Validation of the Oxford classification of IgA nephropathy: valid or invalid?
Authors: Christian D. Peters, Troels Ring
Journal: Kidney International (2015)

To the Editor: Coppo et al.1.Coppo R. Troyanov S. Bellur S. et al.Validation of the Oxford classification of IgA nephropathy in cohorts with different presentations and treatments.Kidney Int. 2014; 86: 828-836Abstract Full Text Full Text PDF PubMed Scopus (297) Google Scholar assess the validity of the Oxford classification of IgA nephropathy by evaluating what they call the predictive value of renal pathology variables on the rate of renal function decline and renal survival. What they appear to be doing, however, is reporting the ability of the said variables to ‘explain’ the observed outcomes in the samples generating the model. When the authors state that they validated the multivariate models from the original Oxford classification study, does that mean that the identified models were used on patients not generating the models? The variability in a predictive model is likely to be greater than in an explanatory model and the form different,2.Shmueli G. To explain or to predict?.Stat Sci. 2010; 25: 289-310Crossref Scopus (1542) Google Scholar was that the case? Trying to understand what has then in fact been ‘explained’ is not easy. In Table 4 is presented the results of ‘prediction’ of rapid progression versus observed rapid progression. For those not on immunosuppression therapy and using both clinical and pathological variables, a positive predictive value (PPV) of 0.77 and a negative predictive value (NPV) of 0.65 can be calculated compared with 0.63 for both PPV and NPV for those on immunosuppression. This is not impressive, especially as it uses the same data twice: in generating and assessing the model. The authors conclude that immunosuppression abolishes the ‘predictive’ effect of addition of pathological variables to clinical variables. This is interesting to know but less so than whether the treatment in fact helped the patients. Was that possible to tell? The rate of renal function decline was obtained by fitting straight line, which could lead to problems if in fact treatment was effective. ‘Obvious outliers were censored’—were they only few and evenly distributed? When the authors state that an early renal biopsy may be an advantage as these patients with well-preserved glomerular filtration rate on renin-angiotensin system blockade and with little proteinuria have a destiny, which is not determined by advanced renal damage as it is absent, the overall perspective of the study seems questionable. How could in the real world an early biopsy by itself result in a better prognosis? The predictive value of the mesangial hypercellularity (M), endocapillary proliferation (E), segmental glomerulosclerosis (S), and tubular atrophy/interstitial fibrosis (T) (MEST) criteria relies on accurate histological classification, and pathology is by far no exact science. Thus, as noted by one of the authors in a recent paper concerning the Oxford Classification of IgAN in a European cohort study: ‘…agreement between local and review pathologists in the scoring of lesions was good for tubular atrophy/interstitial fibrosis and segmental sclerosis, moderate for mesangial hypercellularity and poor for endocapillary hypercellularity.’3.Roberts I.S. Pathology of IgA nephropathy.Nat Rev Nephrol. 2014; 10: 445-454Crossref PubMed Scopus (138) Google Scholar In other words, in the absence of a pathology review board, assessment of histological data is suboptimal; yet, this is what guides the routine diagnostic practice. If the predictive value (if even it were investigated) of all our measurements and biopsies is as weak as it appears from this great endeavor, then we certainly appear to look in the wrong places, both for explanation and for prediction.4.Kiryluk K. Novak J. The genetics and immunobiology of IgA nephropathy.J Clin Invest. 2014; 124: 2325-2332Crossref PubMed Scopus (138) Google Scholar