Diabetic kidney disease is a microvascular complication of diabetes mellitus and the leading cause of end-stage renal disease resulting in renal replacement therapy. Approximately 30% to 40% of diabetic patients have diabetic kidney disease, which contributes to a significant increase in morbidity and mortality. Microalbuminuria is considered the gold standard for diabetic kidney disease diagnosis; however, its predictive value is restricted. Although blood glucose control, blood pressure control, and angiotensin converting enzyme inhibitors have been the primary treatment strategies, there are no definitive treatment modalities capable of inhibiting the progression of kidney dysfunction in these patients. This study was undertaken to answer seven questions regarding the various aspects of diabetic kidney disease. Why does it develop? what kind of factors affect its development? How is it diagnosed? What are its possible biomarkers? When is a kidney biopsy necessary? What are the preventive and therapeutic options? And what are the novel treatments?
Angiotensin-Converting Enzyme Inhibitors ; Biomarkers ; Biopsy ; Blood Glucose ; Blood Pressure ; Diabetes Mellitus ; Diabetic Nephropathies ; Diagnosis ; Humans ; Kidney ; Kidney Failure, Chronic ; Mortality ; Renal Replacement Therapy

OBJECTIVES: Smoking is known to be associated with nephropathy in patients with diabetes. The distinct effects of smoking before and after diabetes has been diagnosed, however, are not well characterized. We evaluated the association of cigarette smoking before and after a diagnosis of diabetes with the presence of diabetic nephropathy. METHODS: We analyzed data from the 2011-2013 editions of the Korea National Health and Nutrition Examination Survey. A total of 629 male patients diagnosed with diabetes were classified as non-smokers (90 patients), former smokers (225 patients), or continuing smokers (314 patients). A "former smoker" was a patient who smoked only before receiving his diagnosis of diabetes. A "continuing smoker" was a patient who smoked at any time after his diabetes had been diagnosed. Diabetic nephropathy was defined as the presence of albuminuria (spot urine albumin/creatinine ratio ≥30 mg/g) or low estimated glomerular filtration rate (<60 mL/min/1.73 m2). Multiple logistic regression models were used to assess the independent association after adjusting for age, duration of diabetes, hemoglobin A1c, body mass index, systolic blood pressure, medication for hypertension, and medication for dyslipidemia. Female patients were excluded from the study due to the small proportion of females in the survey who smoked. RESULTS: Compared to non-smokers, continuing smokers had significantly higher odds ratio ([OR], 2.17; 95% confidence interval [CI], 1.23 to 3.83) of suffering from diabetic nephropathy. The corresponding OR (95% CI) for former smokers was 1.26 (0.70 to 2.29). CONCLUSIONS: Smoking after diagnosis of diabetes is significantly associated with the presence of diabetic nephropathy in the Korean male population.
Aged ; Albumins/analysis ; Asian Continental Ancestry Group ; Blood Pressure ; Body Mass Index ; Creatinine/urine ; Diabetes Mellitus, Type 2/complications/*diagnosis ; Diabetic Nephropathies/epidemiology/*etiology ; Female ; Glomerular Filtration Rate ; Hemoglobin A, Glycosylated/analysis ; Humans ; Logistic Models ; Male ; Middle Aged ; Nutrition Surveys ; Odds Ratio ; Prevalence ; Republic of Korea ; Smoking/*adverse effects

Diabetes is often associated with chronic kidney disease (CKD) and is the primary cause of kidney failure in half of patients who receive dialysis therapy. Given the increasing prevalence of diabetes and its high morbidity and mortality, diabetic nephropathy is a serious drawback in individual patients and a tremendous socioeconomic burden on society. Despite growing concern for the management of diabetic nephropathy, the prevalence of CKD with diabetes is the same today as it was 20 years ago. The current strategy to manage diabetic nephropathy, including the control of hyperglycemia, dyslipidemia, and blood pressure and the wide-spread use of renin-angiotensin-aldosterone system inhibitors, is well established to be beneficial in the early stages of diabetic nephropathy. However, the effects are uncertain in patients with relatively progressed CKD. Therefore, early diagnosis or risk verification is extremely important in order to reduce the individual and socioeconomic burdens associated with diabetic nephropathy by providing appropriate management to prevent the development and progression of this condition. This review focuses on recent research and guidelines regarding risk assessment, advances in medical treatment, and challenges of and future treatments for diabetic nephropathy.
Albuminuria ; Blood Pressure ; Diabetic Nephropathies* ; Dialysis ; Dyslipidemias ; Early Diagnosis* ; Glomerular Filtration Rate ; Humans ; Hyperglycemia ; Mortality ; Prevalence ; Renal Insufficiency ; Renal Insufficiency, Chronic ; Renin-Angiotensin System ; Risk Assessment

Diabetic nephropathy is the leading cause of end-stage renal disease, and is associated with increased risk of cardiovascular disease. Optimal control of blood glucose and blood pressure based on the blockade of renin-angiotensin system is the standard of care for the prevention and treatment of diabetic nephropathy. Regardless of these therapies, the prevalence of diabetic nephropathy continues to increase, highlighting the need for additional therapies. Diabetes affects the progression of kidney disease through a variety of mechanisms; several new therapeutic agents targeting these pathways have been developed, with currently being evaluated in clinical trials.
Albuminuria ; Blood Glucose ; Blood Pressure ; Cardiovascular Diseases ; Diabetic Nephropathies* ; Diagnosis ; Kidney Diseases ; Kidney Failure, Chronic ; Prevalence ; Renal Insufficiency, Chronic ; Renin-Angiotensin System ; Standard of Care

Spot urinary albumin to creatinine ratio (ACR) measurement has been suggested as a surrogate to 24-hr urine collection for the assessment of microalbuminuria, and cystatin C (cysC) is known as an advantageous marker for renal function. The aim of this study was to evaluate the clinical values of spot urinary ACR and serum cysC for the assessment of diabetic nephropathy instead of 24-hr urine microalbumin in children and adolescents with diabetes. A total of 113 children and adolescents (age 12-19 yr, M:F = 47:66) with type 1 or 2 diabetes were enrolled. We evaluated the validity of spot urine ACR and serum cysC, and then compared them to 24-hr urine microalbumin and creatinine clearance. Spot urine ACR was correlated with 24-hr urine albumin excretion (R2 = 0.828, P = 0.001) and creatinine clearance (R2 = 0.249, P = 0.017). The ROC curve analysis of serum cysC demonstrated higher diagnostic accuracy than that of serum creatinine (AUC 0.732 vs 0.615). Both the measurements of spot urine ACR and serum cysC might better predict the presence of diabetic nephropathy than 24-hr urine microalbumin in childhood diabetic patients.
Adolescent ; Albuminuria/*urine ; Child ; Creatinine/*urine ; Cystatin C/*blood ; Diabetes Mellitus, Type 1/*diagnosis ; Diabetes Mellitus, Type 2/*diagnosis ; Diabetic Nephropathies/*diagnosis ; Female ; Glomerular Filtration Rate ; Hemoglobin A, Glycosylated/analysis ; Humans ; Kidney Function Tests ; Male ; Predictive Value of Tests ; ROC Curve

BACKGROUND/AIMS: Many studies have demonstrated an association between hemoglobin levels and cardiovascular disease in diabetic patients. The aim of this study was to determine whether there is an association between hemoglobin concentrations and various clinical parameters, including metabolic factors, plasma C-peptide response after a meal tolerance test, and microvascular complications, in Korean patients with type 2 diabetes. METHODS: In total, 337 male patients with type 2 diabetes were recruited. All subjects were subjected to a meal tolerance test and underwent assessment of hemoglobin levels, fasting and postprandial beta-cell responsiveness, and microvascular complications. RESULTS: Patients with lower hemoglobin concentrations had a longer duration of diabetes, a lower body mass index, and lower concentrations of total cholesterol, triglycerides, and low-density lipoprotein cholesterol. They also had lower levels of postprandial C-peptide, Delta C-peptide, and postprandial beta-cell responsiveness. They had a higher prevalence of retinopathy and nephropathy. In multivariate analyses, there was a significant association between nephropathy and hemoglobin concentration. Also, hemoglobin concentrations were independently associated with Delta C-peptide levels and postprandial beta-cell responsiveness. CONCLUSIONS: Hemoglobin concentrations are associated with postprandial C-peptide responses and diabetic nephropathy in patients with type 2 diabetes.
Aged ; Biological Markers/blood ; Blood Glucose/metabolism ; C-Peptide/blood ; Cross-Sectional Studies ; Diabetes Mellitus, Type 2/*blood/diagnosis/epidemiology ; Diabetic Nephropathies/*blood/diagnosis/epidemiology ; Diabetic Retinopathy/*blood/diagnosis/epidemiology ; Hemoglobins/*metabolism ; Humans ; Insulin-Secreting Cells/metabolism ; Linear Models ; Lipids/blood ; Logistic Models ; Male ; Middle Aged ; Multivariate Analysis ; Odds Ratio ; Postprandial Period ; Prevalence ; Republic of Korea/epidemiology ; Risk Assessment ; Risk Factors

OBJECTIVETo investigate the relationship of Chinese medicine syndrome pattern with urinary albumin excretion rate (UAER) and its related factors in patients with diabetic nephropathy (DN).

METHODSSixty-three early stage DN patients were subjected to the study, the Chinese medicine syndrome patterns were differentiated, and their condition of methylene tetrahydrofolate reductase (MTHFR) C677T mutation was detected (shown by gene polymorphism of 677 base pairs). Meantime, plasma levels of homocysteine (Hcy), folic acid, fasting and postprandial glucose (FG and PG), glycohemoglobin (HbA1c), blood lipids as well as UAER were measured.

RESULTSSyndrome pattern was differentiated as yin-deficiency with heat-flourishing in 17 patients, qi-yin deficiency in 24, and yin-yang deficiency in 22; while accompanied blood stasis syndrome (BSS) was found in 35. Gene polymorphism detection indicated that 19 patients were of CC-type, 17 of TT-type, and 27 of CT-type. Analysis showed that higher UAER level often revealed in patients with BSS, as compared with that in patients of non-BS pattern, the difference was statistically significant (P < 0.05). UAER levels in patients of different genotypes were insignificantly different (P > 0.05), but showed a linear regressive relation, namely positively correlated with Hcy level in patients of isogeneic type (r = 0.674, P < 0.05). No statistical significance was found between levels of UAER and other related factors (P > 0.05).

CONCLUSIONUAER level in early stage DN patients of BSS pattern is rather higher, and it shows a linear regression relationship (positive correlation) with Hcy level in patients of isogeneic type.

Adult ; Aged ; Albuminuria ; physiopathology ; Diabetic Nephropathies ; genetics ; physiopathology ; urine ; Diagnosis, Differential ; Female ; Homocysteine ; blood ; Humans ; Male ; Medicine, Chinese Traditional ; Methylenetetrahydrofolate Reductase (NADPH2) ; genetics ; Middle Aged ; Polymorphism, Genetic

Idiopathic nodular glomerulosclerosis is an unusual entity with histopathologic features resembling nodular diabetic glomerulosclerosis but occurs in non diabetic patients and predominantly in older males with smoking and long standing hypertension. It is characterized histologically by nodular mesangial sclerosis, glomerular basement membrane thickening, and arteriolosclerosis in the absence of immune-type deposit, and clinical presentations typically include renal insufficiency and severe proteinuria with relatively poor prognosis. We experienced a rare case of idiopathic nodular glomerulosclerosis presenting rapid progressive renal failure in a 42-year-old man without clinical evidence of diabetes. He was admitted with peripheral edema and renal insufficiency. He had a history of hypertension for 2 years and chronic hepatitis B for 5 years. Funduscopy and renal ultrasound were normal. HbA1c and oral glucose tolerance test were normal and on serum and urine electrophoresis, M-spike was not found. Light microscopic examination demonstrated the characteristic features of lobular glomerulonephritis showing glomerular hypertrophy and nodular mesangial sclerosis. Immunofluorescence was negative for immune-type deposits. Electron microscopy showed marked increase of mesangial matrix, mesangial cell proliferation, moderate effacement of foot processes, and glomerular basement thickening without electron-dense deposits or other specific fibrils. Idiopathic nodular glomerulosclerosis was diagnosed. After discharge, he continued smoking and his blood pressure was not controlled. Three months after first biopsy, second biopsy was performed because of increasement of serum creatinine and specimens showed progression of tubulointerstitial change and nodular mesangial sclerosis. Subsequent serum creatinine was progressively increased and hemodialysis was started 13 months after diagnosis.
Adult ; Arteriolosclerosis ; Biopsy ; Blood Pressure ; Creatinine ; Diabetic Nephropathies* ; Diagnosis ; Edema ; Electrophoresis ; Fluorescent Antibody Technique ; Foot ; Glomerular Basement Membrane ; Glomerulonephritis ; Glucose Tolerance Test ; Hepatitis B, Chronic ; Humans ; Hypertension ; Hypertrophy ; Male ; Mesangial Cells ; Microscopy, Electron ; Prognosis ; Proteinuria ; Renal Dialysis ; Renal Insufficiency* ; Sclerosis ; Smoke ; Smoking ; Ultrasonography

BACKGROUND: Diabetic nephropathy is the main cause of the end-stage renal disease in Korea. This study was performed to evaluate the progression pattern and risk factors of diabetic nephropathy in type 1 diabetes patients. METHODS: Total 64 patients who were registered in Ajou University Hospital since April 1994 till April 2004 were enrolled. We retrospectively analyzed the influence of systolic and diastolic blood pressure, serum creatinine, total cholesterol, albumin, HbA1c and urine albumin excretion on the rate of decline in creatinine clearance (CCr) by Cockcroft- Gault equation. RESULTS: The patients (27 males/37 females), aged 32.8+/-9.1 (mean+/-SD) years, with a mean duration of diabetes of 9.5+/-4.9 years, were followed more than 6 months. CCr were 113.0+/-20 mL/min/1.73m2 at diagnosis and a mean decrease rate was 3.8+/-3.6 mL/ min/1.73m2/year. Doubling time of serum creatinine was 13.1+/-3.2 year in patients who developed doubling of their creatinine (26.6%). Microalbuminuria and overt proteinuria developed at 8.1+/-2.5 year and at 11.4+/-1.5 year after the diagnosis of type 1 diabetes respectively. A mean decrease rate of CCr was 6.1+/-2.9 mL/min/1.73m2/year in patients who develop ESRD after 14.2+/-2.8 years. During the follow up, systolic and diastolic blood pressure, serum total cholesterol were significantly higher and the mean serum albumin and creatinine clearance were significantly lower in chronic renal failure (CRF) group compared to non-renal failure (non-CRF) group (p< 0.05). There was no significant difference in HbA1c between CRF and non-CRF groups. CONCLUSION: The results may suggest that Korean type 1 diabetes patients with diabetic nephropathy in Ajou hospital have a rather faster decline in kidney function compared with other reports. But we need further prospective study to confirm this findings.
Blood Pressure ; Cholesterol ; Creatinine ; Diabetes Mellitus, Type 1 ; Diabetic Nephropathies* ; Diagnosis ; Follow-Up Studies ; Humans ; Kidney ; Kidney Failure, Chronic ; Korea* ; Proteinuria ; Retrospective Studies ; Risk Factors ; Serum Albumin

Patients with diabetes mellitus (DM) are associated with an increased risk of thrombosis, and are susceptible to a series of complications including nephropathy. It has also been known that plasma tissue factor (TF) antigen levels increase significantly in certain disease states. To investigate the clinical significance of an association with the various complications in patients with type 2 non-insulin-dependent DM (NIDDM), we measured the plasma levels of TF antigen in 63 patients (35 males and 28 females, mean age 60.8 yrs) with NIDDM and in 22 normal subjects (14 males and 8 females, mean age 56.0 yrs). The mean concentrations of TF were higher for patients with NIDDM (253.7 +/- 144.9 pg/ml) than in normal subjects (187.3 +/- 108.7 pg/ml with marginal statistical significance (p= 0.0530). The TF levels were higher for patients with a nephropathy than for patients without a nephropathy (p=0.0402). There was a significant positive correlation between levels of TF and BUN (r=0.84, p < 0.0001) or creatinine (r=0.93, p < 0.0001). However, TF levels were found to be similar for both groups with and without thrombosis, neuropathy, retinopathy, or infection. These results suggest that plasma TF antigen levels may be associated with nephropathy and they may reflect a renal dysfunction in NIDDM.
Biological Markers ; Diabetes Mellitus, Type II/*blood/*diagnosis ; Diabetic Nephropathies/blood/diagnosis ; Diabetic Retinopathy/blood/diagnosis ; Female ; Human ; Infection/blood/diagnosis ; Male ; Middle Aged ; Support, Non-U.S. Gov't ; Thromboplastin/*metabolism ; Thrombosis/blood/diagnosis