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Since the Oxford Classification of IgA nephropathy (IgAN) was published in 2009, MEST scores have been increasingly used in clinical practice. Further retrospective cohort studies have confirmed that in biopsy specimens with a minimum of 8 glomeruli, mesangial hypercellularity (M), segmental sclerosis (S), and interstitial fibrosis/tubular atrophy (T) lesions predict clinical outcome. In a larger, more broadly based cohort than in the original Oxford study, crescents (C) are predictive of outcome, and we now recommend that C be added to the MEST score, and biopsy reporting should provide a MEST-C score. Inconsistencies in the reporting of M and endocapillary cellularity (E) lesions have been reported, so a web-based educational tool to assist pathologists has been developed. A large study showed E lesions are predictive of outcome in children and adults, but only in those without immunosuppression. A review of S lesions suggests there may be clinical utility in the subclassification of segmental sclerosis, identifying those cases with evidence of podocyte damage. It has now been shown that combining the MEST score with clinical data at biopsy provides the same predictive power as monitoring clinical data for 2 years; this requires further evaluation to assess earlier effective treatment intervention. The IgAN Classification Working Group has established a well-characterized dataset from a large cohort of adults and children with IgAN that will provide a substrate for further studies to refine risk prediction and clinical utility, including the MEST-C score and other factors.
Background Large trials have shown sodium glucose co-transporter-2 (SGLT2) inhibitors reduce risk of kidney and cardiovascular outcomes in patients with heart failure and chronic kidney disease (CKD), but were not powered to assess outcomes in patients with and without diabetes separately. Methods We did a meta-analysis of large placebo-controlled SGLT2 inhibitor trials (PROSPERO:CRD42022351618). The main outcomes were kidney disease progression (standardised to a definition of a sustained ≥50% decline in estimated glomerular filtration rate (eGFR), end-stage kidney disease, or death from kidney failure), acute kidney injury (AKI), mortality and the composite of cardiovascular death or hospitalisation for heart failure. Findings 13 trials involving a total of 90,413 participants were included (15,605 [17%] without diabetes; trial average baseline eGFR range: 37-85 ml/min/1·73m 2 ). Compared with placebo, allocation to an SGLT2 inhibitor reduced the risk of kidney disease progression by 37% (relative risk [RR] 0·63, 95% confidence interval 0·58-0·69) with similar RRs in patients with and without diabetes (heterogeneity p=0·31). In the 4 CKD trials, RRs were similar irrespective of primary kidney diagnoses (heterogeneity p=0·67). SGLT2 inhibitors reduced the risk of AKI by 23% (0·77, 0·70-0·84) and the risk of cardiovascular death or hospitalisation for heart failure by 23% (0·77, 0·74-0·81), again with similar effects in those with and without diabetes (heterogeneity p values=0·12 and 0·67, respectively. Allocation to an SGLT2 inhibitor did not significantly reduce the risk of non-cardiovascular death (0·94, 0·88-1·02), with similar RRs in patients with or without diabetes. For all outcomes, results were also broadly similar irrespective of trial-average baseline eGFR (all trend tests p>0·05). In the trial populations studied to date, the absolute benefits of SGLT2-inhibition outweigh any serious hazards. Interpretation The totality of the randomised data supports the use of SGLT2 inhibitors to modify risk of kidney disease progression and AKI, not only in patients with type 2 diabetes, but also in patients with CKD or heart failure irrespective of diabetes status, primary kidney disease or kidney function. Funding MRC-UK&KRUK.
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