Quantitative characterization of glomerular fibrosis with magnetic resonance imaging: a feasibility study in a rat glomerulonephritis model.

Glomerular fibrosis occurs in the early stages of multiple renal diseases, including hypertensive and diabetic nephropathy. Conventional assessment of glomerular fibrosis relies on kidney biopsy, which is invasive and does not reflect physiological aspects such as blood perfusion. In this study, we sought to assess potential changes of cortical perfusion and microstructure at different degrees of glomerular fibrosis using magnetic resonance imaging (MRI). A rat model of glomerular fibrosis was induced by injecting anti-Thy-1 monoclonal antibody OX-7 to promote mesangial extracellular matrix proliferation. For six rats on day 5 and five rats on day 12 after the induction, we measured renal cortical perfusion and spin-spin relaxation time (T2) in a 3-Tesla MRI scanner. T2 reflects tissue microstructural changes. Glomerular fibrosis severity was evaluated by histological analysis and proteinuria. Four rats without fibrosis were included as controls. In the control rats, the periodic acid-Schiff (PAS)-positive area was 22 ± 1% of total glomerular tuft, which increased significantly to 56 ± 12% and 45 ± 10% in the day 5 and day 12 fibrotic groups, respectively ( P < 0.01). For the three groups (control, day 5, and day 12 after OX-7 injection), cortical perfusion was 7.27 ± 2.54, 3.78 ± 2.17, and 3.32 ± 2.62 ml·min-1·g-1, respectively, decreasing with fibrosis severity ( P < 0.01), and cortical T2 was 75.2 ± 4.6, 84.1 ± 3.0, and 87.9 ± 5.6 ms, respectively ( P < 0.01). In conclusion, extracellular matrix proliferation in glomerular mesangial cells severely diminished blood flow through the glomeruli and also altered cortical microstructure to increase cortical T2. The MRI-measured parameters are proven to be sensitive markers for characterizing glomerular fibrosis.

Imaging mass spectrometry reveals direct albumin fragmentation within the diabetic kidney.

Albumin degradation in the renal tubules is impaired in diabetic nephropathy such that levels of the resulting albumin fragments increase with the degree of renal injury. However, the mechanism of albumin degradation is unknown. In particular, fragmentation of the endogenous native albumin has not been demonstrated in the kidney and the enzymes that may contribute to fragmentation have not been identified. To explore this we utilized matrix-assisted laser desorption/ionization imaging mass spectrometry for molecular profiling of specific renal regions without disturbing distinct tissue morphology. Changes in protein expression were measured in kidney sections of eNOS-/-db/db mice, a model of diabetic nephropathy, by high spatial resolution imaging allowing molecular localizations at the level of single glomeruli and tubules. Significant increases were found in the relative abundances of several albumin fragments in the kidney of the mice with diabetic nephropathy compared with control nondiabetic mice. The relative abundance of fragments detected correlated positively with the degree of nephropathy. Furthermore, specific albumin fragments accumulating in the lumen of diabetic renal tubules were identified and predicted the enzymatic action of cathepsin D based on cleavage specificity and in vitro digestions. Importantly, this was demonstrated directly in the renal tissue with the endogenous nonlabeled murine albumin. Thus, our results provide molecular insights into the mechanism of albumin degradation in diabetic nephropathy.

Relationship between Renal Doppler Indices and Biochemical indices of Renal Function in Type 2 Diabetes Mellitus.

OBJECTIVES: Diabetic nephropathy is a common complication of diabetes mellitus due to microangiopathy leading to end stage renal disease. This study determined the relationship between renal resistivity index and pulsatility index with biochemical indices of renal function in patients with type 2 diabetes mellitus methods: This study involved 80 adults with type 2 diabetes mellitus. Urinary albumin excretion rate (UAER) and serum creatinine levels were measured, and the estimated glomerular filtration rate (eGFR) was calculated. Right renal resistivity index (RI) and pulsatility index (PI) values were determined. RESULTS: Mean renal resistivity index was 0.72±0.06 while the pulsatility index was 1.36 ± 0.24. Resistivity index was positively correlated with albuminuria (r = 0.426; p <0.001) and serum creatinine (r = 0.458; p <0.001), but negatively correlated with eGFR (r = -0.399; p <0.001). There was positive correlation between pulsatility index and albuminuria (r = 0.341; p = 0.002), and serum creatinine (r = 0.478; p = <0.001); and negative correlation between PI and eGFR (r = - 0.359; p = 0.001). CONCLUSIONS: Renal resistivity index and pulsatility index may provide valuable non-invasive estimate of predicting the presence and severity of renal dysfunction in patients with type 2 diabetes.

The evaluation of renal hemodynamics changes in Familial Mediterranean fever with color Doppler sonography.

BACKGROUND: Renal resistive index (RRI) scanned through renal Doppler is a practical marker employed in measuring blood flow in renal and intrarenal arteries and in noninvasive evaluation of renal vascular resistance. We aimed to investigate the renal hemodynamic variations in patients with Familial Mediterranean Fever (FMF). MATERIAL AND METHODS: Seventy-nine FMF patients and 51 healthy subjects suitable for age and sex were included. Patients were divided into two groups according to their urinary albumin excretion. Fifty-two patients with 0-29 mg/day albuminuria were included in the normoalbuminuric group while 27 patients with 30-299 mg/day albuminuria were included in the microalbuminuric group. RESULTS: RRI values were higher in patients with FMF compared to the healthy subjects (p < 0.0001). Additionally, RRI values were found to be higher in the microalbuminuric patients group compared to the normoalbuminuric patients group, and RRI values were also higher in normoalbuminuric patients group compared to the control group (p = 0.002, p < 0.0001). The ROC curve analysis suggested that the optimum RRI cutoff value for microalbuminuria in patients was 0.63, sensitivity of 66%, specificity of 60%, and p = 0.013. CONCLUSION: RRI may be a marker that may be used in assessing resistance to renal blood flow, early renal damage, and progression of renal damage in FMF patients.

Scoring System Development and Added Value of Albuminuria to Estimate Carotid Intima-media Thickness (CIMT) in Type 2 Diabetes Mellitus Patients.

AIM: to develop a scoring system and measure the diagnostic added value of albuminuria to estimate CIMT. METHODS: cross-sectional study was done in Endocrine Outpatient Clinic Cipto Mangunkusumo Hospital between March-May 2012 in T2DM patients without history of cerebrocardiovascular event, CKD stage ≥ III, and smoking. Bivariate analysis and multivariate (logistic regression) analysis was done, followed by developing the scoring system. RESULTS: from 71 subjects, there were 67.6% with increased CIMT and 73.3% with albuminuria. From 48 subjects with increased CIMT, 87.5% had albuminuria. Albuminuria measurement had high sensitivity (87.5%). Adding albuminuria measurement will increase the AUC as 2.3%. Estimation score for duration of DM, hypertension, dyslipidemia were as follows 1, 2, 1 respectively. Probability score of increased CIMT for score <2, 2, and >2 was as follows 15%, 57%, and 90%. CONCLUSION: albuminuria measurement increase the diagnostic value of CIMT. Scoring system can be used as a screening tool to estimate the increased of CIMT in type 2 DM patients without history of cerebrocardiovascular event, CKD stage ≥ III, and smoking.

Childhood kidney outcomes in relation to fetal blood flow and kidney size.

Impaired fetal abdominal blood flow may lead to smaller kidneys and subsequent impaired kidney function in later life. In a prospective cohort study among 923 pregnant women and their children, we measured fetal growth, kidney volumes, and umbilical and cerebral artery blood flow (median gestational age of 30.3 weeks; 95% range, 28.5-32.7 weeks). We used a higher umbilical/cerebral artery pulsatility index ratio as an indicator of preferential fetal blood flow to the upper body parts at the expense of the intra-abdominal organs. At a median age of 5.9 years (95% range, 5.7-6.6 years), we measured childhood kidney volumes, creatinine and cystatin C blood levels, microalbuminuria, BP, and eGFR. A preferential fetal blood flow to the upper body parts at the expense of the intra-abdominal organs associated only with a smaller combined kidney volume in childhood. Fetal combined kidney volume positively associated with childhood combined kidney volume and eGFR, and inversely associated with childhood creatinine and cystatin C levels (all P values <0.05), but did not associate with childhood microalbuminuria and BP. Children within the highest tertile of fetal umbilical/cerebral ratio and the lowest tertile of fetal combined kidney volume had the lowest eGFR (difference, -6.36 ml/min per 1.73 m(2); 95% confidence interval, -11.78 to -0.94 compared with children within the middle tertiles). These data suggest that impaired fetal blood to the abdominal organs and smaller fetal kidney size are associated with subclinical changes in kidney outcomes in school-aged children.

[INTERRELATIONS BETWEEN MICROALBUMINURIA AND RENAL FUNCTION WITH CONTRACTILE ABILITY OF LEFT VENTRICLE IN CARDIORENAL SYNDROME PATIENTS].

Chronic kidney disease (CKD) increases the risk of all-cause mortality and cardiovascular disease as well as progression to end stage kidney failure. The relationship of glomerular filtration rate (GFR) and albuminuria with clinical outcomes in the general population are revealed. This allows to present levels of GFR and microalbuminuria (MA), which increases the risk of mortality. Renal dysfunction, which revealed by the level of GFR and creatinine, can have definite role in hemodynamic changes and heart failure progression. For mentioning the interaction of cardiovascular and renal diseases the cardiorenal syndrome (CRS) term was introduced, with its classification on 5 types, according to the presence of acute/chronic heart failure and primary/secondary origination of heart and kidney injury. We study interrelations between echocardiographic data of left ventricular remodeling, MA level and degree of renal dysfunction in 115 patients with CRS. MA was measured with diagnostic strips, contractile function of left ventricle (LV) - by echocardiography and GFR was assessed by Cocroft-Gault method. The association between MA with decreased GFR and elevated creatinine levels and its connection with increased LV myocardial mass and preclinical disturbances of LV systolic function was revealed. We determined direct correlation between MA and myocardial mass index and indirect - between ejection fraction of LV and MA. Obtained data allow to mention the level of MA (25,4±5,8 ng/ml) in which there is more probability of LV contractile functional changes, which will allow early prediction and prevention of CRS progression and pathogenetically approved pharmacotherapy organization in this category patients.

Color Doppler sonographic dynamic tissue perfusion measurement demonstrates significantly reduced cortical perfusion in children with diabetes mellitus type 1 without microalbuminuria and apparently healthy kidneys.

MOTIVATION: With respect to the devastating consequences of the increasing prevalence of diabetes mellitus, the main reason for end stage renal disease and dialysis in industrialized countries, and the very limited diagnostic and therapeutic possibilities to predict, monitor and prevent diabetic nephropathy (DN), new concepts for early recognition and quantification of the prevailing microvascular changes in DN are urgently needed. MATERIALS AND METHODS: We present the first study of renal cortical tissue perfusion measurement by means of standardized color Doppler sonographic videos evaluated with the PixelFlux software 1 for Dynamic Tissue Perfusion Measurement (DTPM) in 92 patients with DM1 without MA compared to 71 healthy probands. RESULTS: DTPM reveals a highly significant diminution of cortical perfusion in patients with DM1 compared to healthy probands by 31 %, most pronounced in the distal hemicortex (reduction by 50 %) compared to 21 % within the proximal hemicortex. CONCLUSION: Thus, DTPM offers a novel means of numerically describing the state of the renal microvasculature in DM in a patient-friendly, non-invasive, non-ionizing manner.

Aortic wall thickness and amniotic fluid albuminuria in growth-restricted twin fetuses.

BACKGROUND AND OBJECTIVE: Intrauterine growth restriction (IUGR) may be associated with significantly higher aortic intima-media thickening (aIMT) values. It is unknown if fetal aIMT is associated with glomerulosclerosis and amniotic albuminuria in utero. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: Fetal abdominal aIMT and amniotic albumin/creatinine ratio (ACR) were measured in 126 individual twin fetuses, recruited by the Obstetrics and Gynaecology Clinics of the University of Padua (Italy) Medical Center. The IUGR twin fetuses were classified into two groups: Group A were those fetuses whose estimated fetal weight (EFW) was <10th percentile with pulsatility index >2 SD and Group B were those fetuses whose EFW was <10th percentile and had no velocimetry abnormalities. RESULTS: The median fetal aIMT was significantly different in the three groups (Group A = 0.9 mm; Group B = 0.7 mm; and appropriate for gestational age (AGA) = 0.5 mm; p < .0001). It was significantly higher in Group A than in the AGA group (p < .0001) and than in the Group B fetuses (p = .003), respectively. In addition, ACR was different in the three groups (Group A = 183,500 mg/g; Group B = 6,4720 mg/g; and AGA = 8,2750 mg/g; p = .0002). It was significantly higher in Group A than in the AGA group (p = .03) and than in Group B (p = .02), respectively. CONCLUSIONS: Growth-restricted twin fetuses with velocimetry abnormalities present are associated with aIMT and higher ACR levels in amniotic fluid, which could be possible markers in utero of preclinical atherosclerosis, and early glomerulosclerosis.

Albuminuria and carotid atherosclerosis as predictors of cognitive function in a general population.

BACKGROUND/AIMS: Albuminuria and carotid atherosclerosis are predictors of cardiovascular disease and potential predictors of cognitive decline. Our aim was to study whether albuminuria was an early predictor of cognitive function independent of carotid atherosclerosis in a general population. METHODS: The study population comprised 1,577 adults without self-reported stroke. In 1994 and 2007 all were screened for cardiovascular risk factors, urinary albumin-creatinine ratio (ACR), carotid intima-media thickness and carotid total plaque area (TPA). Endpoints were neuropsychological test results in 2007 from the digit symbol test, the finger-tapping test, the Mini Mental Status Examination and the 12-word test parts 1 and 2. Multivariate linear regression was used to assess associations. RESULTS: Higher ACR, ΔACR, intima-media thickness, TPA and ΔTPA independently predicted a lower score on the digit symbol test. Higher ΔACR and ΔTPA predicted a lower score on the finger-tapping test. Higher TPA predicted a lower score on the 12-word test part 1 (immediate recall). Smoking predicted lower scores on the digit symbol and finger-tapping tests independent of albuminuria and carotid atherosclerosis. CONCLUSIONS: Our results suggest that albuminuria, carotid atherosclerosis and smoking are independent predictors of executive function and motor tempo.

Relationship between microalbuminuria and vulnerable plaque components in patients with acute coronary syndrome and with diabetes mellitus. Virtual histology-intravascular ultrasound.

BACKGROUND: The purpose of the present study was to use virtual histology-intravascular ultrasound (VH-IVUS) to evaluate the relationship between microalbuminuria and plaque components in 920 patients. METHODS AND RESULTS: Patients with albumin levels <30mg/g creatinine were defined as having normoalbuminuria (n=824), and those with albumin levels 30-300mg/g as having microalbuminuria (n=96). The microalbuminuria group contained more patients with acute coronary syndrome (ACS; 72% vs. 61%, P=0.018) and more patients with diabetes (53% vs. 26%, P<0.001). In ACS patients, %necrotic core (NC) volume was significantly greater in the microalbuminuria group compared with the normoalbuminuria group (19±10% vs. 15±9%, P=0.019), but not in patients with stable angina. In ACS patients, thin-cap fibroatheroma (TCFA) was observed more frequently in the microalbuminuria group (36% vs. 18%, P=0.008), and microalbuminuria was the independent predictor of TCFA (odds ratio [OR], 1.106; 95% confidence interval [CI]: 1.025-1.144, P=0.018). In diabetic patients, %NC volume was significantly greater in the microalbuminuria group compared with the normoalbuminuria group (20±9% vs. 16±10%, P=0.017), but not in non-diabetic patients. In diabetic patients, TCFA was observed more frequently in the microalbuminuria group (38% vs. 17%, P=0.002) and microalbuminuria was the independent predictor of TCFA (OR, 1.120; 95%CI: 1.038-1.204, P=0.012). CONCLUSIONS: Microalbuminuria was associated with a higher number of vulnerable plaque components in ACS and diabetic patients. More intensive medical therapy is needed to stabilize the vulnerable plaque if microalbuminuria is observed in diabetic ACS patients.

Nocturnal blood pressure in untreated essential hypertensives.

AIM. Prevalence, correlates and reproducibility of nocturnal hypertension (NH) as defined by fixed cut-off limits in uncomplicated essential hypertension are poorly defined. Therefore, we assessed such issue in a cohort of 658 untreated hypertensives. METHODS. All subjects underwent procedures including cardiac and carotid ultrasonography, 24-h urine collection for microalbuminuria, ambulatory blood pressure monitoring (ABPM), over two 24-h periods within 4 weeks. NH was defined according to current guidelines (i.e. night-time blood pressure, BP ? 120/70 mmHg) and non-dipping status as a reduction in average systolic (SBP) and diastolic BP (DBP) at night lower than 10% compared with daytime values. RESULTS. A total of 477 subjects showed NH during the first and second ABPM period; 62 subjects had normal nocturnal BP (NN) in both ABPM sessions. Finally, 119 subjects changed their pattern from one ABPM session to the other. Overall, 72.5% of subjects had reproducible NH, 18% variable pattern (VP) and 9.5% reproducible NN. In the same group, figures of reproducible non-dipping, variable dipping and reproducible dipping pattern were 24%, 24% and 52%, respectively. Among NH patients, 56% of whom were dippers, subclinical cardiac organ damage was more pronounced than in their NN counterparts. CONCLUSIONS. In uncomplicated essential hypertensives, NH is a more frequent pattern than non-dipping; NH is associated with organ damage, independently of dipping/non-dipping status. This suggests that options aimed at restoring a blunted nocturnal BP fall may be insufficient to prevent cardiovascular complications unless night-time BP values are fully normalized.

Renal scintigraphy predicts global cardiovascular risk in hypertensive subjects with normal serum creatinine levels.

BACKGROUND. This cross-sectional study investigates the role of renal scintigraphy on cardiovascular (CV) risk stratification in normoalbuminuric, non-diabetic hypertensive subjects (HTs) free from CV disease and renal dysfunction. METHODS. In 200 HTs aged 55-75 years, glomerular filtration rate (GFR) was measured by technetium-99m-diethylene triamine pentacetic acid clearance during renal scintigraphy. Stage III chronic kidney disease (CKD) was defined as GFR < 60 ml/min/1.73 m(2). For comparing the impact of different methods for CKD diagnosis on CV risk stratification, CKD was also considered as GFR estimated by the Modification of Diet in Renal Disease (MDRD) equation and Cockcroft-Gault's formula. Target organ damage (TOD) was assessed by echocardiography and carotid ultrasonography. Gender-specific odds ratio (OR) with 95% confidence intervals for CKD were derived from a multiple stepwise logistic regression analysis. Global CV risk was stratified according to routine examinations, TOD and CKD. RESULTS. In 38% of cases, an unknown stage III CKD was found. Independent of age, CKD was predicted by history of hypertension (OR = 1.69, p = 0.0001), albuminuria (OR = 1.25, p = 0.0001), smoking (OR = 1.85, p = 0.028) and pulse pressure (OR = 1.21, p = 0.019) in men only. Men had an increased risk of CKD (OR = 2.62, p = 0.002) in comparison with women. Prevalence of TOD was significantly higher only in HTs having CKD diagnosed by renal scintigraphy; TOD and CKD assessment added to classic risk factors modified the CV risk stratification from low-moderate to high and very high. CONCLUSIONS. Renal scintigraphy is an important aid in risk stratification and should be performed in HTs aged >55 years. Pulse pressure was the main blood pressure component that predicted the risk of stage III CKD.

The estimated GFR, but not the stage of diabetic nephropathy graded by the urinary albumin excretion, is associated with the carotid intima-media thickness in patients with type 2 diabetes mellitus: a cross-sectional study.

BACKGROUND: To study the relationship between the intima-media thickness (IMT) of the carotid artery and the stage of chronic kidney disease (CKD) based on the estimated glomerular filtration rate (eGFR) and diabetic nephropathy graded by the urinary albumin excretion (UAE) in the patients with type 2 diabetes mellitus. METHODS: A cross-sectional study was performed in 338 patients with type 2 diabetes mellitus. The carotid IMT was measured using an ultrasonographic examination. RESULTS: The mean carotid IMT was 1.06 +/- 0.27 mm, and 42% of the subjects showed IMT thickening (>or= 1.1 mm). Cerebrovascular disease and coronary heart disease were frequent in the patients with IMT thickening. The carotid IMT elevated significantly with the stage progression of CKD (0.87 +/- 0.19 mm in stage 1, 1.02 +/- 0.26 mm in stage 2, 1.11 +/- 0.26 mm in stage 3, and 1.11 +/- 0.27 mm in stage 4+5). However, the IMT was not significantly different among the various stages of diabetic nephropathy. The IMT was significantly greater in the diabetic patients with hypertension compared to those without hypertension. The IMT positively correlated with the age, the duration of diabetes mellitus, and the brachial-ankle pulse wave velocities (baPWV), and negatively correlated with the eGFR. In a stepwise multivariate regression analysis, the eGFR and the baPWV were independently associated with the carotid IMT. CONCLUSIONS: Our study is the first report showing a relationship between the carotid IMT and the renal parameters including eGFR and the stages of diabetic nephropathy with a confirmed association between the IMT and diabetic macroangiopathy. Our study further confirms the importance of intensive examinations for the early detection of atherosclerosis and positive treatments for hypertension, dyslipidaemia, obesity, as well as hyperglycaemia are necessary when a reduced eGFR is found in diabetic patients.

Renal Doppler indices in diabetic children with insulin resistance syndrome.

End-stage renal failure is still a leading cause of mortality among type 1 diabetes patients. Insulin resistance plays a larger role in type 1 diabetes disease process than is commonly recognized. Detection of diabetic nephropathy as early as possible currently offers the best chance of delaying or possibly preventing progression to end-stage disease. Renal resistive index (RI) and pulsatility index (PI), measured using renal Doppler ultrasonography, reflect intrarenal vascular resistance. The present work aimed at examining renal Doppler indices (RI and PI) in type 1 diabetic children and their relation to features of insulin resistance and other established parameters of early diabetic nephropathy as microalbuminuria. One hundred diabetic children with a mean age of 13.4 ± 2.9 yr and an average diabetes duration of (7.2 ± 2.5 yr) were included. Thirty healthy children served as controls. All renal Doppler indices were significantly higher in children with type 1 diabetes mellitus (p ≤ 0.01). The worst parameters were observed in children diagnosed with insulin resistance syndrome (IRS) (38%), hypertensive (12%), and obese (4%) children. Resistive index showed a significant correlation to blood pressure (r = 0.2, p = 0.04), waist-hip ratio (r = 0.5, p = 0.02), insulin dose (r = 0.2, p = 0.02) and estimated glucose disposal rate (r = -0.5, p = 0.01). No correlation was noted to microalbuminuria, HbA1c, or duration of diabetes. The present work concluded that renal Doppler indices are worse in diabetic children and particularly those with IRS. These children appear to be at graver risk for diabetic nephropathy. In these patients adding renal Doppler assessment to their work up, might diagnose diabetic nephropathy at a prealbuminuric stage.

Similar renal outcomes in children with ADPKD diagnosed by screening or presenting with symptoms.

Autosomal dominant polycystic kidney disease (ADPKD) in children is sometimes considered to be a benign condition, with morbidity manifesting in adulthood. Therefore, diagnostic screening of children at risk is controversial. The aim of our study was to to compare the manifestations of ADPKD in children diagnosed by postnatal ultrasound (US) screening versus those presenting with symptoms. This was a retrospective chart review of children with ADPKD assessed in a single centre between 1987 and 2007. Age and reason for diagnosis were noted, and children were separated into two groups: (1) those diagnosed on the basis of family-based screening; (2) those presenting with a symptom. The two groups were compared for renal size, number of cysts, estimated glomerular filtration rate (eGFR), the presence of hypertension and microalbuminuria. In the 47 children with ADPKD (21 females) from 33 families who satisfied the enrollment criteria, mean (standard deviation) age at referral and last follow-up was 7.2 (4.4) and 12.9 (5.1) years, respectively, and the mean follow-up duration was 5.7 (3.6) years. Diagnosis was based on postnatal US screening in 31 children, whereas 16 were diagnosed after presenting with symptoms. The proportions of children with nephromegaly, hypertension, microalbuminuria and decreased eGFR, respectively, were similar in both groups. Based on these results, we conclude that renal-related morbidities, including hypertension and microalbuminia, do occur in children with ADPKD and at a similar frequency in those diagnosed after presenting with symptoms and those diagnosed upon postnatal screening. We suggest that at-risk children should have regular checks to detect hypertension. Moreover, affected children may benefit from novel therapies to minimise cystic disease progression.

Kidney function changes and their relation with the progression of cerebral small vessel disease and cognitive decline.

AIMS: We aimed to study whether worsening in markers of kidney function parallels the progression in cerebral small vessel disease (cSVD) and cognitive decline. METHODS: Data from the ISSYS (Investigating Silent Strokes in Hypertensives Study), a longitudinal population-based study in hypertensives aged 50-70 and dementia and stroke-free at baseline. At both visits, patients underwent a brain MRI, a cognitive diagnosis (normal aging or mild cognitive impairment, [MCI]) and urine and blood sampling collection. We assessed the incidence of infarcts and cerebral microbleeds, and the progression of white matter hyperintensities at periventricular (PVH) and deep areas. We determined changes in albumin-creatinine ratio and estimated glomerular filtration rate (eGFR). These changes were dichotomized into microalbuminuria at follow-up -either in subjects with or without baseline microalbuminuria- and significant decline in eGFR -lowest quintile of eGFR change (-10.57 mL/min/1.73m2)-. RESULTS: 360 patients were followed-up for 4 years. 80 (23%) patients presented microalbuminuria at follow-up and 68 (20.1%) experienced a significant eGFR decline. Considering cSVD change, we found a relationship between microalbuminuria at follow-up and progression in PVH (ß = 0.31, P-value = .01). Regarding cognitive decline, presence of microalbuminuria at follow-up related to a steeper decrease in memory function (ß = -0.36, P-value<.01). Moreover, patients with significant decline in eGFR were at higher risk of incident MCI (OR = 3.54, P-value = .02). These associations were independent of progression of cSVD. CONCLUSION: The worsening in markers of kidney function paralleled the decrease in cognition and the progression of cSVD, and this may be explained by common shared underlying risk factors.

Early Diabetic Nephropathy and Retinopathy in Patients with Type 1 Diabetes Mellitus Attending Sudan Childhood Diabetes Centre.

OBJECTIVE: Data on microvascular complications in children and adolescents with type 1 diabetes mellitus (T1DM) in Sudan are scarce. This study was aimed at determining the prevalence of diabetic nephropathy (DN) and retinopathy (DR) and their relationship to certain risk factors in children with T1DM attending the Sudan Childhood Diabetes Centre. Design and Methods. A clinic-based cross-sectional study of 100 patients with T1DM aged 10-18 years. Patients with disease duration exceeding 5 years if the onset of diabetes was prepubertal and 2 years if it was postpubertal were included. Relevant sociodemographic, clinical, and biochemical information was obtained. Blood pressure was measured. The patients were screened for DN and DR using urinary microalbumin estimation and fundus photography, respectively. RESULTS: The frequency of microalbuminuria and diabetic retinopathy was 36% and 33%, respectively. Eleven percent had both retinopathy and microalbuminuria. Seven percent of the patients were found to be hypertensive. Patients with diabetic retinopathy had significantly higher HbA1c levels (p = 0.009) and longer diabetes duration (p = 0.02) than patients without retinopathy. Logistic regression showed that high HbA1c (odds ratio (OR) 0.83, confidence interval (CI) 0.68-1.00, p = 0.04), but not age, duration, ethnic group, BMI, blood pressure, and presence of nephropathy, was an independent risk factor for retinopathy. Likewise, high blood pressure (OR 6.89, CI 1.17-40.52, p = 0.03), but not age, duration, ethnic group, BMI, HbA1c, and presence of retinopathy, was a predictor for nephropathy. CONCLUSION: High prevalence of incipient DN and early stages of DR were observed in this study. Longer diabetes duration and higher HbA1c were associated with the presence of diabetic retinopathy. High blood pressure was a risk factor for DN. So regular screening for these complications and optimization of glycemic control are needed.

Relation of albuminuria to left ventricular mass (from the HyperGEN Study).

Although albuminuria has been associated with a larger left ventricular (LV) mass in hypertensive and diabetic populations, little is known about this association in normotensive adults. We hypothesized that albuminuria is positively associated with LV mass in normotensive and hypertensive subjects. We analyzed data from 3,445 participants of the Hypertension Genetic Epidemiology Network (HyperGEN) Study (mean age 48.6 +/- 13.7 years, range 18 to 87, 57% women). LV parameters were obtained by echocardiography. Urinary albumin was estimated using standard methods. From the lowest to highest quartile of albuminuria, multivariable adjusted means of LV mass indexed to body surface area were 71.9, 73.3, 74.0, and 76.5 g/m2, respectively (p for trend = 0.002) in normotensive participants. Corresponding values for hypertensive subjects were 87.4, 89.3, 92.3, and 94.9 g/m2, respectively (p for trend <0.0001). Similar results were observed for LV mass indexed to height2.7. In secondary analyses, we found similar associations for men and women and after exclusion of subjects with diabetes. Furthermore, positive associations were observed between albuminuria and LV wall thickness in hypertensive and normotensive subjects. Albuminuria was negatively related to ejection fraction only in hypertensive subjects. In conclusion, these results suggest that albuminuria is positively associated with LV mass in normotensive subjects as it is in hypertensive subjects.

The relationship between microalbuminuria by using urine dipsticks and diabetic retinopathy in type 2 diabetes.

OBJECTIVE: Study the association between microalbuminuria and diabetic retinopathy in type 2 diabetic patients. MATERIAL AND METHOD: A cross-sectional analytic study of 1,111 cases with type 2 diabetic patients recruited from seven public hospitals, between June and December 2006 was performed RESULT: Two hundred eighty six subjects (79 males and 207 females) with urine dipsticks for microalbuminuria detection tested positive at least 2 of the 3 morning urine samples within 6 months. They were divided into 2 equal groups, micro- and normoalbuminuria based on quantity of albumin. Indirect ophthalmologic examination of all subjects' eyes for diabetic retinopathy was performed by ophthalmologists (retinal specialists). The present study showed that the proportion of diabetic retinopathy was 19.6% (28/143) and 12.6% (18/ 143) in micro- and normoalbuminuric groups, respectively. The difference of proportion between the groups was 7% but was statistically not significant (p = 0.108). CONCLUSION: Microalbuminuria detected using urine dipstick was not cross-sectionaly associated with diabetic retinopathy in type 2 diabetic patients.