Utilizing the MEST score for prognostic staging in IgA nephropathy

Haaskjold, Yngvar Lunde; Bjørneklett, Rune; Bostad, Leif; Lura, Njål; Knoop, Thomas

doi:10.1186/s12882-021-02653-y

Cited by 16 publications

(14 citation statements)

References 46 publications

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“…Even though the tools are available online, clinicians still must provide both clinical and histopathologic data to use them. As described previously, we found that the MEST score alone performed well as a prognostic model [ 19 ]. This finding could indicate that some clinical parameters, such as blood pressure, proteinuria, and eGFR, fluctuate, which makes them, to some extent, less accurate than histopathologic parameters, given a representative biopsy specimen.…”

Section: Discussionsupporting

confidence: 60%

“…chose to add race to their model and leave out crescents, arguing that crescents are strongly associated with race, and race is a more prominent predictor of ESRD [ 23 ]. We have previously described that even though crescents are independently a strong predictor for progressive decrease in renal function [ 24 ], adding C to the MEST score does not significantly improve its prognostic value [ 19 ]. Notably, the ANN model includes sex as a prognostic factor, which is supported by a recent study describing male sex as a risk factor for IgAN [ 25 ].…”

Section: Discussionmentioning

confidence: 99%

“…In this study, we included 306 patients from a cohort previously used to address the prognostic value of the Oxford Classification [ 19 ]. The patients all had IgAN, proven by biopsy, before 2010, an initial eGFR level above 30 mL/min/1.73 m 2 , and histopathologic specimens that were available for reanalysis according to the Oxford Classification.…”

Section: Methodsmentioning

confidence: 99%

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

Haaskjold

Lura

Bjørneklett

et al. 2022

Nephrology Dialysis Transplantation

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Background Recently, two immunoglobulin A nephropathy prediction tools were developed that combine clinical and histopathological parameters. The International IgAN Prediction Tool predicts the risk for 50% declines in the estimated glomerular filtration rate or end-stage renal 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 renal 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 immunoglobulin A 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 of 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 with 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.

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Section: Discussionsupporting

confidence: 60%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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

Haaskjold

Lura

Bjørneklett

et al. 2022

Nephrology Dialysis Transplantation

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“…Moreover, the T score of the Oxford classification was associated with urinary Gd-IgA1 levels. Previous reports indicated that the T score is associated with a poor renal outcome [ 28 , 29 ]. Of note, the T score was significantly associated with the renal outcome, independently of clinical data [ 30 ].…”

Section: Discussionmentioning

confidence: 99%

Galactose-Deficient IgA1 as a Candidate Urinary Marker of IgA Nephropathy

Fukao

Suzuki

Kim

et al. 2022

JCM

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In patients with IgA nephropathy (IgAN), circulatory IgA1 and IgA1 in the mesangial deposits contain galactose-deficient IgA1 (Gd-IgA1). Some of the Gd-IgA1 from the glomerular deposits is excreted in the urine and thus urinary Gd-IgA1 may represent a disease-specific marker. We recruited 338 Japanese biopsy-proven IgAN patients and 120 patients with other renal diseases (disease controls). Urine samples collected at the time of renal biopsy were used to measure Gd-IgA1 levels using a specific monoclonal antibody (KM55 mAb). Urinary Gd-IgA1 levels were significantly higher in patients with IgAN than in disease controls. Moreover, urinary Gd-IgA1 was significantly correlated with the severity of the histopathological parameters in IgAN patients. Next, we validated the use of urinary Gd-IgA1 levels in the other Asian cohorts. In the Korean cohort, urinary Gd-IgA1 levels were also higher in patients with IgAN than in disease controls. Even in Japanese patients with IgAN and trace proteinuria (less than 0.3 g/gCr), urinary Gd-IgA1 was detected. Thus, urinary Gd-IgA1 may be an early disease-specific biomarker useful for determining the disease activity of IgAN.

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“…The Oxford MEST-C classification, a histopathologic tool assessing mesangial hypercellularity (M), endocapillary hypercellularity (E), segmental glomerulosclerosis (S), tubular atrophy/interstitial fibrosis (T), and cellular/ fibrocellular crescents (C), 16 was documented at baseline from pathology reports. In addition, the degree of complement staining was also documented from pathology reports, if available.…”

Section: End Pointsmentioning

confidence: 99%

Phase 2 Trial of Cemdisiran in Adult Patients with IgA Nephropathy: A Randomized Controlled Trial

Barratt,

Liew,

Yeo

et al. 2024

CJASN

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Background IgA nephropathy is the most common primary GN. Clinical features of IgA nephropathy include proteinuria, which is the strongest known surrogate of progression to kidney failure. Complement pathway activation is a critical driver of inflammation and tissue injury in IgA nephropathy. Cemdisiran is an investigational RNA interference therapeutic that suppresses hepatic production of complement component 5 (C5), thereby potentially reducing proteinuria in IgA nephropathy. We evaluated the efficacy and safety of cemdisiran in adult patients with IgA nephropathy at high risk of kidney disease progression. Methods In this phase 2, 36-week, double-blind study, adult patients with IgA nephropathy and urine protein ≥1 g/24 hours were randomized (2:1) to subcutaneous cemdisiran 600 mg or placebo every 4 weeks in combination with the standard of care. The primary end point was percentage change from baseline at week 32 in urine protein-to-creatinine ratio (UPCR) measured by 24-hour urine collection. Additional end points included change from baseline in UPCR measured by spot urine, serum C5 level, and safety assessments. Results Thirty-one patients were randomized (cemdisiran, N=22; placebo, N=9). Cemdisiran-treated patients had a placebo-adjusted geometric mean change in 24-hour UPCR of –37.4% (cemdisiran-adjusted geometric mean ratio to baseline [SEM], 0.69 [0.10]) at week 32. Spot UPCR was consistent with 24-hour UPCR placebo-adjusted change of –45.8% (cemdisiran-adjusted geometric mean ratio to baseline [SEM], 0.73 [0.11]). Mean (SD) change in serum C5 level from baseline at week 32 was –98.7% (1.2) with cemdisiran and 25.2% (57.7) with placebo. Over 36 weeks, most adverse events were mild or moderate and transient; the most common adverse event after cemdisiran treatment was injection-site reaction (41%). Conclusions These findings indicate that treatment with cemdisiran resulted in a reduction of proteinuria at week 32 and was well tolerated.

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Utilizing the MEST score for prognostic staging in IgA nephropathy

Cited by 16 publications

References 46 publications

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

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

Galactose-Deficient IgA1 as a Candidate Urinary Marker of IgA Nephropathy

Phase 2 Trial of Cemdisiran in Adult Patients with IgA Nephropathy: A Randomized Controlled Trial

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