Association of Treatment Effects on Early Change in Urine Protein and Treatment Effects on GFR Slope in IgA Nephropathy: An Individual Participant Meta-analysis

Inker, Lesley A.; Heerspink, Hiddo J L; Tighiouart, Hocine; Chaudhari, Juhi; Miao, Shiyuan; Diva, Ulysses; Mercer, Alex; Appel, Gerald B.; Donadío, James V.; Floege, Jürgen; Li, Philip K.T.; Maes, Bart; Locatelli, Francesco; Praga, Manuel; Schena, Francesco Paolo; Levey, Andrew S.; Greene, Tom

doi:10.1053/j.ajkd.2021.03.007

Cited by 39 publications

(31 citation statements)

References 45 publications

(75 reference statements)

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“…Recognizing this, expert and regulatory agency recommendations consider decline in eGFR over time (“eGFR slope”) and sustained rises in serum creatinine (>40 or >50%) to be more reliable surrogate end points for kidney failure than change in albuminuria [52]. Nevertheless, given its ease of measurement, and central importance to the pathophysiology of many kidney diseases, especially diabetic kidney disease and glomerulonephritis, reduction in proteinuria will remain a key treatment goal in nephrology [53, 54].…”

Section: Treatment Of Proteinuriamentioning

confidence: 99%

From Proteinuria to Fibrosis: An Update on Pathophysiology and Treatment Options

Sharma

Smyth

2021

Kidney Blood Press Res

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Background: Proteinuria is a key biomarker in nephrology. It is central to diagnosis and risk assessment and the primary target of many important therapies. Etiologies resulting in pathological proteinuria include congenital and acquired disorders, as well as both glomerular (immune/non-immune mediated) and tubular defects. Summary: Untreated proteinuria is strongly linked to progressive loss of kidney function and kidney failure. Excess protein reaching the renal tubules is ordinarily resorbed by the tubular epithelium. However, when these mechanisms are overwhelmed, a variety of inflammatory and fibrotic pathways are activated, causing both interstitial fibrosis and glomerulosclerosis. Nevertheless, the specific mechanisms underlying this are complex and remain incompletely understood. Recently, a number of treatments, in addition to angiotensin system blockade, have been shown to effectively slow the progression of proteinuric chronic kidney disease. However, additional therapies are clearly needed. Key message: This review provides an update on the pathophysiology of proteinuria, the pathways leading to fibrosis, and an overview of current and emerging therapies.

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Section: Treatment Of Proteinuriamentioning

confidence: 99%

From Proteinuria to Fibrosis: An Update on Pathophysiology and Treatment Options

Sharma

Smyth

2021

Kidney Blood Press Res

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“…Although there was no statistical significance, baseline and changes in urinary C5b-9 levels tended to be negatively correlation with baseline eGFR and the mean annual rate of eGFR decline, respectively. A decrease in proteinuria typically occurred within months after treatment, whereas demonstration of differences in eGFR decline required much longer follow-up in studies on the clinical outcomes of IgAN [40,41]. The mean follow-up duration of enrolled patients in the current study was 3.4 years; however, it may have been too short to establish an association between urinary C5b-9 levels and eGFR.…”

Section: Discussionmentioning

confidence: 84%

“…A negative correlation was observed between changes in urinary C5b-9 levels and changes in eGFR six months after medical treatment. Considering that a recent study provides a rigorous foundation for the use of proteinuria reduction as an endpoint in IgAN [40], although urinary C3b-9 levels were associated with a decrease in proteinuria alone, urinary C5b-9 levels might be considered as a prognostic factor in IgAN. Although there was no statistical significance, baseline and changes in urinary C5b-9 levels tended to be negatively correlation with baseline eGFR and the mean annual rate of eGFR decline, respectively.…”

Section: Discussionmentioning

confidence: 99%

Urinary C5b-9 as a Prognostic Marker in IgA Nephropathy

Park

Lee

et al. 2022

JCM

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C5b-9 plays an important role in the pathogenesis of immunoglobin A nephropathy (IgAN). We evaluated C5b-9 as a prognostic marker for IgAN. We prospectively enrolled 33 patients with biopsy-proven IgAN. We analyzed the correlation between baseline urinary C5b-9 levels, posttreatment changes in their levels, and clinical outcomes, including changes in proteinuria, estimated glomerular filtration rate (eGFR), and treatment response. Baseline urinary C5b-9 levels were positively correlated with proteinuria (r = 0.548, p = 0.001) at the time of diagnosis. Changes in urinary C5b-9 levels were positively correlated with changes in proteinuria (r = 0.644, p < 0.001) and inversely correlated with changes in eGFR (r = −0.410, p = 0.018) at 6 months after treatment. Changes in urinary C5b-9 levels were positively correlated with time-averaged proteinuria during the follow-up period (r= 0.461, p = 0.007) but were not correlated with the mean annual rate of eGFR decline (r = −0.282, p = 0.112). Baseline urinary C5b-9 levels were not a significant independent factor that could predict the treatment response in logistic regression analyses (odds ratio 0.997; 95% confidence interval, 0.993 to 1.000; p = 0.078). Currently, urinary C5b-9 is not a promising prognostic biomarker for IgAN, and further studies are needed.

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“…In addition to the diagnostic value, we further investigated the clinical significance of these urinary sediment miRNAs. Proteinuria, eGFR and Oxford classification were all closely associated with the progression and prognosis of IgAN [12][13][14] . In our results, miR-16-5p levels were significantly higher in the urine sediment of patients with E1 in contrast to E0 patients, and blood complement C4 levels were lower in E1 compared with E0 patients, further confirming that endocapillary hypercellularity is a hallmark of active inflammation 15 and that endothelial cell proliferation is primarily the result of inflammatory cell infiltration 16 .…”

Section: Discussionmentioning

confidence: 95%

Urinary miR-16-5p can be used as a potential marker of endocapillary hypercellularity in IgA nephropathy

Zhang

Duan

Zhang

et al. 2023

Sci Rep

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The most prevalent primary glomerulonephritis and leading cause of end-stage renal disease worldwide is IgA nephropathy (IgAN). More and more studies are describing urinary microRNA (miRNA) as a non-invasive marker for a variety of renal diseases. We screened candidate miRNAs based on data from three published IgAN urinary sediment miRNAs chips. In separate confirmation and validation cohorts, we included 174 IgAN patients, 100 patients with other nephropathies as disease controls (DC), and 97 normal controls (NC) for quantitative real-time PCR. A total of three candidate miRNAs, miR-16-5p, Let-7g-5p, miR-15a-5p were obtained. In both the confirmation and validation cohorts, these miRNAs levels were considerably higher in the IgAN than in NC, with miR-16-5p significantly higher than in DC. The area under the ROC curve for urinary miR-16-5p levels was 0.73. Correlation analysis suggested that miR-16-5p was positively correlated with endocapillary hypercellularity (r = 0.164 p = 0.031). When miR-16-5p was combined with eGFR, proteinuria and C4, the AUC value for predicting endocapillary hypercellularity was 0.726. By following the renal function of patients with IgAN, the levels of miR-16-5p were noticeably higher in the IgAN progressors than in the non- progressors (p = 0.036). Urinary sediment miR-16-5p can be used as noninvasive biomarkers for the assessment of endocapillary hypercellularity and diagnosis of IgA nephropathy. Furthermore, urinary miR-16-5p may be predictors of renal progression.

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Association of Treatment Effects on Early Change in Urine Protein and Treatment Effects on GFR Slope in IgA Nephropathy: An Individual Participant Meta-analysis

Cited by 39 publications

References 45 publications

From Proteinuria to Fibrosis: An Update on Pathophysiology and Treatment Options

From Proteinuria to Fibrosis: An Update on Pathophysiology and Treatment Options

Urinary C5b-9 as a Prognostic Marker in IgA Nephropathy

Urinary miR-16-5p can be used as a potential marker of endocapillary hypercellularity in IgA nephropathy

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