The Morphologic Patterns of Diabetic Nephropathy in Koreans

장시형,박문향 대한병리학회 2009 Journal of Pathology and Translational Medicine Vol.43 No.1

Background : Diabetic nephropathy is the most common cause of end-stage renal disease and it has various pathologic features. We investigated the clinicopathologic differences between the histologic classes of diabetic nephropathy. Methods : A total of 46 patients with diabetic nephropathy were evaluated. Morphologically, the renal lesions were divided into three categories: class 1, diffuse or nodular glomerulosclerosis: class 2, vascular change without evidence of glomerulosclerosis: and class 3, non-diabetic renal disease superimposed on diabetic glomerulosclerosis. We evaluated the laboratory findings and the histologic findings, including mesangial expansion, interstitial fibrosis and inflammation, arteriolar hyalinosis and tubular atrophy. Results : The proportion of each class was 32 cases (70%), 4 cases (9%) and 10 cases (21%), respectively. The clinical and laboratory data showed no significant difference among the classes. For the groups of class 1, the group with nodular sclerosis showed a higher serum creatinine level than did the diffuse group (p=0.003). IgA nephropathy was the most common nondiabetic renal disease superimposed on diabetic glomerulosclerosis in our study. Conclusions : The patients with nodular glomerulosclerosis presented with a more progressed clinicopathological features than did the patients with class 1 diffuse glomerulosclerosis. We also found 21% of all the patients with diabetic nephropathy had superimposed non-diabetic renal disease in a Korean population. Background : Diabetic nephropathy is the most common cause of end-stage renal disease and it has various pathologic features. We investigated the clinicopathologic differences between the histologic classes of diabetic nephropathy. Methods : A total of 46 patients with diabetic nephropathy were evaluated. Morphologically, the renal lesions were divided into three categories: class 1, diffuse or nodular glomerulosclerosis: class 2, vascular change without evidence of glomerulosclerosis: and class 3, non-diabetic renal disease superimposed on diabetic glomerulosclerosis. We evaluated the laboratory findings and the histologic findings, including mesangial expansion, interstitial fibrosis and inflammation, arteriolar hyalinosis and tubular atrophy. Results : The proportion of each class was 32 cases (70%), 4 cases (9%) and 10 cases (21%), respectively. The clinical and laboratory data showed no significant difference among the classes. For the groups of class 1, the group with nodular sclerosis showed a higher serum creatinine level than did the diffuse group (p=0.003). IgA nephropathy was the most common nondiabetic renal disease superimposed on diabetic glomerulosclerosis in our study. Conclusions : The patients with nodular glomerulosclerosis presented with a more progressed clinicopathological features than did the patients with class 1 diffuse glomerulosclerosis. We also found 21% of all the patients with diabetic nephropathy had superimposed non-diabetic renal disease in a Korean population.

Nondiabetic kidney diseases in type 2 diabetic patients

( Ye Jin Kim ),( Yoo Hyung Kim ),( Ki Dae Kim ),( Kang Ryun Moon ),( Jae Ho Park ),( Bo Mi Park ),( Hyewon Ryu ),( Dae Eun Choi ),( Ki Ryang Na ),( Kwang Sun Suh ),( Kang Wook Lee ),( Young Tai Shin ) 대한신장학회 2013 Kidney Research and Clinical Practice Vol.32 No.3

Background: The aim of this study was to evaluate the clinical characteristics of nondiabetic nephropathy in type 2 diabetes mellitus patients and to find a clinical significance of renal biopsy and immunosuppressive treatment in such a patient. Methods: Renal biopsy results, clinical parameters, and renal outcomes were analyzed in 75 diabetic patients who underwent kidney biopsy at Chungnam National University Hospital from January 1994 to December 2010. Results: The three most common reasons for renal biopsy were nephrotic range proteinuria (44%), proteinuria without diabetic retinopathy (20%), and unexplained decline in renal function (20.0%). Ten patients (13.3%) had only diabetic nephropathy (Group I); 11 patients (14.7%) had diabetic nephropathy with superimposed nondiabetic nephropathy (Group II); and 54 patients (72%) had only nondiabetic nephropathy (Group III). Membranous nephropathy (23.1%), IgA nephropathy (21.5%), and acute tubulointerstitial nephritis (15.4%) were the three most common nondiabetic nephropathies. Group III had shorter duration of diabetes and lesser diabetic retinopathy than Groups I and II (P¼0.008). Group II had the lowest baseline estimated glomerular filtration rate (P¼0.002), with the greatest proportion of renal deterioration during follow-up (median 38.0 months, Po0.0001). The patients who were treated with intensive method showed better renal outcomes (odds ratio 4.931; P¼0.01). Absence of diabetic retinopathy was associated with favorable renal outcome in intensive treatment group (odds ratio 0.114; P¼0.032). Conclusion: Renal biopsy should be recommended for type 2 diabetic patients with atypical nephropathy because a considerable number of these patients may have nondiabetic nephropathies. And intensive treatment including corticosteroid or immunosuppressants could be recommended for type 2 diabetic patients with nondiabetic nephropathy, especially if the patients do not have diabetic retinopathy.

Peroxisome Proliferators-Activated Receptor γ2 Pro12Ala 유전자 다형성과 당뇨병성 신증과의 연관성조사

이규호,정희석,최관용,김현,이달식,강지영,전현정,오태근 대한당뇨병학회 2008 Diabetes and Metabolism Journal Vol.32 No.5

Background: Peroxisome proliferators-activated receptor γ (PPARγ) is a member of the nuclear hormone receptor superfamily of ligand-activated transcription factors and known to play a role in regulating the expression of numerous genes involved in lipid metabolism, metabolic syndrome, inflammation, and atherosclerosis. The PPARγ2 Pro12Ala polymorphism has recently been shown to be associated with diabetic nephropathy. In this study, we evaluated the relationship between PPARγ2 Pro12Ala polymorphism and type 2 diabetic nephropathy whose duration of diabetes was over 10 years. Methods: We conducted a case-control study, which enrolled 367 patients with type 2 diabetes. Genotyping of PPARγ2 Pro12Ala polymorphism was performed using polymerase chain reaction followed by digestion with Hae III restriction enzyme. Results: The genotype or allele frequencies of PPARγ2 Pro12Ala polymorphism were not significantly different in diabetic patients with or without diabetic nephropathy. The genotype frequencies in terms of diabetic retinopathy and macrovascular complications such as coronary artery disease or stroke were not different either. Interestingly, nephropathy patients with Ala/Pro genotype showed lower C-peptide levels than those of Pro/Pro genotype. Conclusion: Our results suggest that PPARγ2 Pro12Ala polymorphism is not associated with diabetic nephropathy in type 2 diabetic patients. (KOREAN DIABETES J 32:402-408, 2008) Background: Peroxisome proliferators-activated receptor γ (PPARγ) is a member of the nuclear hormone receptor superfamily of ligand-activated transcription factors and known to play a role in regulating the expression of numerous genes involved in lipid metabolism, metabolic syndrome, inflammation, and atherosclerosis. The PPARγ2 Pro12Ala polymorphism has recently been shown to be associated with diabetic nephropathy. In this study, we evaluated the relationship between PPARγ2 Pro12Ala polymorphism and type 2 diabetic nephropathy whose duration of diabetes was over 10 years. Methods: We conducted a case-control study, which enrolled 367 patients with type 2 diabetes. Genotyping of PPARγ2 Pro12Ala polymorphism was performed using polymerase chain reaction followed by digestion with Hae III restriction enzyme. Results: The genotype or allele frequencies of PPARγ2 Pro12Ala polymorphism were not significantly different in diabetic patients with or without diabetic nephropathy. The genotype frequencies in terms of diabetic retinopathy and macrovascular complications such as coronary artery disease or stroke were not different either. Interestingly, nephropathy patients with Ala/Pro genotype showed lower C-peptide levels than those of Pro/Pro genotype. Conclusion: Our results suggest that PPARγ2 Pro12Ala polymorphism is not associated with diabetic nephropathy in type 2 diabetic patients. (KOREAN DIABETES J 32:402-408, 2008)

당뇨병성 신증환자에서 Malondialdehyde ( MDA ) 와 항산화효소의 변화에 관한 연구

박근용(Keun Yong Park) 대한내과학회 1997 대한내과학회지 Vol.53 No.5

Objective: Oxygen free radical activity is elevated in diabetes mellitus and has been implicated in the etiology of vascular complications and diabetic nephropathy is a serious microvascular complication in patients with IDDM. Despite intensive investigation, the pathophysiology of diabetic renal disease has not been fully elucidated. However, several clinical and experimental studies have suggested that endothelial dysfunction and changes of peritubular microcirculation. I performed this study to examine the oxidative stress in IDDM patients with diabetic nephropathy. Methods: Nine patients with IDDM (diabetic duration>5 years) and persistent albuminuria (albumin excretion>100㎎/day) and 15 normal healthy controls were investigated prospectively for MDA (thiobarbituric acid assay), and antioxidant enzymes [SOD (Hyland et al.), catalase (Nelson and Kiesow), GPX (Palgia and Valentine)]. Results: In RBC, levels of MDA were significantly higher in patients with diabetic nephropathy than in normal healthy controls and levels of antioxidant enzymes were significantly lower in patients with diabetic nephropathy than in normal healthy controls. In plasma, levels of MDA were significantly higher in patients with diabetic nephropathy than in normal healthy controls and levels of antioxidant enzymes except GPX were significantly lower in patients with diabetic nephropathy than in normal healthy controls. Conclusion: We conclude that increased oxidative stress and decreased antioxidative defense mechanism may be factors in the initiation of diabetic nephropathy.

Preventive effect of gymnema sylvestre homeopathic preparation on streptozotocin-nicotinamide induced diabetic nephropathy in rats

Lalit Kishore,Randhir Singh 경희대학교 융합한의과학연구소 2017 Oriental Pharmacy and Experimental Medicine Vol.17 No.3

Diabetic nephropathy is a long-term complication of diabetes mellitus. Chronic hyperglycemia leads to the generation of reactive oxygen species leading to oxidative stress. Hyperglycemia and oxidative stress are involved in the development of diabetic nephropathy. This study was designed to evaluate the effect of homeopathic preparation of Gymnema sylvestre Mother tincture, 6C and 30 C potencies on diabetic nephropathy in Wistar rats. Diabetic nephropathy was induced by intraperitoneal injection of streptozotocin (60 mg/kg) 15 min after Nicotinamide (230 mg/kg, i.p.) administration. Rats were divided into six groups (n = 6). Group 1 and 2 was kept normal control and diabetic control respectively whereas Groups 3–5 consist of diabetic nephropathy rats treated with different doses of G. sylvestre Mother tincture, 6C and 30 C potencies for 45 days. Glimepride (10 mg/kg) was used as standard. Diabetic nephropathy was assessed by determining serum glucose, urea, uric acid, creatinine level and tissue histological examination. Tissue antioxidant enzymes (SOD, GSH, LPO) level was measured to assess the oxidative stress. Also the level of advanced glycation end products in kidney was determined. Mother tincture, 6C and 30 C potencies of G. sylvestre produced significant attenuation in the biochemical parameters used to assess diabetic nephropathy. Moreover, oxidative stress and AGE’s level in kidney was also found to be significantly reduced. So, it can be concluded that Mother tincture, 6C and 30 C potencies of G. sylvestre have protective effect against diabetic nephropathy via inhibition of Oxidative stress and AGE’s.

스트렙토조토신 유발 당뇨병성 신증에서 Retinoid의 항 염증 효과

한상엽 ( Han Sang Yeob ),지이화 ( Ji I Hwa ),소경아 ( So Gyeong A ),한금현 ( Han Geum Hyeon ),강영선 ( Kang Yeong Seon ),차태룡 ( Cha Tae Lyong ),김형규 ( Kim Hyeong Gyu ),한지영 ( Han Ji Yeong ) 대한신장학회 2004 Kidney Research and Clinical Practice Vol.23 No.3

목적: 당뇨병성 신증의 원인 기전으로 염증반응이 관계한다고 알려진 이후 염증반응을 억제하고자 하는 시도가 있어왔다. 항염증 작용이 있는 retinoid는 면역성 신질환과 당뇨병에서 세포 외 기질 단백의 축적을 줄인다고 보고되었다. 그러나 retinoid가 당뇨병성 신증의 진행에 어떠한 역할을 하는지에 대해서는 연구가 미미한 상태이다. 이에 retinoid가 당뇨병성 신증의 진행과정에 관여하는 염증 작용을 차단할 수 있는지 규명하고자 하였다. 방법: Streptozotocin (STZ)을 쥐에 주사하여 당뇨를 유발시켜 염증 반응을 활성화한 뒤 retinoid를 투여하여 monocyte chemoattractant peptide-1 (MCP-1) 발현을 측정하여 항염증 효과를 평가하였다. 결과: 당뇨가 유발된 쥐들에서 군간 혈당 차이는 없었다. 당뇨 발생 초기 (2일)에 차이가 없던 24시간 요 단백양이 4주 후에는 증가되었고, 당뇨군 내에서는 retinoid를 투여한 군에서 투여하지 않은 군에 비해 단백뇨 양이 감소되는 경향을 보였다. 소변에서 발현된 MCP-1 단백양은 비당뇨군에 비해 당뇨군에서 초기부터 증가하는 경향을 보이다 4주 후에는 의미있게 증가하였다. 당뇨군에서 증가한 소변내 MCP-1 단백 발현이 retinoid를 투여한 경우 약 제를 투여하지 않은 군에 비해 감소하는 경향을 보였다. 신장 피질에서 추출한 RNA에서 MCP-1의 발현을 측정한 결과 비당뇨군에 비해 당뇨군에서 의미있게 증가되었으나 retinoid 투여효과는 관찰되지 않았다. MCP-1에 대한 면역 조직 화학 염색 결과 2일째부터 MCP-1 발현은 당뇨군에서 대조군에 비해 증가되어, 4주 후에는 의미 있게 차이가 났으며, retinoid를 투여한 경우 MCP-1의 발현은 뚜렷이 감소되었다. 결론: STZ 유발 당뇨쥐에서 MCP-1 단백 발현이 증가되는 것을 인하였고, 증가된 MCP-1 발현이 retinoid를 투여하는 경우 감소하는 것을 확인하였다. 이를 통해 당뇨병성 신증의 진행과정 중 retinoid가 염증반응을 차단할 수 있을 것으로 예상하였다. Background : An inflammatory mechanism has been suggested to contribute to the progression of diabetic nephropathy. Although retinoid, a known anti-inflammatory agent. has been reported to be beneficial in some experimental renal diseases, it has not been shown whether it prevents disease progression in diabetic nephrogathy. Therefore, we investigated whether all-trans retinoic acid inhibits inflammatory changes and improves renal function during the early stages of diabetic nephropathy in streptozotocin-induced diabetic rats. Methods : We evaluated anti-inflammatory effect of retinoid on streptozotocin-induced diabetic nephropathy. Anti-inflammatory effect was determined by the expression of monocyte chemoattractant peptide-1 (MCP-1). Results : Urinary protein excretion was significantly higher in diabetic rats at four weeks after the induction of diabetes mellitus compared with controls, and proteinuria in the group with retinoic acid treatment was decreased (1.25±0.69 vs. 0.78k0.72 mg/mg Cr, p=0.056). Urinary excretion of MCP-1 was rapidly increased at two days after induction of diabetes mellitus in diabetic rats, and further increased until four weeks of age compared with control rats. Retinoic acid treatment suppressed to 30% reduction of the urinary level of MCP-1 compared with vehicle treated diabetic rats (l19.3 ± 74.2 vs. 78.1±62.7 pg/mg Cr, p=0.078). Immunohistochemistry revealed a significant increase in staining for MCP -1 protein in the diabetic kidney, and retinoic acid treatment significantly suppressed intrarenal MCP-1 protein synthesis. Conclusion : Retinoic acid suppressed proteinuria and inflammatory changes in diabetic rats. These results suggest that retinoic acid may have an anti inflammatory effect in diabetic nephropathy. (Korean J Nephrol 2004;23(3):377-384)

당뇨병성 신증에 관한 연구

하종영(Chong Y . Ha),장현철(Hyun C . Jhang),최은영(Eun Y . Choi),박성광(Sung K . Park),백홍선(Hong S . Baek),강성귀(Sung K . Kang) 대한내과학회 1992 대한내과학회지 Vol.43 No.4

Background: About one-half of type 1 diabetics, develop renal failure in a mean of 20years. Before the advent of dialysis and transplantion, renal failure was the leading cause of death in patients with diabetes. Even now, renal failure remains a major cause of death in diabetic patients. Extensive efforts are therefore being made to prevent kidney damage in diabetic patients. A major goal of physician working in this area has been to understand the natural history of diabetic nephropathy. Methods: Among 722patients with diabetes mellitus (DM) who were admitted to the Chonbuk National University Hospital during the period of 5years from 1986 to 1990, 98patients with diabetic nephropathy that were able to follow up were studied clinically concerning incidence of diabetic nephropathy, and prevalence of hyperlipidemia, hypertension, and clinical course in insulin-dependent diabetes mellitus (IDDM) and noninsuli-dependent diabetes mellitus (NIDDM), respectively. Results: In 247cases of diabetic patient 59.5% was from 50 to 60years old. Among them IDDM was 29.2%, NIDDM was 70.9%, Diabetic nephropathy developed in 55.6% of patient with IDDM, 33.1% of patients with NIDDM, suggesting IDDM may be more frequent than NIDDM in the development of diabetic nephropathy, In distribution by age, 61.2% was in 50 to 60years. During from onset of DM to diabetic nephropathy was 16.5±9years in IDDM, 9.5±5years in NIDDM, Especially 35% of diabetic nephropathy was occurred from 16 to 20years in IDDM, 37.9% from 6 to 10years in NIDDM, respectively. Frequence of hypertension associated with diabetic nephropathy was in 75.0% IDDM and 81.0% in NIDDM, respectively, In laboratory finding values for plasma triglyceride, cholesterol and glucose showed no significant difference between IDDM and NIDDM. Frequence of diabetic retinopathy associated with diabetic nephropathy showed 74.2% in IDDM, and 51.4% in NIDDM, suggesting IDDM may be more frequent than that of NIDDM. Frequency of chronic renal failure after diabetic nephropathy was 26.4% in IDDM and 10.4% in NIDDM, suggesting IDDM may be twice as frequent as NIDDM. Mortality rate showed 38.5% in hemodialysis and 40% in continuous ambulatory peritoneal dialysis. Difference by dialysis method in the mortality rate was not significant. Overall mortiality rate showed 13.3%. Concloaion: These observation strongly indicate that diabetic nephropathy may be more frequent in IDDM and early diagnosis and treatment may be very important in IDDM.

Diabetic Nephropathy in Type 2 Diabetic Retinopathy Requiring Panretinal Photocoagulation

Minji Ha,Seung Yong Choi,Mirinae Kim,Jong Kyeong Na,Young-Hoon Park 대한안과학회 2019 Korean Journal of Ophthalmology Vol.33 No.1

Purpose: To investigate the risk factors of diabetic nephropathy in patients with diabetic retinopathy requiring panretinal photocoagulation (PRP) and the visual prognosis. Methods: A retrospective review of electronic medical records was conducted at Seoul St. Mary’s Hospital, comprising 103 patients with type 2 diabetes mellitus and diabetic retinopathy who underwent PRP from 1996 to 2005. Patients with type 1 diabetes mellitus, non-diabetic renal disease, non-diabetic retinal disease, visually significant ocular disease, high-risk proliferative diabetic retinopathy, and advanced diabetic retinopathy were excluded. The patients were divided into three groups: no nephropathy (group 1, n = 45), microalbuminuria (group 2, n = 16), and advanced nephropathy (group 3, n = 42). Duration of diagnosis of retinopathy and nephropathy, glycosylated hemoglobin, visual acuity, complications, and treatment history were investigated. Results: The mean glycosylated hemoglobin of group 3 (8.4 ± 1.2) was higher than that of group 1 (7.7 ± 1.0) or group 2 (7.7 ± 1.0) (p = 0.04). Mean interval from PRP to diagnosis of nephropathy was 8.8 ± 6.0 years in group 2 and 8.7 ± 4.9 years in group 3. The significant decrease in visual acuity in group 3 (28 eyes, 35.9%) was significantly higher than that in group 1 (15 eyes, 18.1%, p = 0.01) or group 2 (6 eyes, 20.7%, p = 0.03). Only vitreous hemorrhage showed a significantly higher incidence in groups 2 and 3 than in group 1 (p = 0.02). Multivariate regression analysis revealed that female sex and lower glycosylated hemoglobin were significantly associated with a protective effect on development of nephropathy. Conclusions: In the clinical setting, many patients with PRP-requiring diabetic retinopathy develop nephropathy an average of 8 to 9 years after PRP. Male sex and higher glycosylated hemoglobin could be risk factors of nephropathy.

특징점 선택방법과 SVM 학습법을 이용한 당뇨병 데이터에서의 당뇨병성 신장합병증의 예측

조백환,이종실,지영준,김광원,김인영,김선일,Cho, Baek-Hwan,Lee, Jong-Shill,Chee, Young-Joan,Kim, Kwang-Won,Kim, In-Young,Kim, Sun-I. 대한의용생체공학회 2007 의공학회지 Vol.28 No.3

Diabetes mellitus can cause devastating complications, which often result in disability and death, and diabetic nephropathy is a leading cause of death in people with diabetes. In this study, we tried to predict the onset of diabetic nephropathy from an irregular and unbalanced diabetic dataset. We collected clinical data from 292 patients with type 2 diabetes and performed preprocessing to extract 184 features to resolve the irregularity of the dataset. We compared several feature selection methods, such as ReliefF and sensitivity analysis, to remove redundant features and improve the classification performance. We also compared learning methods with support vector machine, such as equal cost learning and cost-sensitive learning to tackle the unbalanced problem in the dataset. The best classifier with the 39 selected features gave 0.969 of the area under the curve by receiver operation characteristics analysis, which represents that our method can predict diabetic nephropathy with high generalization performance from an irregular and unbalanced dataset, and physicians can benefit from it for predicting diabetic nephropathy.

Role of Nitric Oxide in the Pathogenesis of Diabetic Nephropathy in Streptozotocin - Induced Diabetic Rats

(Ki Chul Choi),(Seong Cheol Lee),(Soo Wan Kim),(Nam Ho Kim),(Jong Un Lee),(Young Joon Kang) 대한내과학회 1999 The Korean Journal of Internal Medicine Vol.14 No.1

N/A Objectives: Several reports suggest that enhanced generation or actions of nitric oxide (NO) have been implicated in the pathogenesis of glomerular hyperfiltration and hyperperfusion that occurs in early diabetes. However, the precise role of altered NO generation in the pathogenesis of diabetic nephropathy is unclear. The present study was aimed at investigating the role of nitric oxide in the pathogenesis of glomerular hyperfiltration and hyperperfusion in streptozotocin-induced diabetic rats. Methods : To evaluate the role of NO in diabetic hyperfiltration, we measured plasma and urine concentrations of NO2-/NO3-, stable metabolic products of NO and protein expressions of three isoforms of nitric oxide synthase (NOS) in streptozotocin-induced diabetic rats. We also investigated renal hemodynamic changes, such as glomerular filtration rate (GFR) and renal plasma flow (RPF), in responses to acute and chronic administration of NO synthesis inhibitor, nitro-L-arginine methyl ester (L-NAME), in diabetic and control rats. Results : Diabetic rats exhibited significantly elevated plasma and urinary NO2-/NO3- levels at 28 days after streptozotocin injection, and total excretion of NO2-/NO3- was approximately five-fold higher in diabetic rats than controls. Insulin and L-NAME treatment prevented the increases in plasma and urinary NO2-/NO3- concentrations in diabetic rats, respectively. The three isoforms of NOS (bNOS, iNOS, and ecNOS) were all increased in the renal cortex, whereas they remained unaltered in the renal medulla at day 28. GFR and RPF were significantly elevated in diabetic rats, and acute and chronic inhibition of NO synthesis by L-NAME attenuated the renal hemodynamic changes (increases in GFR and RPF) in diabetic rats, respectively. Conclusions : NO synthesis was increased due to enhanced NOS expression in diabetic rats, and chronic NO blockade attenuated renal hyperfiltration and hyperperfusion in diabetic rats. In addition, diabetic rats exhibited enhanced renal hemodynamic responses to acute NO inhibition and excreted increased urinary NO2-/NO3-. These results suggest that excessive NO production may contribute to renal hyperfiltration and hyperperfusion in early diabetes.