(B.Z., S.D.); the Departments of Medicine

New England Journal of Medicine, 2009

Background-Nephropathy and retinopathy remain important complications of type 1 diabetes. It is unclear whether early administration of drugs that block the renin-angiotensin system slows their progression.

Diabetologia, 2004

Aims/hypothesis. In a previous study conducted over the last decades we found a decreased incidence of nephropathy but unchanged incidence of severe retinopathy among patients with Type 1 diabetes diagnosed in childhood and with 20 years duration of diabetes. The aim of our current study was to investigate the incidence 5 to10 years later in the same population. Methods. We studied all 269 patients in whom Type 1 diabetes was diagnosed in childhood between 1961 and 1985 in a district in southeastern Sweden. Ninetyone percent were monitored for retinopathy until at least 1997 and 95% were monitored for nephropathy. Severe retinopathy was defined as laser-treated retinopathy and nephropathy as persistent proteinuria. Survival analysis was used and the patients divided into five cohorts according to the time of onset of diabetes. Results. The cumulative proportion of severe retinopathy had declined (p=0.006). After 25 years it was 47% (95% CI 34-61), 28% (15-40) and 24% (12-36) in the cohorts 1961 to 1965, 1966 to 1970 and 1971 to 1975 respectively. After 30 years it was 53% (40-66) and 44% (28-59) in the oldest cohorts. The cumulative proportion of nephropathy after 25 years duration was 30% (18-42), 8% (1-16) and 13% (4-23

Acta Diabetologica, 2011

We wanted to examine proliferative retinopathy as a marker of incident nephropathy in a 25-year follow-up study of a population-based cohort of Danish type 1 diabetic patients and to examine cross-sectional associations between nephropathy and retinopathy in long-term surviving patients of the same cohort. All type 1 diabetic patients from Fyn County, Denmark, were identified as of 1 July 1973. One hundred and eighty four patients were examined in 1981-1982 (baseline) and in 2007-2008 (follow-up). The level of retinopathy was graded by ophthalmoscopy at baseline and nine-field digital colour fundus photographs at follow-up. Single spot urine was used to evaluate nephropathy at both examinations. Proliferative retinopathy was present in 29 patients (15.8%) at baseline. At follow-up, these patients were more likely to macroalbuminuria (20.7% vs. 6.5%) than patients without proliferative retinopathy at baseline. In a multivariate logistic regression adjusted for baseline age, sex, duration of diabetes, smoking, HbA 1, systolic and diastolic blood pressure, odds ratio of nephropathy (micro-and macroalbuminuria combined) was 2.98 (95% confidence interval 1.18-7.51, p = 0.02) for patients with proliferative retinopathy at baseline as compared to those without. At follow-up, there was a close relation between retinopathy and nephropathy. The level of macroalbuminuria was 4.3, 4.6 and 13.0% for patients with no or mild non-proliferative retinopathy, moderate non-proliferative retinopathy and proliferative retinopathy, respectively. In conclusion, proliferative retinopathy is an independent marker of longterm nephropathy in type 1 diabetes. Upcoming studies should examine whether these microvascular complications are also causally linked in type 1 diabetes.

Diabetic nephropathy is the leading cause of kidney disease in patients starting renal replacement therapy and affects ϳ40% of type 1 and type 2 diabetic patients. It increases the risk of death, mainly from cardiovascular causes, and is defined by increased urinary albumin excretion (UAE) in the absence of other renal diseases. Diabetic nephropathy is categorized into stages: microalbuminuria (UAE Ͼ20 g/min and Յ199 g/min) and macroalbuminuria (UAE Ն200 g/min). Hyperglycemia, increased blood pressure levels, and genetic predisposition are the main risk factors for the development of diabetic nephropathy. Elevated serum lipids, smoking habits, and the amount and origin of dietary protein also seem to play a role as risk factors. Screening for microalbuminuria should be performed yearly, starting 5 years after diagnosis in type 1 diabetes or earlier in the presence of puberty or poor metabolic control. In patients with type 2 diabetes, screening should be performed at diagnosis and yearly thereafter. Patients with micro-and macroalbuminuria should undergo an evaluation regarding the presence of comorbid associations, especially retinopathy and macrovascular disease. Achieving the best metabolic control (A1c Ͻ7%), treating hypertension (Ͻ130/80 mmHg or Ͻ125/75 mmHg if proteinuria Ͼ1.0 g/24 h and increased serum creatinine), using drugs with blockade effect on the reninangiotensin-aldosterone system, and treating dyslipidemia (LDL cholesterol Ͻ100 mg/dl) are effective strategies for preventing the development of microalbuminuria, in delaying the progression to more advanced stages of nephropathy and in reducing cardiovascular mortality in patients with type 1 and type 2 diabetes. Abbreviations: ARB, angiotensin II type 1 receptor blocker; DCCT, Diabetes Control and Complications Trial; GFR, glomerular filtration rate; RAS, renin-angiotensin system; UAE, urinary albumin excretion; UKPDS, U.K. Prospective Diabetes Study.

Kidney International, 2015

c l i n i c a l i n v e s t i g a t i o n G Andrésdóttir et al.: Improved prognosis of diabetic nephropathy

Renal failure, 2018

The patients with Type 2 diabetes mellitus (T2DM) and diabetic retinopathy (DR) are prone to develop diabetic nephropathy (DN). In this study, we aimed to clarify the relationship between DR and the progression of DN in patients with T2DM. In the cross-section study, 250 patients with T2DM and biopsy-proven DN were divided into two groups: 130 in the DN without DR group (DN group) and 120 in the DN + DR group. Logistic regression analysis was performed to identify risk factors for DR. Of the above 250 patients, 141 were recruited in the cohort study who received follow-up for at least 1 year and the influence of DR on renal outcome was assessed using Cox regression. Renal outcome was defined as the progression to end-stage renal disease (ESRD). In the cross-section study, the severity of glomerular lesions (class IIb + III) and DM history >10 years were significantly associated with the odds of DR when adjusting for baseline proteinuria, hematuria, e-GFR, and interstitial inflamm...

Diabetes, 2003

Increased urinary albumin excretion rate is widely accepted as the first clinical sign of diabetic nephropathy. However, it is possible that some diabetic patients could first manifest reduced glomerular filtration rate (GFR) or hypertension. Relatively advanced diabetic renal lesions can be present in some diabetic patients with long-standing normoalbuminuria, and this might indicate increased risk of progression to microalbuminuria and then to overt diabetic nephropathy. The aim of this study was to identify a group of normoalbuminuric type 1 diabetic patients with low GFR and compare them with normoalbuminuric patients with normal GFR. Altogether, 105 normoalbuminuric type 1 diabetic patients with at least 10 years of diabetes duration that had a renal biopsy performed for research purposes were studied. Patients were divided according to GFR into groups with normal (>90 ml ⅐ min -1 ⅐ 1.73 m -2 ) or reduced (<90 ml ⅐ min -1 ⅐ 1.73 m -2 ) GFR. Clinical and renal structural parameters were compared between these two groups. Glomerular structural parameters were estimated by electron microscopic morphometry. The 23 patients with reduced GFR had more advanced diabetic glomerular lesions. The finding of reduced GFR was much more common among female patients, particularly if retinopathy and/or hypertension were also present. This report confirms that reduced GFR occurs among long-standing normoalbuminuric type 1 diabetic patients and is associated with more advanced diabetic glomerular lesions and, probably, with increased risk of progression. For these reasons, we suggest that regular measurements of GFR be performed in long-standing normoalbuminuric type 1 diabetic female diabetic patients, especially in those with retinopathy or hypertension. . AER, albumin excretion rate; GBM, glomerular basement membrane; GCRC, general clinical research center; GFR, glomerular filtration rate; HPLC, high-performance liquid chromatography; MC, mesangial cell; MM, mesangial matrix; Sv(PGBM/glom), surface density of the peripheral GBM per glomerulus; Vv(MC/glom), fractional volume of the glomerulus occupied by MC; Vv(Mes/glom), fractional volume of the glomerulus occupied by mesangium; Vv(MM/glom), fractional volume of the glomerulus occupied by MM.

Kidney Research and Clinical Practice, 2014

Diabetic nephropathy (DN) is a leading cause of mortality and morbidity in patients with diabetes. This complication reflects a complex pathophysiology, whereby various genetic and environmental factors determine susceptibility and progression to end-stage renal disease. DN should be considered in patients with type 1 diabetes for at least 10 years who have microalbuminuria and diabetic retinopathy, as well as in patients with type 1 or type 2 diabetes with macroalbuminuria in whom other causes for proteinuria are absent. DN may also present as a falling estimated glomerular filtration rate with albuminuria as a minor presenting feature, especially in patients taking renin-angiotensin-aldosterone system inhibitors (RAASi). The pathological characteristic features of disease are three major lesions: diffuse mesangial expansion, diffuse thickened glomerular basement membrane, and hyalinosis of arterioles. Functionally, however, the pathophysiology is reflected in dysfunction of the mesangium, the glomerular capillary wall, the tubulointerstitium, and the vasculature. For all diabetic patients, a comprehensive approach to management including glycemic and hypertensive control with RAASi combined with lipid control, dietary salt restriction, lowering of protein intake, increased physical activity, weight reduction, and smoking cessation can reduce the rate of progression of nephropathy and minimize the risk for cardiovascular events. This review focuses on the latest published data dealing with the mechanisms, diagnosis, and current treatment of DN.

Kidney International, 2004

Risk factors for renal replacement therapy in the Early Treatment Diabetic Retinopathy Study (ETDRS), Early Treatment Diabetic Retinopathy Study Report No. 26. Background. Diabetes is a leading cause of end-stage renal disease (ESRD). The purpose of this study is to assess the risk factors for renal replacement therapy (RRT) in the Early Treatment Diabetic Retinopathy Study (ETDRS). Methods. We examined demographic, clinical, and laboratory characteristics of the 2226 subjects with complete laboratory data enrolled in the ETDRS. The primary renal variable evaluated was the time to development of renal replacement therapy, defined as the need for dialysis or transplantation. Multivariable Cox proportional hazards regression was used to assess risk factors for type 1 and type 2 diabetes separately. Results. The 5-year estimated incidence of RRT in the entire ETDRS population was 10.2% and 9.8% for patients with type 1 and type 2 diabetes, respectively. Of those patients with complete data, 127 of 934 (14%) of patients with type 1 diabetes, and 150 of 1292 (12%) patients with type 2 diabetes required RRT during the study. Baseline risk factors common to type 1 and type 2 diabetes included elevated total cholesterol, and serum creatinine; and low serum albumin and anemia. Other risk factors significant in type 1 diabetes included body mass index (BMI), shorter duration of diabetes, elevated hemoglobin A 1c (HbA 1c), elevated systolic blood pressure, and the development of proliferative diabetic retinopathy. Risk factors significant in type 2 diabetes, but not type 1 diabetes, included younger age, proteinuria, and elevated triglycerides. Conclusion. In this study, major modifiable risk factors such as hypertension, dyslipidemia, and hyperglycemia were found

Asian Journal of Pharmaceutical and Clinical Research, 2017

Most overwhelming complications of Type 1 diabetes mellitus patients are responsible for complications related to the microvascular system most likely with kidney. In the kidney, hyperglycemia induced microangiopathy resulting not only thickening of the glomerular capillary basement membrane but also to the proliferation of the mesangial matrix and solidifying of the tubular basement membrane. Several biochemical and pathological, factors are concerned for the development of diabetic renal microangiopathy. These include the glomerular hyperperfusion and hyperfiltration, transformed morphology of podocytes accompanies these basement membrane modifications, Type IV collagen augmented synthesis following the hyperglycemia, and increased expression of tissue matrix metalloproteinase. The aim of this case review is to highlight the recent advances in understanding the pathogenesis, diagnosis, the overview and the potential renoprotective therapeutic agents that would prevent the development or the progression of diabetic nephropathy.