The association of hematuria on kidney clinicopathologic features and renal outcome in patients with diabetic nephropathy: a biopsy-based study

Wu, Yucheng; Zhang, J; Wang, Y; Wang, T; Han, Qianqian; Guo, Renhua; Zhang, R; Ren, Honghong; Zhu, Yitao; Xu, Hong‐Xi; Li, L; Tong, Nanwei; Liu, F

doi:10.1007/s40618-020-01207-7

Cited by 13 publications

(17 citation statements)

References 27 publications

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“…A more recent clinical study reported that hematuria in patients with biopsy-proven diabetic nephropathy was associated with advanced renal pathology and a higher risk of ESKD. 18 However, this study did not demonstrate whether the effect of hematuria on ESKD was independent of renal pathology.…”

Section: Discussioncontrasting

confidence: 59%

“…A recent study recruited patients with biopsy-proven diabetic nephropathy also showed that the level of proteinuria was higher in the patients with hematuria. 18 Another study in patients with biopsy-proven diabetic nephropathy reported that the presence of hematuria was associated with the presence of nephrotic syndrome. 19 Considering the pathological findings in renal biopsy, hematuria accompanied by proteinuria reflected advanced stages of diabetic nephropathy.…”

Section: Discussionmentioning

confidence: 99%

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Microscopic hematuria is a risk factor for end-stage kidney disease in patients with biopsy-proven diabetic nephropathy

Okada

Samejima

Matsui³

et al. 2020

BMJ Open Diab Res Care

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IntroductionThere are fewer reports about whether the presence of hematuria affects the progression of chronic kidney disease in patients with diabetic nephropathy. We analyzed whether microscopic hematuria in diabetic nephropathy is a risk factor for end-stage kidney disease (ESKD).Research design and methodsThe present study was a retrospective cohort study of patients with biopsy-proven diabetic nephropathy. We recruited 397 patients with diabetic nephropathy, which was confirmed by renal biopsy between June 1981 and December 2014 and followed them until October 2018 or death. Patients with microscopic hematuria before renal biopsy were defined as the hematuria group (n=91), and the remainder as the no-hematuria group (n=306). The main outcome was the occurrence of ESKD, which was defined by the requirement of permanent renal replacement therapies.ResultsThe systolic and diastolic blood pressure, serum creatinine and proteinuria were significantly higher, and the estimated glomerular filtration rate was significantly lower in the hematuria group compared with the no-hematuria group. Pathological evaluations revealed that glomerular, tubulointerstitial and vascular lesions in the hematuria group were significantly more severe. During a median of 10.1 years, 44 and 52 patients developed ESKD in the hematuria group and the no-hematuria group, respectively. Survival analyses showed that the incidence of ESKD was significantly higher in the hematuria group compared with the no-hematuria group (log-rank, p<0.0001). The multivariable Cox proportional hazards models revealed a significant association between hematuria and the incidence of ESKD after adjusting for clinically relevant factors, including proteinuria and renal pathology (adjusted HR 1.64, 95% CI 1.03 to 2.60). The subgroups of men, proteinuria ≥0.5 g/day, and systolic blood pressure ≥132 mm Hg showed a stronger association between hematuria and ESKD than their opposing subgroups.ConclusionsMicroscopic hematuria is a risk factor for ESKD in diabetic nephropathy, independent of proteinuria and renal pathology.

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Section: Discussioncontrasting

confidence: 59%

Section: Discussionmentioning

confidence: 99%

Microscopic hematuria is a risk factor for end-stage kidney disease in patients with biopsy-proven diabetic nephropathy

Okada

Samejima

Matsui³

et al. 2020

BMJ Open Diab Res Care

View full text Add to dashboard Cite

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“…We did not identify differences between our groups in the proportion of patients with microhematuria, and we presently consider it as a rather unspecific finding in patients with DM and kidney dysfunction and/or proteinuria. Moreover, a recent study on 261 patients with biopsy-proven DKD demonstrated the presence of hematuria in almost half of them [17]; interestingly, hematuria was associated with more severe histological damage and predicted a worse prognosis in this cohort.…”

Section: Discussionmentioning

confidence: 71%

Clinical Predictors of Nondiabetic Kidney Disease in Patients with Diabetes: A Single-Center Study

Fontana

Perrone

Giaroni

et al. 2021

International Journal of Nephrology

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Background. Although diabetic kidney disease (DKD) could affect up to one-third of patients with diabetes mellitus (DM), these patients can develop kidney diseases different from DKD, or these conditions can superimpose on DKD. Several potential predictors of nondiabetic kidney disease (NDKD) have been proposed, but there are no definitive indications available for kidney biopsy in diabetic patients. Methods. We designed a single-center, cross-sectional, and retrospective cohort study to identify clinical and laboratory factors associated with a diagnosis of NDKD after native kidney biopsy in diabetic patients and to investigate differences in time to end-stage kidney disease (ESKD) in patients with a diagnosis of DKD and NDKD. Results. Of 142 patients included in our analysis, 89 (62.68%) had a histopathological diagnosis of NDKD or mixed NDKD + DKD. Patients in the NDKD group had significantly lower HbA1C, lower prevalence of diabetic retinopathy (DR), and less severe proteinuria, and there was a lower proportion of patients with nephrotic syndrome; the DKD group had significantly lower proportion of patients with hematological conditions. In the multivariate binary logistic regression, only absence of DR and presence of a hematological condition significantly predicted NDKD after adjustment for age and sex. Time to ESKD was significantly higher in patients with NDKD or mixed forms than in those with DKD. Conclusions. After a careful selection, more than half of kidney biopsies performed in diabetic patients can identify NDKD (alone or with concomitant DKD). Absence of DR and coexistence of a hematological condition (especially MGUS) were strong predictors of NDKD in our cohort.

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“…Diabetic nephropathy (DN) is a type of end-stage renal disease that accounts for approximately 16.4% of all diabetes cases in China [1] and afflicts more than 20-40% of patients with diabetes globally [2]. Although glomerular lesions are the major cause of DN, many studies have demonstrated that tubular injury, which is attributable to epithelial-mesenchymal transition (EMT) [3,4], has a significant role in DN [5][6][7][8][9][10][11]. However, the understanding of the underlying pathogenesis of tubular injury in DN remains incomplete.…”

Section: Introductionmentioning

confidence: 99%

FOXO3a Protects against Kidney Injury in Type II Diabetic Nephropathy by Promoting Sirt6 Expression and Inhibiting Smad3 Acetylation

Wang

et al. 2021

Oxidative Medicine and Cellular Longevity

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Diabetic nephropathy (DN) is the most common cause of end-stage renal disease. Although numerous reports have demonstrated a correlation between epithelial-mesenchymal transition (EMT) and renal fibrosis, how these processes lead to tubular dysfunction remains unclear. Here, we show that FOXO3a protects kidneys from injury in type II DN by increasing Sirt6 expression, which deacetylates Smad3 and inhibits its transcriptional activity. The results showed that progressive EMT in the kidneys from db/db mice is associated with Sirt6 downregulation and involved in tubular injury and dysfunction. The reduction of Sirt6 levels in db/db mice resulted in progressive kidney injury, indicating the protective role of Sirt6. Furthermore, Sirt6 was shown to directly bind to Smad3, a key downstream mediator of TGF-β, and could deacetylate it to inhibit its nuclear accumulation and transcriptional activity in HK2 cells. Besides, we demonstrate that FOXO3a activates Sirt6 expression by binding to its promoter. shRNA-induced FOXO3a knockdown in the kidneys of db/db mice exacerbated tubular injury and renal function loss. Mechanistically, FOXO3a protects against kidney injury in type II DN through the Sirt6/Smad3 axis. Thus, the pharmacological targeting of FOXO3a-mediated Sirt6/Smad3 signaling pathways may provide a novel strategy for treating type II DN.

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The association of hematuria on kidney clinicopathologic features and renal outcome in patients with diabetic nephropathy: a biopsy-based study

Cited by 13 publications

References 27 publications

Microscopic hematuria is a risk factor for end-stage kidney disease in patients with biopsy-proven diabetic nephropathy

Microscopic hematuria is a risk factor for end-stage kidney disease in patients with biopsy-proven diabetic nephropathy

Clinical Predictors of Nondiabetic Kidney Disease in Patients with Diabetes: A Single-Center Study

FOXO3a Protects against Kidney Injury in Type II Diabetic Nephropathy by Promoting Sirt6 Expression and Inhibiting Smad3 Acetylation

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