Nationwide multicentre kidney biopsy study of Japanese patients with type 2 diabetes

Furuichi, Kengo; Yuzawa, Yukio; Shimizu, Miho; Hara, Akinori; Toyama, Tadashi; Kitamura, Hiroshi; Suzuki, Yuichi; Sato, Hiroshi; Uesugi, Noriko; Ubara, Yoshifumi; Hisano, Satoshi; Ueda, Yoshihiko; Nishi, Shinichi; Yokoyama, Hitoshi; Nishino, Tomoya; Kohagura, Kentaro; Ogawa, Daisuke; Mise, Kazuyuki; Shibagaki, Yugo; Kimura, Kenjiro; Haneda, Masakazu; Makino, Hírofumi; Matsuo, Seiichi; Wada, Takashi

doi:10.1093/ndt/gfw417

Cited by 67 publications

(62 citation statements)

References 20 publications

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“…Back in the early 2000s, a biopsy study done in patients with type 1 diabetes showed that typical glomerular features associated with diabetic nephropathy (diabetic glomerulopathy) are often observed in nonproteinuric diabetic kidney disease, although this study did not deeply investigate interstitial and arterial features [18]. Meanwhile, after 2010, biopsy studies in patients with type 2 diabetes showed that typical glomerular features associated with diabetic nephropathy (diabetic glomerulopathy) are less frequently observed in nonproteinuric diabetic kidney disease, although findings of interstitial and arterial features changed depending on the study [19][20][21].…”

Section: Pathology Of Nonproteinuric Diabetic Kidney Diseasementioning

confidence: 88%

“…Exploration of biomarkers apart from level of albuminuria may elucidate a mechanism of progression of nonproteinuric diabetic kidney disease. For example, an analysis of a nationwide biopsy-based cohort in Japan with a thorough glomerular investigation showed that diffuse lesions, polar vasculosis and subendothelial space widening predict the prognosis of advanced CKD even in the absence of proteinuria [21]. Notably, the subendothelial space widening also provides prognostic value on predicting CVD events in patients with nonproteinuria.…”

Section: Discussionmentioning

confidence: 99%

“…Proteinuric diabetic kidney disease develops proteinuria prior to renal function loss. eGFR estimated glomerular filtration rate, UACR urine albumin to creatinine ratio that diabetic kidney disease is not only clinically but also pathologically heterogeneous [18][19][20][21].…”

Section: Pathology Of Proteinuric Diabetic Kidney Diseasementioning

confidence: 99%

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Nonproteinuric diabetic kidney disease

et al. 2020

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Proteinuria has been considered to be the hallmark of diabetic kidney disease and to precede renal function loss. However, it has become clear that a substantial proportion of patients either with type 1 diabetes or type 2 diabetes have renal function loss without proteinuria, known as nonproteinuric diabetic kidney disease. Despite increasing recognition of the prevalence of nonproteinuric diabetic kidney disease, data on this phenotype of diabetic kidney disease is sparse. This review describes ever known clinical and pathological manifestations, renal prognosis, and mortality in patient with nonproteinuric diabetic kidney disease.

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Section: Pathology Of Nonproteinuric Diabetic Kidney Diseasementioning

confidence: 88%

Section: Discussionmentioning

confidence: 99%

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Nonproteinuric diabetic kidney disease

et al. 2020

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“…Mesangiolysis or double contours of basement membranes were also regarded as histologic findings of TMA in the kidney [22]. Because each histologic finding was also observed in various conditions, such as intraluminal microthrombi in disseminated intravascular coagulation [25], fibrinoid necrosis in various vasculitis [26], and mesangiolysis and double contours of the basement membranes in diabetic nephropathy [27], a combination of histologic findings was required for the diagnosis of TA-TMA. Sequential histologic findings, such as from endothelial cell separation through a widening of the subendothelial space to an intraluminal fibrin in the subendothelial space, directly reflect endothelial injury, and such findings are considered the characteristics of TMA.…”

Section: Autopsy Reviewmentioning

confidence: 99%

Distribution of Transplantation-Associated Thrombotic Microangiopathy (TA-TMA) and Comparison between Renal TA-TMA and Intestinal TA-TMA: Autopsy Study

Yamada

Nemoto

Ohashi

et al. 2020

Biology of Blood and Marrow Transplantation

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Transplantation-associated thrombotic microangiopathy (TA-TMA) is an important complication of hematopoietic stem cell transplantation. To date, information regarding the organs that are affected by TA-TMA as confirmed histologically remains limited; the clinicopathologic differences between renal TA-TMA and intestinal TA-TMA have not been examined despite being the well-known and commonly affected sites of TA-TMA. We therefore examined 165 autopsied patients after hematopoietic stem cell transplantation and compared the clinicopathologic factors of renal and intestinal TA-TMA. It was clear that 38 (23%) of our patients had TA-TMA. In the TA-TMA cases, the kidney (61%) and intestine (53%) were commonly affected, and the ileum and right colon were vulnerable. Other organs that we found to be affected by TA-TMA included the stomach (8%), gallbladder (5%), and oral cavity, pharynx, esophagus, liver, heart, urinary bladder, and ureter (all at 3%), and symptoms thought to be caused by TA-TMA of these organs were not observed in any patient. Histologically, TA-TMA only affected the arteriole, or small arteries, regardless of the organ, and the veins or larger arteries were not affected at all. In the kidney, the glomerular capillary was also affected, and mesangiolysis and double contours of the basement membranes were often in evidence. The histologic overlap of renal and intestinal TA-TMA was rare (13%), and the patients in the intestinal TA-TMA group exhibited more frequency of a history of intestinal acute graft-versus-host disease (GVHD) during the clinical course compared with that of the renal TA-TMA group (80% versus 22%, P = .0016). Although TA-TMA can affect many other organs, the frequency of these ancillary events was low, and the clinical effect may have been small. Our results suggest that in comparison to renal TA-TMA, intestinal GVHD could be more closely associated with intestinal TA-TMA as a risk factor.

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“…The severity of the diffuse lesions in the glomeruli was scored from 0 to 4 according to the description by Gellman et al (score 0, all glomeruli appear normal; score 1, local lesions present within each glomerulus and focal lesions present within the kidney; score 2, diffuse mesangial thickening within the glomerulus and generalized throughout the kidney; and score 3, narrowed capillary lumina and local obliteration) 3,12 . Nodular lesion, exudative lesion and mesangiolysis were defined as the presence or absence in each specimen 3,13 . The severity of interstitial fibrosis and tubular atrophy (IFTA) was scored from 0 to 3 according to the description by Tervaert et al (score 0, no IFTA; score 1, <25%; score 2, 25-50%; score 3, >50%) 2,3 .…”

Section: Pathological Examinationsmentioning

confidence: 99%

Association of renal arteriosclerosis and hypertension with renal and cardiovascular outcomes in Japanese type 2 diabetes patients with diabetic nephropathy

Shimizu

Furuichi

Toyama

et al. 2019

J of Diabetes Invest

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Aims/Introduction The present retrospective study investigated the impact of renal arteriosclerosis ( AS ) and hypertension ( HT ) on long‐term renal and cardiovascular outcomes in Japanese type 2 diabetes patients with biopsy‐proven diabetic nephropathy. Materials and Methods A total of 185 patients were enrolled. Patients were divided into four groups stratified by renal AS status and the presence of HT . The outcomes for this study were the first occurrence of renal events (a need for dialysis or a 30% decline in estimated glomerular filtration rate from baseline) and cardiovascular events (cardiovascular death, non‐fatal myocardial infarction, coronary intervention or non‐fatal stroke). Results The proportion of renal AS scores ≥1 was 88.3% among patients with normal‐range blood pressure ( BP ) and 95.4% among patients with HT. During a mean follow‐up period of 7.6 years, 129 episodes of renal composite events and 55 episodes of cardiovascular events were observed. Compared with patients with no renal AS and normal‐range BP , a renal AS score ≥1 increased the risk of renal composite events with a multivariable‐adjusted hazard ratio of 3.21 (95% confidence interval [95% CI] 1.27–8.14) in patients with normal‐range BP and 4.99 (95% CI 1.98–12.54) in patients with HT , whereas renal AS score ≥1 increased the risk of cardiovascular events with a multivariable‐adjusted hazard ratio of 6.06 (95% CI 1.24–29.61) in patients with normal‐range BP and 10.02 (95% CI 1.92–52.39) in patients with HT . Conclusions Renal AS was associated with increasing risks for renal composite events and cardiovascular events in both normal‐range BP and HT . The risks of renal composite events and cardiovascular events were the highest in both renal AS and HT .

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Nationwide multicentre kidney biopsy study of Japanese patients with type 2 diabetes

Abstract: This nationwide study on kidney biopsy of 600 cases with type 2 diabetes revealed that pathologic findings (presence of nodular lesions, exudative lesions and mesangiolysis) were strong predictors of kidney events in low-risk patients.

Cited by 67 publications

References 20 publications

Nonproteinuric diabetic kidney disease

Nonproteinuric diabetic kidney disease

Distribution of Transplantation-Associated Thrombotic Microangiopathy (TA-TMA) and Comparison between Renal TA-TMA and Intestinal TA-TMA: Autopsy Study

Association of renal arteriosclerosis and hypertension with renal and cardiovascular outcomes in Japanese type 2 diabetes patients with diabetic nephropathy

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