Histological predictors for renal prognosis in diabetic nephropathy in diabetes mellitus type 2 patients with overt proteinuria

Okada, Tomonari; Nagao, Toshitaka; Matsumoto, Hiroshi; Nagaoka, Yume; Wada, Toshikazu; Nakao, Toshiyuki

doi:10.1111/j.1440-1797.2011.01525.x

Cited by 90 publications

(89 citation statements)

References 29 publications

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“…not only a glomerular lesion, but also IFTA and interstitial inflammation had a strong impact on the renal prognosis [7] . Several other reports have also suggested the importance of these pathological lesions in assessing the renal outcome [8,10,16] . Nevertheless, because the correlation between organ changes in the kidney is so complex [7] , the net effect of kidney damage on renal prognosis remained unknown.…”

Section: Discussionmentioning

confidence: 99%

“…Several large studies showed that a high urinary albumin-to-creatinine ratio and a low estimated glomerular filtration rate (eGFR) are predictors for diabetic ESRD and death [2][3][4][5] . In addition to these clinical parameters, after the development of pathological classification of DN by Tervaert et al [6] , several studies suggested that both glomerular and interstitial damage are independently associated with ESRD [7][8][9][10] . But it remained unknown how much the separate sorts of damage revealed by renal biopsy -with varying degrees of severity for each patientimpact the overall renal outcome.…”

Section: A Pathological Scoring System To Predict Renal Outcome In DImentioning

confidence: 99%

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A Pathological Scoring System to Predict Renal Outcome in Diabetic Nephropathy

et al. 2015

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Background: With the association between diabetic nephropathy (DN) and renal outcome being increasingly clear, we aimed at creating a new DN pathological scoring system that could predict the renal outcome. Methods: We studied 205 patients with DN confirmed by renal biopsy, sometime between March 1985 and January 2010, who met the inclusion criteria. Renal biopsy included clinical parameters and Tervaert classifications. Hazard ratios (HRs) for death-censored end-stage renal disease (ESRD) were estimated by adjusted Cox proportional-hazards regression. The overall pathological risk score (D-score) was calculated by summing the products of beta coefficient and bootstrap-inclusion fractions, its predictive utility evaluated by Kaplan-Meier methods and c-statistics for a 10-year risk of ESRD. Results: The D-scores of glomerular classes 1, 2A, 2B, 3, and 4 were, respectively, 0, 3, 4, 6, and 6. Those of interstitial fibrosis and tubular atrophy classes 0, 1, 2, and 3 were 0, 7, 9, and 11, and those of interstitial inflammation classes 0, 1, and 2 were 0, 3, and 4, respectively. The D-score of hyalinosis class 2 was 3 and that of arteriosclerosis class 2 was 1. So, a patient's D-score could be 0-25. HRs for ESRD in patients with D-score ≤14, 15-18, 19-21, and 22-25 were, respectively, 1.00 (reference) 16.21 (95% confidence interval (CI), 1.86-140.90), 19.78 (95% CI, 2.15-182.40), and 45.46 (95% CI, 4.63-446.68) after adjusting for clinical factors. The c-statistics suggested a better predictive ability for a 10-year renal death with models that included the D-score. Conclusion: Prediction of DN patients' renal outcome was better with the D-score than without it. Patients with a D-score ≤14 had excellent renal prognosis.

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Section: Discussionmentioning

confidence: 99%

Section: A Pathological Scoring System To Predict Renal Outcome In DImentioning

confidence: 99%

A Pathological Scoring System to Predict Renal Outcome in Diabetic Nephropathy

et al. 2015

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“…The area of TI fibrosis was slightly lower (16.8%) in the 2K-obese ZSF-1 group compared to the 1K-obese rats at the 24-week point of the study. A relationship between the development of TI fibrosis and a decline in GFR and/or patient survival has been controversial with studies presenting evidence on either side of this putative linkage [24,25,26,27], but a recent large scale study with DN patients demonstrated a strong link between interstitial fibrosis and renal outcome independent of other clinical features [28]. In the same study, glomerular lesions were also associated with renal outcome and correlated with the development of interstitial fibrosis.…”

Section: Discussionmentioning

confidence: 99%

Longitudinal Changes in Measured Glomerular Filtration Rate, Renal Fibrosis and Biomarkers in a Rat Model of Type 2 Diabetic Nephropathy

Widomski

et al. 2016

Am J Nephrol

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Background: Obese ZSF-1 rats display many features of human type II diabetes including nephropathy (DN). The study aimed to further understand the relevance of this model to DN, for which glomerular filtration rate (GFR), renal fibrosis and several urinary/tissue biomarkers was followed over 24 weeks in ZSF-1 rats. Methods: Intact/sham or uninephrectomized male and female ZSF-1 rats were studied. GFR was measured by transdermal clearance of fluorescein isothiocyanate-sinistrin. Urine was collected every 2-4 weeks for biomarker analysis. Renal tissue was examined histologically for fibrosis and for levels of inflammatory and fibrotic genes. Results: Male obese ZSF-1 rats demonstrated metabolic syndrome and proteinuria. Female counterparts were hyperlipidemic with delayed proteinuria, but were not hyperglycemic. Kidney hyperfiltration was observed in male obese rats in weeks 2-4 after surgery, and subsequently declined to levels significantly lower than controls. Tubulointerstitial/glomerular fibrosis in male obese rats was significantly elevated by week 12 post surgery and continued to expand in the ensuing weeks, particularly in uninephrectomized rats. Female rats had less severe fibrosis. Except for epidermal growth factor which decreased, the levels of several key inflammatory, injury and fibrotic factors were elevated in both tissue (mRNA) and urine (protein) of male obese rats. Conclusion: Male obese ZSF-1 rats represent an important DN model, manifesting key pathophysiological features including metabolic syndrome, proteinuria, progressive tubular and glomerular fibrosis, and transient hyperfiltration followed by progressive decline in renal function. Uninephrectomy significantly accelerated disease progression. Females were less severe in disease manifestation. Several urinary and tissue biomarkers were identified in the male obese rats that tracked with disease progression.

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“…Several studies have indicated that changes in the tubulointerstitial tissue compartment are a prominent feature of the pathophysiologic processes that lead to progression of kidney disease. First, the clinical kidney outcome of ESRD, for which dialysis or a renal transplantation is needed, is predicted by the severity of glomerular lesions but more strongly predicted by the severity of tubulointerstitial damage (tubular atrophy, interstitial inflammation, and interstitial fibrosis) (9). Second, numerous in vitro and in vivo studies have reported that increased glomerular albumin leakage stimulates proinflammatory and profibrotic signals that directly contribute to tubulointerstitial damage.…”

Section: Albumin Leakage Causes Renal Damagementioning

confidence: 99%

Albuminuria Is an Appropriate Therapeutic Target in Patients with CKD

Heerspink¹,

Gansevoort

2015

Clinical Journal of the American Society of Nephrology

136

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The presence of elevated levels of albuminuria is associated with an increased risk of progressive renal function loss over time. This association is found in various pathophysiological conditions, including diabetic nephropathy, hypertensive nephropathy, and various primary renal diseases, but also, the general, otherwise healthy population. Emerging data report that elevated albuminuria causes tubulointerstitial damage through activation of proinflammatory mediators, which ultimately leads to a progressive decline in renal function. Nowadays, various drugs are available that decrease the rate of GFR loss in patients with kidney disease. Well known are renin-angiotensin-aldosterone system inhibitors, but there are also other drugs and interventions, like intensive glucose control, anti-inflammatory agents (pentoxifylline), or a low-protein diet. These interventions have an additional effect beyond their original target, namely lowering albuminuria. Analyses from clinical trials show that the reduction in albuminuria observed during the first months of treatment with these drugs correlates with the degree of long-term renal protection: the larger the initial reduction in albuminuria, the lower the risk of ESRD during treatment. In addition, in treated patients, residual albuminuria is again the strongest risk marker for renal disease progression. These observations combined provide a strong argument that albuminuria is an appropriate therapeutic target in patients with CKD.

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Histological predictors for renal prognosis in diabetic nephropathy in diabetes mellitus type 2 patients with overt proteinuria

Abstract: Interstitial lesions but not glomerular lesions were a significant predictor for renal prognosis in diabetic nephropathy in type 2 diabetes patients with overt proteinuria.

Cited by 90 publications

References 29 publications

A Pathological Scoring System to Predict Renal Outcome in Diabetic Nephropathy

A Pathological Scoring System to Predict Renal Outcome in Diabetic Nephropathy

Longitudinal Changes in Measured Glomerular Filtration Rate, Renal Fibrosis and Biomarkers in a Rat Model of Type 2 Diabetic Nephropathy

Albuminuria Is an Appropriate Therapeutic Target in Patients with CKD

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