Early Urinary CCL2 is Associated With the Later Development of Interstitial Fibrosis and Tubular Atrophy in Renal Allografts

Introduction: The prevalence of chronic kidney disease (CKD) is high among kidney neoplasm patients because of the overlapping risk factors. Our purpose is to identify kidney cancer survivors with higher CKD risk. Methods: We studied a retrospective cohort of 361 kidney tumor patients with partial or radical nephrectomy. Linear mixed model was performed. Results: Of patients with follow-up >3 months, 84% were identified retrospectively to fulfill criteria for CKD diagnosis, although CKD was documented in only 15%. Urinalysis was performed in 205 (57%) patients at the time of nephrectomy. Multivariate analysis showed interstitial fibrosis and tubular atrophy (IFTA) >25% ( p = 0.005), severe arteriolar sclerosis ( p = 0.013), female gender ( p = 0.024), older age ( p = 0.012), BMI ⩾ 25 kg/m2 ( p < 0.001), documented CKD ( p < 0.001), baseline eGFR ⩽ 60 ml/min/1.73 m2 ( p < 0.001), and radical nephrectomy ( p < 0.001) were independent risk factors of lower eGFR at baseline and during follow-up. Average eGFR decreased within 3 months post nephrectomy. However, patients with different risk levels showed different eGFR time trend pattern at longer follow-ups. Multivariate analysis of time × risk factor interaction showed BMI, radical nephrectomy and baseline eGFR had time-dependent impact. BMI ⩾ 25 kg/m2 and radical nephrectomy were associated with steeper eGFR decrease slope. In baseline eGFR > 90 ml/min/1.73 m2 group, eGFR rebounded to pre-nephrectomy levels during extended follow-up. In partial nephrectomy patients with baseline eGFR ⩾ 90 ml/min/1.73 m2 ( n = 61), proteinuria ( p < 0.001) and BMI ( p < 0.001) were independent risk factors of decreased eGFR during follow up. Conclusions: As have been suggested by others and confirmed by our study, proteinuria and CKD are greatly under-recognized. Although self-evident as a minimum workup for nephrectomy patients to include SCr, eGFR, urinalysis, and proteinuria, the need for uniform applications of this practice should be reinforced. Non-neoplastic histology evaluation is valuable and should include an estimate of global sclerosis% (GS) and IFTA%. Patients with any proteinuria and/or eGFR ⩽ 60 at the time of nephrectomy or in follow-up with urologists, and/or >25% GS or IFTA, should be referred for early nephrology consultation.

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Hyperuricemia and hypertriglyceridemia indicate tubular atrophy/interstitial fibrosis in patients with IgA nephropathy and membranous nephropathy

International Urology and Nephrology ◽

10.1007/s11255-021-02844-4 ◽

2021 ◽

Author(s):

Bingman Liu ◽

Liangyu Zhao ◽

Qingqing Yang ◽

Dongqing Zha ◽

Xiaoyun Si

Keyword(s):

Iga Nephropathy ◽

Membranous Nephropathy ◽

Interstitial Fibrosis ◽

Tubular Atrophy

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Cellular Mechanisms of Tissue Fibrosis. 3. Novel mechanisms of kidney fibrosis

AJP Cell Physiology ◽

10.1152/ajpcell.00414.2012 ◽

2013 ◽

Vol 304 (7) ◽

pp. C591-C603 ◽

Cited By ~ 105

Author(s):

Gabriela Campanholle ◽

Giovanni Ligresti ◽

Sina A. Gharib ◽

Jeremy S. Duffield

Keyword(s):

Chronic Kidney Disease ◽

Kidney Disease ◽

Interstitial Fibrosis ◽

Kidney Injury ◽

Innate Immune ◽

Cellular Mechanisms ◽

Tubular Atrophy ◽

Kidney Fibrosis ◽

Capillary Rarefaction ◽

Peritubular Capillaries

Chronic kidney disease, defined as loss of kidney function for more than three months, is characterized pathologically by glomerulosclerosis, interstitial fibrosis, tubular atrophy, peritubular capillary rarefaction, and inflammation. Recent studies have identified a previously poorly appreciated, yet extensive population of mesenchymal cells, called either pericytes when attached to peritubular capillaries or resident fibroblasts when embedded in matrix, as the progenitors of scar-forming cells known as myofibroblasts. In response to sustained kidney injury, pericytes detach from the vasculature and differentiate into myofibroblasts, a process not only causing fibrosis, but also directly contributing to capillary rarefaction and inflammation. The interrelationship of these three detrimental processes makes myofibroblasts and their pericyte progenitors an attractive target in chronic kidney disease. In this review, we describe current understanding of the mechanisms of pericyte-to-myofibroblast differentiation during chronic kidney disease, draw parallels with disease processes in the glomerulus, and highlight promising new therapeutic strategies that target pericytes or myofibroblasts. In addition, we describe the critical paracrine roles of epithelial, endothelial, and innate immune cells in the fibrogenic process.

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Is mycophenolate mofetil combined with low-dose prednisone a treatment option for advanced IgA nephropathy? A 10-year follow-up case and brief literature review

European Journal of Inflammation ◽

10.1177/2058739218802680 ◽

2018 ◽

Vol 16 ◽

pp. 205873921880268

Author(s):

Qijun Wan ◽

Yongcheng He ◽

Hongtao Chen ◽

Hongping Liu ◽

Saodong Luan ◽

...

Keyword(s):

Mycophenolate Mofetil ◽

Iga Nephropathy ◽

Treatment Option ◽

Low Dose ◽

Interstitial Fibrosis ◽

Immunosuppressive Treatment ◽

Channel Blockers ◽

Tubular Atrophy ◽

Dose Prednisone

IgA nephropathy (IgAN) is now widely recognized as the most common primary glomerulonephritis worldwide, especially in China. The immunosuppressive treatment option for IgAN is still controversial. Previously, we proved that mycophenolate mofetil (MMF; Shanghai Roche, China) combined with low-dose prednisone was an effective and safe option for biopsy-proven mild to moderate IgAN patients in a short term of follow-up. This article we first reported the safety and efficacy of this regimen in a 42-year-old male biopsy-proven advanced 10-year follow-up IgAN case (Lee’s Class V; the patient was biopsied 10 years ago, so the Oxford Mesangial hypercellularity Endocapillary hypercellularity Segmental glomerulosclerosis Tubular atrophy/interstitial fibrosis (MEST) classification was not used). The mycophenolate and prednisone were only given for a limited time. The other main medications included calcium channel blockers and antiplatelet agents. Clinical and laboratory indexes were aperiodic assessed during the 10-year follow-up. The serum creatinine decreased from 356 to around 210 μmol/L and urine excretion protein reduced from 3.4 g/d to about 0.5 g/d after 6 months of the initiation of this regimen, respectively. These perfect treatment effects could maintain well during the whole follow-up period. No obvious complications were observed.

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In Patients with Membranous Lupus Nephritis, Exostosin-Positivity and Exostosin-Negativity Represent Two Different Phenotypes

Journal of the American Society of Nephrology ◽

10.1681/asn.2020081181 ◽

2021 ◽

pp. ASN.2020081181 ◽

Cited By ~ 1

Author(s):

Aishwarya Ravindran ◽

Marta Casal Moura ◽

Fernando C. Fervenza ◽

Samih H. Nasr ◽

Mariam P. Alexander ◽

...

Keyword(s):

Lupus Nephritis ◽

Kidney Biopsy ◽

Interstitial Fibrosis ◽

Study Cohort ◽

Lower Serum ◽

Tubular Atrophy ◽

Novel Proteins ◽

Biopsy Specimens ◽

Membranous Lupus Nephritis

BackgroundIn patients with secondary (autoimmune) membranous nephropathy, two novel proteins, Exostosin 1 and Exostosin 2 (EXT1/EXT2), are potential disease antigens, biomarkers, or both. In this study, we validate the EXT1/EXT2 findings in a large cohort of membranous lupus nephritis.MethodsWe conducted a retrospective cohort study of patients with membranous lupus nephritis, and performed immunohistochemistry studies on the kidney biopsy specimens against EXT1 and EXT2. Clinicopathologic features and outcomes of EXT1/EXT2-positive versus EXT1/EXT2-negative patients were compared.ResultsOur study cohort included 374 biopsy-proven membranous lupus nephritis cases, of which 122 (32.6%) were EXT1/EXT2-positive and 252 (67.4%) were EXT1/EXT2-negative. EXT1/EXT2-positive patients were significantly younger (P=0.01), had significantly lower serum creatinine levels (P=0.02), were significantly more likely to present with proteinuria ≥3.5 g/24 h (P=0.009), and had significantly less chronicity features (glomerulosclerosis, P=0.001 or interstitial fibrosis and tubular atrophy, P<0.001) on kidney biopsy. Clinical follow-up data were available for 160 patients, of which 64 (40%) biopsy results were EXT1/EXT2-positive and 96 (60%) were EXT1/EXT2-negative. The proportion of patients with class 3/4 lupus nephritis coexisting with membranous lupus nephritis was not different between the EXT1/EXT2-positive and EXT1/EXT2-negative groups (25.0% versus 32.3%; P=0.32). The patients who were EXT1/EXT2-negative evolved to ESKD faster and more frequently compared with EXT1/EXT2-positive patients (18.8% versus 3.1%; P=0.003).ConclusionsThe prevalence of EXT1/EXT2 positivity was 32.6% in our cohort of membranous lupus nephritis. Compared with EXT1/EXT2-negative membranous lupus nephritis, EXT1/EXT2-positive disease appears to represent a subgroup with favorable kidney biopsy findings with respect to chronicity indices. Cases of membranous lupus nephritis that are EXT1/EXT2-negative are more likely to progress to ESKD compared with those that are EXT1/EXT2-positive.

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Clinicopathologic Features of Infection-Related Glomerulonephritis with IgA Deposits: a French Nationwide Study

10.21203/rs.2.22607/v2 ◽

2020 ◽

Author(s):

Elodie Miquelestorena-Standley ◽

Charlotte Jaulerry ◽

Marie-Christine Machet ◽

Nolwenn Rabot ◽

Christelle Barbet ◽

...

Keyword(s):

Interstitial Fibrosis ◽

Outcome Data ◽

Renal Outcome ◽

Tubular Atrophy ◽

Short Delay ◽

Adult Men ◽

Staphylococcus Infections ◽

Endocapillary Proliferative Glomerulonephritis ◽

Stage Renal Disease ◽

End Stage

Abstract Background: Infection-related glomerulonephritis with IgA deposits (IRGN-IgA) is a rare disease but it is increasingly reported in the literature. Data regarding epidemiology and outcome are lacking, especially in Europe. We aimed to assess the clinical, pathologic and outcome data of IRGN-IgA. Methods: Clinical and outcome data from patients from 11 French centers over the 2007-2017 period were collected retrospectively. We reviewed pathologic patterns and immunofluorescence of renal biopsies and evaluated C4d expression in IRGN-IgA. We analyzed the correlation between histological presentation and outcome. Results: Twenty-seven patients (23 men, mean age: 62±15 years) were included. Twenty-one (78%) had Staphylococcus aureus infection and twelve (44%) were diabetic. At the time of biopsy, 95.2% had haematuria, 48.1% had a serum creatinine level of >4 mg/dL, and 16% had hypocomplementemia. The most common pathologic presentation included mesangial (88.9%) and endocapillary proliferative glomerulonephritis (88.9%) with interstitial fibrosis and tubular atrophy (IF/TA) (85.1%). Diffuse and global glomerular C4d expression was found in 17.8%, mostly in biopsies with acute or subacute patterns, and was associated with a short delay between infection and renal biopsy compared to segmental and focal staining. After median follow-up of 13.2 months, 23.1% died, 46.2% had persistent renal dysfunction and 15.4% reached end-stage renal disease. Renal outcome was correlated to IF/TA severity. Conclusions: Infection-related glomerulonephritis with IgA deposits is usually associated with Staphylococcus infections and mainly affects adult men. This entity has a poor prognosis which is correlated to interstitial fibrosis and tubular atrophy severity.

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