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Biomedical subjects

B Feldt-Rasmussen

Publications and source records attributed to B Feldt-Rasmussen.

At least 19 recordsLinked to original sources
PubMed2006

Stabilized incidence of diabetic patients referred for renal replacement therapy in Denmark.

Despite an improvement in diabetes care during the last 20 years, the number of diabetic patients starting renal replacement therapy (RRT) has continued to increase in the Western world. The aim was to study the incidence of patients starting RRT in Denmark from 1990 to 2004. Data were obtained from The Danish National Registry; Report on Dialysis and Transplantation, where all patients actively treated for end-stage renal disease have been registered since 1990. The incidence of end-stage renal disease increased until 2001. Thereafter the incidence stabilized on 130 per million people (pmp). The number of diabetic patients starting RRT increased steadily from: 52 (number of patients) in 1990, 113 in 1995, 150 in 2000, 168 in 2001, and 183 in 2002. However, during the years 2003 and 2004 this number was significantly reduced by 15% to 156 and 155, respectively. This was mainly due to a 22% reduction in the number of non-insulin- treated (type II) diabetic patients (number of patients): 98, 82, and 76 in 2002, 2003, and 2004, respectively. The mean age in the background population, the mean age in diabetic patients starting RRT and the incidence of type I and type II diabetes increased during the study period. The encouraging stabilization in the incidence of diabetic patients referred for RRT observed in Denmark could be the result of implementation of a multifactorial and more intensive renoprotective intervention in patients with diabetes and chronic progressive renal disease.

Adult↗
PubMed2006

Is there a need to optimize glycemic control in hemodialyzed diabetic patients?

The report of Williams et al. gives rise to at least two important questions regarding diabetic patients on maintenance hemodialysis: (1) Does glycemic control play a significant role? (2) Is HbA1c a reliable measure of glycemic control? These questions are discussed. It is recommended that you treat ESRD patients with diabetes according to guidelines given for patients without ESRD.

Blood Glucose↗
PubMed2005

Orosomucoid in urine is a powerful predictor of cardiovascular mortality in normoalbuminuric patients with type 2 diabetes at five years of follow-up.

AIMS/HYPOTHESIS: To study whether urinary orosomucoid excretion rate (UOER) predicts mortality in normoalbuminuric patients with diabetes at 5 years of follow-up, and to investigate the relationship between orosomucoid in serum and urine. METHODS: A cohort of 578 patients with diabetes (430 type 2, 148 type 1) was followed prospectively for an average of 5 years. UOER was measured in timed overnight urine samples. RESULTS: Eighty-two patients with type 2 diabetes and 17 patients with type 1 diabetes died. Among patients with type 2 diabetes, 251 (58%) had normoalbuminuria; increased UOER independently predicted cardiovascular mortality (OR 4.94, 95% CI 1.60-15.22; p<0.006) in those with normoalbuminuria and in the entire cohort of patients with type 2 diabetes (odds ratio 3.63, 95% CI 1.50-8.81; p<0.005). Patients with increased UOER had a higher all-cause mortality than those with normal UOER (log-rank test, p<0.001 for type 2 patients; p<0.04 for type 1 patients). In patients with type 1 diabetes, there were five cardiovascular deaths and no significant predictive value of UOER. Patients with increased UOER had a subclinical increase in serum orosomucoid. CONCLUSION/INTERPRETATION: Increased UOER was an independent, powerful predictor of cardiovascular mortality in normoalbuminuric patients with type 2 diabetes and in the entire cohort of patients with type 2 diabetes. There were indications of UOER as being a valuable marker in type 1 diabetes that showed differences in survival between patients with normal versus increased UOER. Serum orosomucoid was associated with UOER; UOER may be a marker of low-grade inflammation in patients with diabetes.

Biomarkers↗
PubMed2005

Impaired vascular function during short-term poor glycaemic control in Type 1 diabetic patients.

AIM: To study the effects of short-term poor glycaemic control on vascular function in Type 1 diabetic patients. METHODS: Ten Type 1 diabetic patients, with diabetes duration of less than 10 years and normal urinary albumin excretion and ophthalmoscopy, were studied. All patients were examined after 48 h of good vs. poor glycaemic control within a 3-week period. Blood glucose was measured seven times daily for 2 days before each examination. External ultrasound was used to measure the dilatory response of the brachial artery to post-ischaemic increased blood flow (endothelium-dependent dilation) and to nitroglycerin (endothelium-independent dilation). Plasma concentration of von Willebrand factor antigen, adhesion molecules, vascular endothelial growth factor, homocystein and cholesterol were also measured. RESULTS: The median blood glucose levels in the 48 h before the examinations were [median (range), good vs. poor control]: 6.3 (5.0-7.6) vs. 15.9 (11.3-17.8) (mmol/l). The flow-associated vasodilation (% of baseline) was reduced during poor control: 102.7 (94.7-110.8) vs. 104.0 (99.6-118.5) (P < 0.05) as were the nitroglycerin-induced dilation (% of baseline): 114.5 (103.3-127.9) vs. 120.2 (106.8-148.0) (P < 0.05). P-von Willebrand factor antigen was high during poor control (kIU/l): 1.14 (0.73-1.84) vs. 0.86 (0.72-1.39) (P < 0.05) and so was P-vascular endothelial growth factor (ng/l): 288 (133-773) vs. 254 (90-383) (P < 0.05). CONCLUSIONS: Short-term (48 h) hyperglycaemia in Type 1 diabetic patients may disturb vascular function, possibly mediated through smooth muscle cell dysfunction as well as endothelial dysfunction. We suggest that prolonged and repeated episodes of hyperglycaemia could possibly lead to permanent vascular dysfunction and thereby development and progression of vascular complications in diabetes.

Adult↗
PubMed2002

Orosomucoid in urine predicts cardiovascular and over-all mortality in patients with Type II diabetes.

AIMS/HYPOTHESIS: Urinary orosomucoid excretion rate is increased in a substantial proportion of patients with Type II (non-insulin-dependent) diabetes mellitus and normal urinary albumin excretion rate. The aim of this study was to determine whether increased urinary orosomucoid excretion rate is predictive of increased mortality in patients with Type II diabetes. METHODS: In a cohort study including 430 patients with Type II diabetes, baseline urinary samples were analysed for orosomucoid and albumin. Mean follow-up was 2.4 years. RESULTS: We found that 188 (44 %) patients had normal and 242 (56 %) patients had increased urinary orosomucoid excretion rates. During the study period 41 patients died; out of these 23 patients died of cardiovascular diseases. Odds ratio for all-cause mortality was 2.50 (95 % CI 1.00-6.22) and odds ratio for cardiovascular mortality was 9.81 (1.31-73.6) having increased urinary orosomucoid excretion rate at baseline (odds ratios adjusted for age, sex, duration of diabetes, cardiovascular diseases, weight, medication, HbA1 c, plasma creatinine and urinary albumin excretion rate). Urinary albumin excretion rate was an independent predictor of all-cause mortality when urinary orosomucoid excretion rate was not included in the analysis. Subgroup analysis revealed that 39 % of the patients with normal urinary albumin excretion rate (n = 251) had increased urinary orosomucoid excretion rates and that these patients had a higher cardiovascular mortality (p = 0.007) than patients with normal urinary albumin excretion rate and normal urinary orosomucoid excretion rates. CONCLUSION/INTERPRETATION: We found that urinary orosomucoid excretion rate predicted all-cause and cardiovascular mortality in patients with Type II diabetes independently from other risk factors.

Albuminuria↗
PubMed2002

Is low birth weight a risk factor for the development of diabetic nephropathy in patients with type 1 diabetes? A population-based case-control study.

OBJECTIVES: To investigate if low birth weight as a consequence of intrauterine malnutrition is a risk factor for the later development of diabetic nephropathy. DESIGN AND SUBJECTS: In a case-control set-up a group of type 1 diabetic subjects with diabetic nephropathy (n = 51) and a matched control group with normal kidney function (n = 51) were compared. Diabetic nephropathy and normal kidney function were defined as urinary albumin excretion rate above 200 microg min-1 and below 20 microg min-1, respectively. The birth weights were all obtained from the midwives' original records. SETTING: The patients were identified from a population-based study of chronic diabetic complications in the Funen County, Denmark. MAIN OUTCOMES: Birth weights according to the presence of diabetic nephropathy. RESULTS: The median (10-90 percentile) birth weights were 3,600 g (2,960-4,274) in the group with diabetic nephropathy and 3,600 g (2,880-4,220) in the group without nephropathy, P = 0.52. In the lower quartile of birth weights the median (10-90 percentile) birth weights were 3,000 g (2,780-3,200) in the group with nephropathy versus 2,850 g (2,250-3,175) in the group without nephropathy, P = 0.07. In the upper quartile the median (10-90 percentile) birth weights were 4,225 g (4,000-4,741) in the nephropathy group and 4,000 g in the group without nephropathy, P = 0.13. We found no significant correlation between birth weights and log urinary albumin excretion rate (r = 0.148, P = 0.14) and no difference in the number of patients with nephropathy in the lower versus upper quartiles of birth weights. CONCLUSION: We found no evidence of low birth weight as a risk factor for the development of diabetic nephropathy.

Adolescent↗
PubMed2001

Elevated urinary albumin excretion is associated with impaired arterial dilatory capacity in clinically healthy subjects.

BACKGROUND: Elevated urinary albumin excretion (UAE) predicts atherosclerotic cardiovascular disease. It is hypothesized that elevated UAE is associated with a generalized vascular dysfunction. This study tested this hypothesis for conduit arteries. METHODS AND RESULTS: Clinically healthy subjects were selected: 19 with UAE >90th percentile in the background population (6.6 microgram/min<UAE<150 microgram/min) and 41 with normoalbuminuria (UAE <6.6 microgram/min). External ultrasound was used to measure the dilatory response of the brachial artery to postischemic increased blood flow (endothelium-dependent, flow-associated dilation) and to nitroglycerin (endothelium-independent, nitroglycerin-induced dilation). Plasma concentrations of the endothelial markers nitrate/nitrite, thrombomodulin, and von Willebrand factor antigen were also measured. Both flow-associated and nitroglycerin-induced dilations were significantly impaired in subjects with elevated UAE as compared with normoalbuminuric control subjects: 102.0+/-1.0% (mean+/-SEM) versus 104.3+/-0.6% (P<0.05) and 120.1+/-1.5% versus 123.8+/-1.0% (P<0.05). No differences in the plasma concentrations of endothelial markers were found. Conclusions-Slightly elevated UAE is associated with impaired conduit arterial dilatory capacity in clinically healthy subjects, and this impairment may be explained by a reduced dilatory response to nitric oxide of both endogenous and exogenous origin. Impaired arterial dilatory capacity may contribute to the increased cardiovascular risk in subjects with elevated UAE.

Adult↗
PubMed2001

Pregnancy outcome in type 1 diabetic women with microalbuminuria.

OBJECTIVE: To determine the influence of microalbuminuria on pregnancy outcome in women with type 1 diabetes. RESEARCH DESIGN AND METHODS: This prospective cohort study took place at the Obstetric Clinic at National University Hospital, Copenhagen, from January 1996 to February 2000. All Caucasian women with type 1 diabetes, unselected from the eastern part of Denmark, with a living fetus before 17 weeks of gestation on admission were asked to participate. For women with more than one delivery in the study period, only the first pregnancy was included. Of the remaining 246 women, 240 (98%) entered the study. They were categorized according to their urinary albumin excretion (normal urinary albumin excretion, <30 mg/24 h; microalbuminuria, 30-300 mg/24 h; or diabetic nephropathy, >300 mg/24 h) before pregnancy or in the first trimester. RESULTS: A total of 203 women (85%) had normal urinary albumin excretion, 26 (11%) had microalbuminuria, and 11 (5%) had diabetic nephropathy. Mean HbA(1c) at 2-6 weeks was 7.5% (SD 1.1), 8.1 (0.9), and 8.8 (1.3) (P < 0.001), respectively. Of all deliveries in women with normal urinary albumin excretion, microalbuminuria, and diabetic nephropathy, 35, 62, and 91% (P < 0.001), respectively, were preterm, and 2, 4, and 45% (P < 0.001), respectively, were small-for-gestational-age infants. Preeclampsia developed in 6, 42, and 64% of the women (P < 0.001), respectively. Category of urinary albumin excretion (P < 0.01) and HbA(1c) at 2-6 weeks (P < 0.05) were independently associated with preterm delivery. CONCLUSIONS: The prevalence of preterm delivery is considerably increased in women with microalbuminuria, mainly caused by preeclampsia. Classification according to urinary albumin excretion and metabolic control around the time of conception are superior to the White classification in predicting preterm delivery in women with type 1 diabetes.

Adult↗
PubMed2000

Urinary albumin excretion and 24-hour blood pressure as predictors of pre-eclampsia in Type I diabetes.

AIMS/HYPOTHESIS: To evaluate the value of 24-h blood pressure monitoring compared to office blood pressure and urinary albumin excretion in predicting pre-eclampsia in Type I (insulin-dependent) diabetes mellitus. METHODS: The study included 136 consecutive pregnancies in Caucasian women with Type I diabetes before gestation without diabetic nephropathy, anamnestic hypertension or early abortion. Values of urinary albumin excretion and office blood pressure before pregnancy and the HbA1C value at the time of conception were obtained. Microalbuminuria was defined as urinary albumin excretion of 30-300 mg/24 h in two out of three consecutive urine samples. Single measurements of 24-h urinary albumin excretion, office blood pressure and HbA1C were done five 5 times during pregnancy. In a subgroup of 74 women 24-h blood pressure measurements were done at 10 and 28 weeks of gestation. Pre-eclampsia was defined as office blood pressure higher than 140/90 mmHg accompanied by proteinuria above 0.3 g/24 h later than 20 weeks of gestation. RESULTS: Urinary albumin excretion and systolic blood pressure were higher before and throughout pregnancy in 14 women developing pre-eclampsia compared with women remaining normotensive (p <0.001; p < 0.05, respectively). By logistic regression analysis the best predictor for pre-eclampsia was microalbuminuria before pregnancy (p < 0.05) with no additive predictive effect of 24-h blood pressure or office blood pressure measurement. The night:day ratio of blood pressure was similar in the two groups. CONCLUSION/INTERPRETATION: Microalbuminuria before pregnancy is the strongest predictor of pre-eclampsia in Type I diabetes. Measuring 24-h blood pressure early in pregnancy did not improve the ability to identify women at risk.

Adult↗
PubMed2000

Plasma concentrations of VCAM-1 and ICAM-1 are elevated in patients with Type 1 diabetes mellitus with microalbuminuria and overt nephropathy.

AIMS: Elevated urinary albumin excretion is associated with macrovascular atherosclerotic complications in Type 1 diabetes mellitus. Adhesion molecules mediate leucocyte adhesion to the endothelium early in the atherosclerotic process. The present study tests the hypothesis that microalbuminuria and diabetic nephropathy are associated with elevated plasma concentrations of soluble vascular adhesion molecule (sVCAM)-1, soluble intercellular adhesion molecule (sICAM)-1, and soluble E-selectin (sE-selectin) aiming to illustrate factors of potential pathogenetic relevance for the excess cardiovascular disease in diabetic patients with renal complications. METHODS: Soluble adhesion molecule concentrations were measured by enzyme-linked immunosorbent assays (ELISA) in healthy controls (n = 16) and in 59 Type 1 diabetic patients: group 1-patients with normoalbuminuria (n = 16); group 2-patients with microalbuminuria (n = 15); group 3-patients with macroalbuminuria and normal serum creatinine (n = 15), group 4-patients with macroalbuminuria and moderately elevated serum creatinine (n = 13). RESULTS: Plasma concentrations of sVCAM-1 and sICAM-1 were similar in healthy controls and normoalbuminuric Type 1 diabetic patients, but the concentrations were increased by the presence of microalbuminuria and overt nephropathy (P < 0.001 and P < 0.0001, ANOVA). Concentrations of sE-selectin did not differ between diabetic patients and controls. CONCLUSIONS: Plasma concentration of sICAM-1 is elevated in Type 1 diabetic patients with microalbuminuria and the concentrations of sICAM-1 as well as sVCAM-1 are elevated in patients with macroalbuminuria and normal s-creatinine. The elevated plasma concentrations of these soluble adhesion molecule concentrations in patients with renal complication can be of pathogenetic importance for the development of atherosclerosis and plasma soluble adhesion molecule concentrations may provide additional information on cardiovascular risk.

Adult↗
PubMed2000

Plasma concentrations of endothelial vasoactive substances in clinically healthy subjects. associations with urinary albumin excretion and ambulatory blood pressure.

Elevated urinary albumin excretion (UAE) is a predictor of cardiovascular disease, and one possible explanation is that elevated UAE reflects a generalized vascular dysfunction. The present study tests whether the plasma concentrations of the two main endothelial vasoactive substances (nitric oxide and endothelin-1 [ET-1]) are changed in clinically healthy subjects with elevated UAE (>6.6 microg/ min-the 90th percentile in the background population) and to test associations between these concentrations and systemic blood pressure. Twenty-seven subjects with elevated UAE were compared with 46 matched controls with normoalbuminuria. Plasma concentration of ET-1 was measured using an ELISA method and plasma concentration of nitrate/nitrite using a photometric method. Twenty-four-hour blood pressure was measured using a portable recorder (TM-2421). No significant differences in the concentrations of nitrate/nitrite and ET-1 were found between the groups, e.g. 21 (10-105) vs. 18 (11 -152) (p=0.33) and 0.98 (0.58 1.95) vs. 1.10 (0.54 -1.50) (p = 0.27), respectively. However, plasma nitrate/nitrite was significantly positively correlated to systolic and diastolic blood pressure in subjects with normoalbuminuria but not in subjects with elevated UAE. In contrast, plasma ET-1 concentration was significantly positively correlated to systolic blood pressure only in subjects with elevated UAE. In conclusion, elevated UAE is not associated with changed plasma concentrations of endothelial vasoactive substances in clinically healthy subjects. However, nitrate/nitrite is positively correlated to BP only in subjects with normoalbuminuria, and ET-1 is positively correlated to BP only in subjects with elevated UAE.

Aged↗
PubMed2000

Elevated urinary albumin excretion is not linked to the angiotensin I-converting enzyme gene polymorphism in clinically healthy subjects.

An elevated urinary albumin excretion (UAE) in non-diabetic subjects without renal or cardiovascular disease has been shown to be predictive of ischaemic heart disease. An insertion (I)/deletion (D) polymorphism in the angiotensin I-converting enzyme (ACE) gene has been identified and the D allele may be associated with cardiovascular disease. The aim of this study was to find a potential linkage between this polymorphism and elevated UAE. For studies of UAE and cardiovascular pathophysiology, a highly selected population sample has been identified comprising all clinically healthy subjects aged 40-65 years with elevated UAE in a dipstick negative urinary sample (n = 27) from The Copenhagen City Heart Study. Neither the ACE genotype distribution (p = 0.12) nor the D and I allele frequencies (p = 0.69) differed significantly between subjects with elevated UAE and a matched normoalbuminuric control group (n = 46). Elevated UAE in clinically healthy subjects is not linked to the ACE gene polymorphism.

Albuminuria↗
PubMed2000

Arterial hypertension, microalbuminuria, and risk of ischemic heart disease.

Albumin excretion in urine is positively correlated with the presence of ischemic heart disease and atherosclerotic risk factors. We studied prospectively whether a slight increase of urinary albumin excretion, ie, microalbuminuria, adds to the increased risk of ischemic heart disease among hypertensive subjects. In 1983 and 1984, blood pressure, urinary albumin/creatinine concentration ratio, plasma total and HDL cholesterol levels, body mass index, and smoking status were obtained in a population-based sample of 2085 subjects, aged 30 to 60 years, who were free from ischemic heart disease, diabetes mellitus, and renal or urinary tract disease. Untreated arterial hypertension or borderline hypertension was present in 204 subjects, who were followed until 1993 by the National Hospital and Death Certificate Registers with respect to development of ischemic heart disease. During 1978 person-years, 18 (9%) of the hypertensive subjects developed ischemic heart disease. Microalbuminuria, defined as a urinary albumin/creatinine ratio above the upper decile (1.07 mg/mmol), was the strongest predictor of ischemic heart disease, with an unadjusted relative risk of 4.2 (95% CI 1.5 to 11.9, P=0.006) and a relative risk of 3.5 (95% CI 1.0 to 12.1, P=0.05) when adjusted for all other atherosclerotic risk factors, including age and gender. In conclusion, microalbuminuria confers a 4-fold increased risk of ischemic heart disease among hypertensive or borderline hypertensive subjects. Urinary albumin excretion should be measured regularly in a hypertension clinic, and a rigorous control of blood pressure and of other atherosclerotic risk factors is recommended in hypertensive patients with microalbuminuria.

Adult↗
PubMed2000

Microalbuminuria, endothelial dysfunction and cardiovascular risk.

Microalbuminuria was originally considered to be an important new risk factor for diabetic nephropathy. More recently, it has been convincingly shown that microalbuminuria is also an independent risk factor for cardiovascular morbidity and mortality in Type 1 and Type 2 diabetic patients. Even in the non-diabetic background population, microalbuminuria is a risk factor for cardiovascular mortality. What is the link between increased loss of albumin in urine and cardiovascular disease and mortality? As microalbuminuria is apparently associated with increased universal vascular sieving of albumin in terms of the transcapillary escape rate of albumin (TER-alb), microalbuminuria may reflect this universal sieving. The pathophysiology of increased TER-alb is unknown, but could be caused by haemodynamics or damage to the functional properties of the vascular wall. A number of studies have provided evidence of endothelial dysfunction in patients with microalbuminuria, which may be the common link accounting for the associations mentioned above. In this context, a number of markers of endothelial cell dysfunction have been found to be increased in patients with microalbuminuria. In addition, a number of functional in vivo tests of endothelial dysfunction have been performed in Type 1 and Type 2 diabetic patients as well as in normal controls. Overall, these studies indicate the existence of a functional vascular dysfunction in Type 1 diabetic patients and normal controls with microalbuminuria, which may be related to dysfunction of endothelial cells.

Albuminuria↗
PubMed1999

Transperitoneal transport in diabetic and non-diabetic patients on peritoneal dialysis.

To investigate differences in the transport characteristics of the peritoneal membrane between diabetic and non-diabetic patients on chronic peritoneal dialysis, a study was conducted in 21 non-diabetic and 18 diabetic patients. Transperitoneal transport of small solutes was evaluated in terms of the mass transfer area coefficients (urea, creatinine and glucose), ultra-filtration sieving coefficients (urea and creatinine) and by peritoneal equilibration test results. The capacity of the peritoneal membrane to transport macromolecules was evaluated by albumin mass transfer rates and clearances of albumin. Transperitoneal water transport was evaluated by the ultra-filtration properties and the lymphatic flow rates. Finally, the whole-body capillary permeability was estimated by measuring the unidirectional flux of albumin across the capillary wall, i.e. the transcapillary escape rate of 125I-labelled human albumin. Despite a significantly increased transcapillary escape rate of albumin in the diabetic patients, no differences in peritoneal membrane characteristics could be demonstrated between diabetic and non-diabetic patients on peritoneal dialysis.

Adult↗
PubMed1999

Impaired autoregulation of the glomerular filtration rate in patients with nondiabetic nephropathies.

BACKGROUND: The ability of the kidney to maintain constancy of the glomerular filtration rate (GFR) over a wide range of renal perfusion pressures is termed autoregulation. Defective autoregulation of GFR has been demonstrated in diabetic nephropathy. Whether this is also the case in patients with nondiabetic nephropathies is not known. METHODS: We investigated the effect of acute lowering of blood pressure (BP) on GFR in 16 (8 males and 8 females) albuminuric subjects suffering from different nondiabetic nephropathies and in 14 (7 males and 7 females) controls matched with respect to sex, age, BP, and baseline GFR. The subjects received in random order an intravenous injection of either clonidine (150 to 225 microg) or saline (0.154 mmol/liter) within two weeks. We measured GFR ([51Cr]-EDTA), albuminuria (enzyme-linked immunosorbent assay; ELISA), and BP (Takeda TM-2420). RESULTS: Clonidine induced similar reductions in mean arterial BP 17 (2) versus 19 (2) mm Hg [mean (SE)] in patients with nephropathy and in controls, respectively. GFR diminished in average from 89 (6) to 82 (5) ml/min/1.73 m2 (P < 0.05), and albuminuria declined from a geometric mean of 1218 (antilog SE 1.3) microg/min to 925 (1.3) in the patients with nondiabetic nephropathies (P < 0.05), whereas these variables remained unchanged in the control group. The mean difference between changes in GFR (95% confidence interval) between the nondiabetic macroalbuminuric and control subjects was 6.1 (-0.03 to 12.21) ml/min/1.73 m2 (P = 0.051). CONCLUSION: Our study suggests that albuminuric patients with nondiabetic nephropathies frequently suffer from impaired autoregulation of GFR.

Adolescent↗