Increased Urine Albumin Research Articles

Sodium Glucose Transport 2 (SGLT2) Inhibition Decreases Glomerular Hyperfiltration

Chronic kidney disease (CKD) is a growing major worldwide health problem 1. In the USA, about 14% of the population has CKD defined as an estimated glomerular filtration (eGFR) of 30 mg/g 1. Decreasing eGFR and/or increasing urine albumin level is associated with development of many comorbid conditions including highly significant increases in cardiovascular disease 2 and a significant increase in mortality rates as compared to age-matched controls without CKD3. A recent analysis led to the conclusion that possibly all of the excess mortality in people with type 2 diabetes as compared to the non-diabetic population is due to the development of CKD4. Perhaps the impact of CKD is best illustrated by the epidemic rise in the end stage renal disease (ESRD) population. In 1978, there were 41,421 people with ESRD (these numbers include all people on hemodialysis, on peritoneal dialysis, and who have received a transplant). In 2011, 612,966 people in the USA have ESRD, (an almost 15 fold increase in prevalence in 35 years) 1. Considering that death rates for people on dialysis are about 20% per year 1 and that there is a much better chance a CKD patient will die from cardiovascular disease than reach dialysis 5, there must be a very large number of people with CKD to produce the continued increase in prevalence in the ESRD population. There is also an enormous societal financial burden in that the cost of care for ESRD patients was near 30 billion dollars (about 6% of the Medicare budget for about 0.2% of the population). And as this dollar amount does not take into account care the CKD (pre-ESRD) population, the financial costs are actually much higher for the care of all people with kidney disease. In addition, this is an epidemic of global proportions. Indeed India and China have the most people with diabetes mellitus and will eventually have very high numbers of CKD patients.

Urinary albumin excretion as a marker of endothelial dysfunction in migraine sufferers: the HUNT study, Norway

ObjectiveTo investigate urine albumin leakage as a marker of endothelial dysfunction in migraine patients.DesignA population-based health study.Participants303 patients with migraine, 1009 patients with non-migraine headache and 5287 headache-free controls.OutcomesThe association...

Microalbuminuria: A Neglected Cardiovascular Risk Factor in Non-diabetic Individuals?

Microalbuminuria (MA), excessive albumin excretion in the urine, is defined in different ways. MA is more prevalent among patients with diabetes mellitus (DM) and/or hypertension and correlates with adverse renal and cardiovascular (CV) outcomes. Several cross-sectional and prospective studies have demonstrated a positive association between MA and CV outcomes in the general population but also specific populations such as patients with previous MI and hypertensives. The relationship between MA and hypertension is of particular importance. Increased urine albumin excretion (UAE) has been associated with left ventricular hypertrophy (LVH), subclinical markers of atherosclerosis and vascular dysfunction. Metabolic syndrome (MetS), insulin resistance (IR), inflammatory markers, lipid parameters and measures of obesity also correlate with increased UAE. Accumulating evidence suggests that a UAE value lower than the "traditionally" considered microalbuminuric threshold is associated with increased CV risk. The revision of MA definition according to the levels which confer increased CV risk in the general population should probably be considered. Further prospective studies with uniform methods of urine collection and UAE measurement as well as consistent threshold values and units may provide additional information regarding MA (or low-grade albuminuria) as a predictor of CV outcomes.

Albuminuria is associated with hip fracture risk in older adults: the cardiovascular health study

The microcirculation plays an important role in bone health. Here, we examine whether albuminuria, a marker of renal microvascular disease, is associated with the risk of hip fracture in older adults (age, 78years). We find a small independent association in women but not in men. The microvascular circulation plays an important role in bone physiology. Two studies of middle-aged adults have found that albuminuria (>30mg albumin/g creatinine), a disorder of the renal microvasculature, is associated with fracture risk. Here, we examine whether albuminuria is related to hip fracture risk and reduced hip bone mineral density (BMD) in older adults with a mean age of 78years. From the Cardiovascular Health Study (41% male), 3,110 adults with albuminuria testing were followed up for incident hip fracture for up to 9.5years. BMD was performed in a subset of 1,208 participants. There were 313 hip fractures during follow-up (7.7% of men; 11.7% of women). The incidence rate for men, with and without albuminuria, was 1.43 and 0.93/100 person-years of follow-up (p = 0.02); for women, 1.84 and 1.33 (p = 0.04). After adjustment for osteoporosis-related factors, frailty and falling, a doubling of albuminuria was significantly associated with hip fracture risk in women (hazard ratio, 1.12, 95% CI, 1.001-1.25), but not in men. In the subcohort with BMD measurement, increased urine albumin levels were significantly associated with decreased total hip BMD in men (-0.009g calcium/cm(2) (-0.017, -0.001); p = 0.04), but not in women. In older women, albuminuria is associated with a small, but statistically significant, increased risk of hip fracture independent of other explanatory factors. No such risk appears to be present in men, although their total hip BMD is lower in association with albuminuria.

Association of anemia and renal function test among diabetes mellitus patients attending Fenote Selam Hospital, West Gojam, Northwest Ethiopia: a cross sectional study

BackgroundAnemia is a common problem in diabetic patients. Diabetic patients have a greater severity of anemia as the level of Glomerular Filtration Rate (GFR) decreases compared to non-diabetic patients. Despite these facts, anemia is unrecognized and largely untreated in patients with diabetes in Ethiopia particularly in those patients attending Fenote Selam Hospital. Therefore, this study was aimed to assess the association of anemia and renal function test among diabetes mellitus patients attending Fenote Selam Hospital, North West of Ethiopia.MethodsAn Institutional -based cross-sectional study was conducted from February 2012 to April 2012 on diabetes mellitus (DM) patients. Systematic random sampling technique was used to get the total sample size of 384 patients. A total of seven ml of venous blood was collected from diabetes mellitus patients; two ml was collected by EDTA anticoagualted vacutainer test tube for haemoglobin determination and 5 ml venous blood was collected by plain vacutainer tube for creatinine and Blood urea nitrogen determination. The data were double entered and analyzed using SPSS-16 statistical software. The degree of association between independent and dependent variables was assessed using bivariate and multivariate logistic regression analysis in terms of P-value and odds ratio with 95% confidence interval.ResultsOut of the total 384 DM patients included in the study 73 (19%) were anemic. Fifty three (13.8%), forty eight (12.5%), and two hundred eighty three (73.7%) DM patients had an estimated GFR <60 ml/min/1.73 m, 60 – 90 ml/min/ 1.73 m, and > 90 ml/min/1.73 m respectively. One hundred eleven (28.9%) diabetic patients had increased urine albumin level. There was a statistically significant association between anaemia and Glomerular filtration rate (P<0.05) with Odds ratio of 8.58 and CI (10.21, 49.94). As the glomerular filtration rate increase, the risk to be anemic will decrease dramatically.ConclusionThe study showed that there was a significant association between anaemia and Glomerular filtration rate in DM patients. Therefore, DM patients should be strictly monitored for renal failure and anemia for proper management of diabetes patients.

Berberine ameliorates chronic kidney injury caused by atherosclerotic renovascular disease through the suppression of NFκB signaling pathway in rats.

Background and objectivesImpaired renal function in atherosclerotic renovascular disease (ARD) may be the result of crosstalk between atherosclerotic renovascular stenosis and amplified oxidative stress, inflammation and fibrosis. Berberine (BBR) regulates cholesterol metabolism and exerts antioxidant effects. Accordingly, we hypothesized that BBR treatment may ameliorate ARD-induced kidney injury through its cholesterol-lowering effect and also suppression of the pathways involved in oxidative stress, inflammation and NFκB activation.MethodsMale rats were subjected to unilateral renal artery stenosis with silver-irritant coil, and then fed with 12-week hypercholesterolemic diet. Rats with renal artery stenosis were randomly assigned to two groups (n = 6 each) – ARD, or ARD+BBR – according to diet alone or in combination with BBR. Similarly, age-matched rats underwent sham operation and were also fed with hypercholesterolemic diet alone or in combination with BBR as two corresponding controls. Single-kidney hemodynamic metrics were measured in vivo with Doppler ultrasound to determine renal artery flow. The metrics reflecting hyperlipidemia, oxidative stress, renal structure and function, inflammation and NFκB activation were measured, respectively.ResultsCompared with control rats, ARD rats had a significant increase in urinary albumin, plasma cholesterol, LDL and thiobarbituric acid reactive substances (TBARS) and a significant decrease in SOD activity. When exposed to 12-week BBR, ARD rats had significantly lower levels in blood pressure, LDL, urinary albumin, and TBARS. In addition, there were significantly lower expression levels of iNOS and TGF-β in the ARD+BBR group than in the ARD group, with attenuated NFκB-DNA binding activity and down-regulated protein levels of subunits p65 and p50 as well as IKKβ.ConclusionsWe conclude that BBR can improve hypercholesterolemia and redox status in the kidney, eventually ameliorating chronic renal injury in rats with ARD, and that BBR can act against proinflammatory and profibrotic responses through suppression of the NFκB signaling pathway.

Serum Fetuin-A Levels Related with Microalbuminuria in Diet-Induced Obese Rats

The aim of the study was to investigate the association between elevated serum fetuin-A and increased urine albumin excretion in obese rats, and whether increased urine albumin excretion was modified by improving hepatic steatosis and lipid metabolism disorder. Male Wistar rats 4 weeks in age were randomly divided into three groups and fed with normal chow (control group), high-fat chow (obesity group), or high-fat chow plus fenofibrate (fenofibrate group). After 24 weeks, both body weight and visceral fat/body weight ratio in obese rats were higher than in controls. A difference in serology markers and pathology associated with hepatic steatosis was also found among the three groups. Serum fetuin-A and the expression of NF-κB in the liver were increased, while serum adiponectin was decreased in obese rats in comparison to controls (P < 0.01). Urinary albumin/creatinine ratio (ACR) was increased in the obesity group compared to controls (P < 0.01). The fenofibrate intervention reduced serum fetuin-A and NF-κB expression in the liver and increased serum adiponectin compared to obese rats and was accompanied by decrease in ACR. A positive correlation was found between ACR and fetuin-A (r = 0.602, P < 0.01), and a negative correlation was found between ACR and adiponectin (r = −0.635, P < 0.01). We conclude that elevated fetuin-A levels are associated with microalbuminuria in obese rats, and abnormal albuminuria is reversible by improving hepatic steatosis.

Urinary albumin concentration and long-term cardiovascular risk in acute coronary syndrome patients: a PROVE IT-TIMI 22 substudy

Albuminuria has been shown to be associated with mortality and cardiovascular events, independent of traditional cardiovascular risk factors. This suggests that albuminuria may not just represent glomerular damage, but may be a marker of more diffuse endothelial dysfunction. We investigated the relationship between urinary albumin levels after an acute coronary syndrome and cardiovascular outcomes in statin treated subjects after acute coronary syndromes (ACS). Furthermore we assessed the effect of intensive statin treatment on albuminuria among patients in the PROVE IT-TIMI 22 trial, in which patients who had been hospitalized with ACS were randomized to pravastatin 40mg (standard therapy) or atorvastatin 80mg daily (intensive therapy). In univariate analyses, increasing urine albumin concentration was associated with increased risk of myocardial infarction, stroke, heart failure, and composite of death, myocardial infarction and stroke at 2 years. However, in a multivariable model containing traditional cardiovascular risk factors, albuminuria was not an independent predictor of the primary PROVE IT endpoint of death, myocardial infarction, unstable angina, revascularization and stroke, and was only an independent predictor of all-cause mortality at urinary albumin concentration >300mcg/ml. There was no significant change in urinary albumin concentration from enrolment to end of study in either the standard or intensive statin therapy groups, and no significant difference between treatment groups. Our results suggest that after an acute coronary syndrome in statin treated patients, microalbuminuria may reflect traditional cardiovascular risk factor burden and offer little prognostic information independent of those factors.

ROLE OF CHEMOKINE RECEPTOR 2 IN RENAL INJURY DURING DOCA-SALT HYPERTENSION

ObjectivesThis study was designed to determine the role of chemokine receptor 2 (CCR2), a receptor of MCP-1, in the development of salt-sensitive hypertension-induced renal damage.MethodsWe induced hypertension by uninephrectomy and...

Amlodipine Reduces Inflammation despite Promoting Albuminuria in the Streptozotocin-Induced Diabetic Rat

Amlodipine reduces blood pressure; however, its effect in the diabetic kidney irrespective of its blood pressure-lowering effects is unclear. This study examined the effects of amlodipine (0, 5, 10 and 20 mg/kg; D_A0, D_A5, D_A10 and D_A20, respectively) for 12 weeks on renal functional and structural changes in the streptozotocin-induced diabetic rat, a nonhypertensive model of diabetes-associated hyperfiltration. Compared with nondiabetic rats, diabetes (D) was associated with increased urine albumin excretion (UAE, 12.6 ± 3.40 vs. 3.73 ± 1.14 mg/day), glomerular filtration rate (2.17 ± 0.09 vs. 1.64 ± 0.12 ml/min/g kidney weight), glomerulosclerosis (0.21 ± 0.03 vs. 0.05 ± 0.01 AU) and infiltration of inflammatory cells (18.5 ± 2.78 vs. 6.92 ± 0.70 cells/cm²), but did not affect mean arterial pressure (MAP, 110 ± 4.70 vs. 109 ± 5.33 mm Hg). While D_A20 abolished glomerular hyperfiltration (1.49 ± 0.05 ml/min/g kidney weight) and inflammatory cell abundance (6.0 ± 0.79 cells/cm²), it exacerbated UAE (43.5 ± 8.49 mg/day) and increased MAP (132 ± 3.76 mm Hg), but had no effect on renal pathology. These data suggest that amlodipine reduces renal inflammation and abolished glomerular hyperfiltration, but increases blood pressure and exacerbates albuminuria in the rat model of normotensive diabetic kidney disease. We conclude that amlodipine may have limited renoprotective effects in the face of hyperfiltration and absence of elevated blood pressure.

Multiple injections of anti-mouse β2glycoprotein 1 antibody induce FcRγ-dependent fetal growth restriction (FGR) in mice

ObjectivesThe antiphospholipid syndrome (APS) is characterized by the presence of circulating antiphospholipid antibodies (aPLs), is a leading cause for thromboembolic events, repeated miscarriage, fetal loss and is a major risk factor for fetal growth restriction (FGR) and preeclampsia. In human, anti-β2 glycoprotein I (aβ2GPI) antibody is one of the aPLs and considered to be a specific and important marker for APS. However, pathophysiological changes induced by aβ2GPI antibodies in FGR are largely unknown. MethodsIn the present study, we developed a murine FGR model induced by multiple injections of WBCAL-1, a well-characterized mouse aβ2GPI monoclonal antibody. ResultsAdministration of WBCAL-1, but not the isotype control antibody and saline, into pregnant mice specifically decreased the size of fetuses and placentas without affecting the number of delivered pups. Also, a significant increase in urinary albumin and electron microscopic changes, such as splitting layers of basal membranes in the placental labyrinth and rearrangement of pores in glomerular endothelial cells, were observed in WBCAL-1 treated mice. WBCAL-1 injection did not induce any changes in blood pressure and typical parameters of blood thromboembolic symptoms. Furthermore, FcRγ deficiency protected the fetuses from aβ2GPI antibody-induced injuries. ConclusionsOur present findings suggest that proteinuria is a symptom associated with APS-related FGR with placental and renal tissue injuries, and that FcRγ might be a molecular target for prevention of aβ2GPI antibody-mediated obstetrical pathologies.

Inhibition of Advanced Glycation End Product Formation by Pu-erh Tea Ameliorates Progression of Experimental Diabetic Nephropathy

Accumulation of advanced glycation end products (AGEs) has been implicated in the development of diabetic nephropathy. We investigated the effects of Pu-erh tea on AGE accumulation associated with diabetic nephropathy. Although it did not affect blood glucose levels and insulin sensitivy, Pu-erh tea treatment for 8 weeks attenuated the increases in urinary albumin, serum creatinine, and mesangial matrix in db/db mice. We found that Pu-erh tea prevented diabetes-induced accumulation of AGEs and led to a decreased level of receptor for AGE expression in glomeruli. Both production and clearance of carbonyl compounds, the main precursor of AGE formation, were probably attenuated by Pu-erh tea in vivo independent of glyoxalase I expression. In vitro, HPLC assay demonstrated Pu-erh tea could trap methylglyoxal in a dose-dependent manner. Our study raises the possibility that inhibition of AGE formation by carbonyl trapping is a promising approach to prevent or arrest the progression of diabetic complications.

Relation of Impaired Coronary Microcirculation to Increased Urine Albumin Excretion in Patients With Systemic Hypertension and No Epicardial Coronary Arterial Narrowing

Coronary flow reserve (CFR) is impaired and urinary albumin excretion is increased in patients with essential hypertension. Our aim was to investigate the associations between CFR and cardiac and renal damage in hypertensives. For this purpose we studied 37 never-treated hypertensives (57.9 years old, 16 men) without chest pain but with a positive ischemia stress test result and normal coronary arteries on coronary angiogram. CFR was calculated by a 0.014-inch Doppler guidewire (Flowire, Volcano, San Diego) in the left anterior descending artery in response to bolus intracoronary administration of adenosine (60 μg) as the ratio of hyperemic to basal average peak velocity of the distal vessel. All participants underwent complete echocardiographic study including left ventricular diastolic function evaluation by tissue Doppler imaging (peak early diastolic velocity/peak atrial systolic velocity) and determination of the albumin-to-creatinine ratio (ACR). Hypertensives with low CFR (<2.5, n = 22) compared to those with high CFR (n = 15) exhibited a larger left ventricular mass index by 10.9 g/m(2) (p = 0.045) and ACR values by 10 mg/g (p <0.001). CFR was negatively correlated with logACR (r = -0.511, p = 0.001). LogACR (beta -0.792, p <0.001), male gender (beta 0.313, p = 0.005), left ventricular mass index (beta -0.329, p = 0.007), and peak early diastolic velocity/peak atrial systolic velocity (beta 0.443, p <0.001) were the only independent predictors of CFR in linear regression analysis (adjusted R(2) = 0.672). In conclusion, never-treated asymptomatic hypertensives who exhibit impaired CFR and angiographically normal epicardial arteries are characterized by intrarenal vascular damage as reflected by increased ACR. These findings suggest a plausible role of ACR estimation in the identification of hypertensive subjects with early coronary microvascular dysfunction.

Exposure to maternal overnutrition and a high-fat diet during early postnatal development increases susceptibility to renal and metabolic injury later in life.

Overnutrition during pre- and postnatal development both confer increased susceptibility to renal and metabolic risks later in life; however, whether they have an additive effect on the severity of renal and metabolic injury remains unknown. The present study tested the hypothesis that a combination of a pre- and postnatal diet high in fat/fructose would exacerbate renal and metabolic injury in male offspring later in life. Male offspring born to high fat/high-fructose-fed mothers and fed a high-fat/high-fructose diet postnatally (HF-HF) had increased urine albumin excretion (450%), glomerulosclerosis (190%), and tubulointerstitial fibrosis (101%) compared with offspring born to mothers fed a standard diet and fed a standard diet postnatally (NF-NF). No changes in blood pressure or glomerular filtration were observed between any of the treatment groups. The HF-HF offspring weighed ∼23% more than offspring born to mothers fed a high-fat/high-fructose diet and fed a normal diet postnatally (HF-NF), as well as offspring born to mothers fed a standard diet regardless of their postnatal diet. The HF-HF rats also had increased (and more variable) blood glucose levels over 12 wk of being fed a high-fat/high-fructose diet. A combination of exposure to a high-fat/high-fructose diet in utero and postnatally increased plasma insulin levels by 140% compared with NF-NF offspring. Our data suggest that the combined exposure to overnutrition during fetal development and early postnatal development potentiate the susceptibility to renal and metabolic disturbances later in life.

Association between an increment of 30-minute postchallenge plasma glucose and urine albumin excretion exists in postmenopausal women but not in premenopausal women

Usually, the increment of 30-minute postchallenge plasma glucose (ΔG30-0) represents the highest glucose spike in the population with normal glucose regulation (NGR). The aim of this study was to explore the differences in ΔG30-0 and urinary albumin excretion, a marker for widespread vascular damage, between premenopausal and postmenopausal women, and the relationship between ΔG30-0 and urinary albumin excretion. A population-based cross-sectional study, consisting of 5,289 participants aged 20 to 75 years from six different communities, was conducted in Shanghai between 2007 and 2008. We assessed postchallenge blood glucose and insulin at 0-, 30-, and 120-minute urinary albumin and creatinine. ΔG30-0 was calculated as 30-minute postchallenge glucose minus fasting plasma glucose, and the albumin-to-creatinine ratio (ACR) was used to reflect urinary albumin excretion. Among these, the data of 2,240 women with NGR were analyzed. (1) Postmenopausal women had higher ΔG30-0 and ACR than did premenopausal women (3.55 ± 1.52 mmol/L vs 3.21 ± 1.49 mmol/L and 6.92 [4.91-10.99] mg/g vs 6.18 [4.17-10.07] mg/g, respectively; all P < 0.001). (2) Multivariable logistic regression showed that ΔG30-0 was independently associated with increased ACR in postmenopausal women with NGR (odds ratio, 1.10; P = 0.048) but not in premenopausal women. (3) The main factor associated with ΔG30-0 was the early-phase glucose disposition index drawn from the multivariable linear regression, which explained approximately 19% and 28% of the variation of ΔG30-0 in premenopausal and postmenopausal women, respectively (both P < 0.001). In the NGR population, postmenopausal women have higher ΔG30-0 and ACR compared with premenopausal women. The relationship between ΔG30-0 and increased urine albumin excretion existed in postmenopausal women.

C-reactive Protein Is Directly Associated with Urinary Albumin-to-Creatinine Ratio

There are no studies that elucidate whether the role of inflammation in the increase of urinary albumin is independent, mediated by family history or by risk factors acquired during life in the offspring of subjects with type 2 diabetes. We undertook this study to evaluate whether elevated C-reactive protein (CRP) levels are independently associated with urinary albumin-to-creatinine ratio (UACR) in the offspring of subjects with diabetic nephropathy. A total of 64 healthy males and healthy nonpregnant females, offspring ofsubjects with diabetic nephropathy, aged 18-69 years, and with body mass index ≤35kg/m(2) were enrolled in a cross-sectional study. Hypertension, glucose metabolic disorders, metabolic syndrome, smoking, alcohol intake, chronic or acute infections, renal disease, neoplasm, cardiovascular disease, degenerative disease, intake of anti-inflammatory drugs, exercise, or sexual intercourse in the previous 72 h were exclusion criteria. Subjects with high-sensitivity CRP (hsCRP) levels ≥3.0 mg/dL were compared with a gender- and age-matched control group of subjects with hsCRP levels <3.0 mg/dL. The multivariate linear regression analysis showed that hsCRP (B= 0.50, β= 0.583, p= 0.02), total body fat (B= -2.80, β= 0.473, p= 0.03), BMI (B= -1.45, β= 0.390, p= 0.04) and waist circumference (B= 0.89, β= 0.407, p= 0.04) are predictorsfor elevation of UACR (Table 2). However, in the stepwise model only hsCRP (B= 0.674; β= 0.314; p= 0.04) remained significantly associated with UACR. Our results show that independent of the primary risk factors, elevated hsCRP levels are associated with UACR.

Increases in urinary albumin and beta2-microglobulin are independently associated with blood pressure in the Japanese general population: the Takahata Study

Essential hypertension is a multifactorial disorder and a risk factor for renal failure and cardiovascular disease. Recently it was hypothesized that subtle acquired renal injury such as renal microvascular and tubulointerstitial damage induces salt-sensitive hypertension. The objective of this study was to examine the relationship between blood pressure and renal abnormalities in the Japanese general population. The participants in this community-based, cross-sectional study were 1,965 subjects over 40 years old, without renal insufficiency and antihypertensive medication. Urine albumin-creatinine ratio (UACR) and beta2-microglobulin-creatinine ratio (UBCR) were measured in single spot urine samples, as markers of renal microvascular and tubulointerstitial damage, respectively. Multiple linear regression analysis showed a significant positive correlation of blood pressure with UACR and UBCR, but not with estimated glomerular filtration rate. In multiple logistic regression analysis, the increases in UACR and UBCR were independently associated with hypertension, after adjustment for possible confounders. Higher levels of UACR (≥ 5.9 mg g(-1)) and UBCR (≥ 145 μg g(-1)) were associated with a significantly higher risk of hypertension, compared with UACR ≤ 5.8 mg g(-1) and UBCR ≤ 84.5 μg g(-1), respectively. Furthermore, there was a positive relationship between urinary sodium excretion and blood pressure in subjects with high UBCR tertile. This study showed that the increases in urinary albumin and beta2-microglobulin were independently associated with blood pressure in a general population. These renal abnormalities may be differentially related to the development of hypertension.

Association of Kidney Function and Metabolic Risk Factors With Density of Glomeruli on Renal Biopsy Samples From Living Donors

To test the hypothesis that kidney function and metabolic risk factors are associated with glomerular density on renal biopsy samples from healthy adults. This study compared glomerular density with predonation kidney function, blood pressure, and metabolic risk factors in living kidney donors at Mayo Clinic in Rochester, MN, from May 10, 1999, to February 4, 2009. During implantation of the kidney allograft, an 18-gauge core needle biopsy sample of the renal cortex was obtained, sectioned, and examined by pathologists. Glomerular density was determined by the number of glomeruli (normal and sclerotic) divided by area of cortex. The study sample of 1046 kidney donors had a mean of 21 glomeruli (0.8 sclerotic glomeruli) and a glomerular density of 2.3 glomeruli per square millimeter. In a subset of 54 donors, glomerular density inversely correlated with the mean glomerular area (r(s) = -0.28). Independent predictors of decreased glomerular density were older age, increased glomerular filtration rate, family history of end-stage renal disease, increased serum uric acid, and increased body mass index. Increased urine albumin excretion, hypertension, decreased high-density lipoprotein cholesterol, and metabolic syndrome were also associated with decreased glomerular density after age-sex adjustment. These associations were not explained by the presence of glomerulosclerosis, tubular atrophy, interstitial fibrosis, or arteriosclerosis on the renal biopsy sample. In older donors, decreased glomerular density was attenuated by an increased prevalence of glomerulosclerosis and tubular atrophy. Decreased glomerular density is associated with many different kidney function and metabolic risk factors among relatively healthy adults and may represent an early state of increased risk of parenchymal injury.

Impaired exercise tolerance is associated with increased urine albumin excretion in the early stages of essential hypertension

Our aim was to investigate the relationship between impaired exercise capacity and albumin excretion level in the setting of never treated essential hypertension. For this purpose, 338 consecutive essential hypertensives (52 ± 8.5 years, 227 males, office BP = 148.6/96.1 mmHg) performed a negative for myocardial ischemia, maximal treadmill exercise testing and were classified based on the gender specific median value of the amount of metabolic equivalents (METs) achieved (10.1 ml/kg/min for women and 11 ml/kg/min for men) as fit (n = 177) and unfit (n = 161). All the participants underwent 24-h ambulatory BP monitoring, complete echocardiographic study including left ventricular diastolic function evaluation and determination of albumin to creatinine ratio (ACR) on two non-consecutive morning spot urine samples. Unfit hypertensives compared to the fit ones were older by 4.5 years (p < 0.001) and had greater waist circumference by 4.5 cm (p < 0.001), body mass index by 1.3 kg/m(2) (p = 0.001), 24-h pulse pressure by 3.0 mmHg (p = 0.005), ACR levels by 12.6% (p = 0.003) and prevalence of microalbuminuria (19.5% vs 10.3%, p = 0.007) while the differences in diastolic function indices lost significance after adjustment for confounders. By applying stepwise multivariate linear regression analysis in order to identify the predictors of METs, it was revealed that age (β = -0.338, p = 0.045), gender (β = 0.274, p = 0.045), body mass index (β = -0.230, p = 0.045) and logACR (β = -0.151, p = 0.004) were the only independent predictors of exercise capacity. Increased ACR is associated with diminished exercise capacity in the early stages of essential hypertension independently from adverse cardiac adaptations, further elucidating the adverse prognostic role of albuminuria in this setting.

Glomerular filtration rate and prevalence of chronic kidney disease in Wilms’ tumour survivors

Glomerular filtration rate (GFR) was evaluated in 32 Wilms’ tumour survivors (WTs) in a cross-sectional study using 99 Tc-diethylene triamine pentaacetic acid (99 Tc-DTPA) clearance, the Schwartz formula, the new Schwartz equation for chronic kidney disease (CKD), cystatin C serum concentration and the Filler formula. Kidney damage was established by beta-2-microglobulin (B-2-M) and albumin urine excretion, urine sediment and ultrasound examination. Blood pressure was measured. No differences were found between the mean GFR in 99 Tc-DTPA and the new Schwartz equation for CKD (91.8 ± 11.3 vs. 94.3 ± 10.2 ml/min/1.73 m2 [p = 0.55] respectively). No differences were observed between estimated glomerular filtration rate (eGFR) using the Schwartz formula and the Filler formula either (122.3 ± 19.9 vs. 129.8 ± 23.9 ml/min/1.73 m2 [p = 0.28] respectively). Increased urine albumin and B-2-M excretion, which are signs of kidney damage, were found in 7 (22%) and 3 (9.4%) WTs respectively. Ultrasound signs of kidney damage were found in 14 patients (43%). Five patients (15.6%) had more than one sign of kidney damage. Eighteen individuals (56.25%) had CKD stage I (10 with signs of kidney damage; 8 without). Fourteen individuals (43.75%) had CKD stage II (6 with signs of kidney damage; 8 without). The new Schwartz equation for CKD better estimated GFR in comparison to the Schwartz formula and the Filler formula. Furthermore, the WT survivors had signs of kidney damage despite the fact that GFR was not decreased below 90 ml/min/1.73 m2 with 99 Tc- DTPA.