or end-stage kidney disease up to 80 months after diagnosis. The IgA Nephropathy Clinical Decision Support System uses artificial neural networks to estimate the risk for end-stage kidney disease. We aimed to externally validate both prediction tools using a Norwegian cohort with a long-term follow-up. METHODS: We included 306 patients with biopsy-proven primary IgA nephropathy in this study. Histopathologic samples were retrieved from the Norwegian Kidney Biopsy Registry and reclassified according to the Oxford Classification. We used discrimination and calibration as principles for externally validating the prognostic models. RESULTS: The median patient follow-up was 17.1 years. A cumulative, dynamic, time-dependent receiver operating characteristic analysis showed area under the curve values ranging from 0.90 at 5 years to 0.83 at 20 years for the International IgAN Prediction Tool, while time-naive analysis showed an area under the curve value at 0.83 for the IgA Nephropathy Clinical Decision Support System. The International IgAN Prediction Tool was well calibrated, while the IgA Nephropathy Clinical Decision Support System tends to underestimate risk for patients at higher risk and overestimates risk in the lower risk categories. CONCLUSIONS: We have externally validated two prediction tools for IgA nephropathy. The International IgAN Prediction Tool performed well, while the IgA Nephropathy Clinical Decision Support System has some limitations.

Utilizing the MEST score for prognostic staging in IgA nephropathy.

BACKGROUND: The Oxford classification/MEST score is an established histopathologic scoring system for patients with IgA nephropathy (IgAN). The objective of this study was to derive a prognostic model for IgAN based on the MEST score and histopathologic features. METHODS: A total of 306 patients with biopsy-proven primary IgAN were included. Histopathologic samples were retrieved from the Norwegian Kidney Biopsy Registry and reclassified according to the Oxford classification. The study endpoint was end-stage renal disease (ESRD). Patients were subclassified into three risk models based on histologic features (Model A), a composite score calculated from the adjusted hazard ratio values (Model B), and on quartiles (Model C). RESULTS: The mean follow-up time was 16.5 years (range 0.2-28.1). In total, 61 (20%) patients reached ESRD during the study period. Univariate analysis of M, E, S, T and C lesions demonstrated that all types were associated with an increased risk of ESRD; however, a multivariate analysis revealed that only S, T and C lesions were associated with poor outcomes. Statistical analysis of 15-year data demonstrated that Models A and B were as predictive as the MEST score, with an area-under-the-curve at 0.85. The Harrel c index values were 0.81 and 0.80 for the MEST score and Models A and B, respectively. In the present cohort, adding C lesions to the MEST score did not improve the models prognostic value. CONCLUSIONS: Patients can be divided into risk classes based on their MEST scores. Histopathologic data provide valuable prognostic information at the time of diagnosis. Model B was the most suitable for clinical practice because it was the most user-friendly.

Anxiety and Depression in Patients with Intracranial Arachnoid Cysts-A Prospective Study.

BACKGROUND: Arachnoid cysts yield cognitive deficits that are normalized after surgical cyst decompression. OBJECTIVE: The present study aimed to investigate whether arachnoid cysts also affect symptoms of anxiety and depression, and if surgical cyst decompression leads to reduction of these symptoms. METHODS: Twenty-two adult patients (13 men and 9 women) with symptomatic temporal or frontal cysts were included in this questionnaire (Hospital Anxiety and Depression Scale [HADS])-based prospective study. The mean time between answering the preoperative questionnaire and surgery was 37 days. The patients answered the same HADS questionnaire 3-6 months postoperatively. RESULTS: Preoperatively, both patients with frontal (N = 4) and patients with temporal (N = 18) cyst had higher mean HADS anxiety scores than those found in the general population. For patients with temporal cyst, there was a significant or near-significant difference in anxiety and depression scores and the combined scores between those with right-sided cysts and those with left-sided cysts. Postoperatively, the HADS scores normalized and were no longer different from those of the general population. The difference in scores between patients with right and left temporal cyst also disappeared. CONCLUSIONS: Patients with arachnoid cyst have higher levels of anxiety and depression than do the general population and these scores were normalized after decompressive cyst surgery. We further found a hemispheric asymmetry: patients with a right temporal cyst showed higher anxiety, depression, and combined scores than did patients with a left temporal cyst. Also, this disparity normalized after cyst decompression. Thus, arachnoid cysts seem to affect not only cognition but also the level of affective symptoms.