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Urinary albumin excretion rate and glomerular filtration rate in single-kidney type 2 diabetic patients.

OBJECTIVE: To evaluate the urinary albumin excretion rate (UAER) and the glomerular filtration rate (GFR) of single-kidney type 2 diabetic patients (SKD) and of single-kidney non-diabetic patients (SKN). RESEARCH DESIGN AND METHODS: Patients who had only one kidney for at least 5 years, with no renal disease or hypertension at the time of the nephrectomy and with no calculus or systemic disease at the time of the evaluation, were included in this controlled cross-sectional study A total of 20 SKD (8 men, age 62 +/- 9 years; diabetes duration 8.5 +/- 7 years), 17 SKN (2 men, age 57 +/- 13 years), and 184 type 2 diabetic patients who were matched to the single-kidney diabetic group for age, sex, and BMI were studied. UAER was measured by immunoturbidimetry in timed 24-h sterile urine, and GFR was determined by the 51Cr-EDTA single-injection method. RESULTS: SKD patients presented a higher proportion (8 of 20, 40%) of microalbuminuria (UAER 20-200 microg/min) than SKN patients (3 of 17, 17.6%) and type 2 diabetic patients (37 of 184, 20%). SKD patients presented a higher proportion of macroalbuminuria (UAER >200 microg/min; 6 of 20, 30%) than SKN patients (1 of 17, 6%) but were similar to type 2 diabetic patients (43 of 184, 23%). The GFRs of normoalbuminuric SKN (71.7 +/- 21.4 ml x min(-1) x 1.73 m(-2)) and SKD patients (73.0 +/- 21.5 ml x min(-1) x 1.73 m(-2)) were similar but higher than the one-kidney GFR (GFR / 2) of the age-, sex-, and BMI-matched normal individuals (50.5 +/- 9.0 ml x min(-1) x 1.73 m(-2)) and normoalbuminuric type 2 diabetic patients (54.0 +/- 11.6 ml x min(-1) x 1.73 m(-2)). CONCLUSIONS: Increased GFR related to single-kidney status confers an increased risk of developing renal disease in the presence of diabetes.

Adult↗

Urinary albumin excretion rate and glomerular filtration rate in the prediction of diabetic nephropathy; a long-term follow-up study of childhood onset type-1 diabetic patients.

BACKGROUND: Predictors of diabetic nephropathy are only partly known. The role of glomerular hyperfiltration is much discussed. We have studied the cumulative incidence of micro and macroalbuminuria and the predictive value of glomerular filtration rate (GFR) and screening value of albumin excretion rate (AER) in type-1 diabetes. METHODS: A cohort of diabetic children was followed up at a mean duration of 29+/-3 years. All 75 children treated in one hospital with diabetes duration > or =8 years were prospectively followed for 8 years examining GFR, AER, blood pressure and HbA1c. After another 8-10 years, 60 of them were traced for endpoint follow-up. RESULTS: Seven patients (12%) developed macroalbuminuria, i.e. persistent overnight AER>200 mg/min, 12 (20%) developed persistent microalbuminuria (AER 15-200 mg/min) and 17 (28%) transient microalbuminuria (>15 mg/min on two consecutive occasions, normalized at endpoint). One baseline screening value of 24-h AER>15 mg/min predicted 93% of patients with persistent micro or macroalbuminuria. The negative predictive value was 78%. Six of seven macroalbuminuric and 10 of 12 microalbuminuric patients had a baseline GFR above the normal limit of the method (> or =125 ml/min/1.73 m(2)). When adjusted for diabetes duration, increased GFR predicted macro or microalbuminuria (odds ratios=5.44, P=0.04). The positive predictive value for having an increased baseline GFR was 53%. The negative predictive value was 77%. Stratification for HbA1c did not change the effect of an increased GFR. CONCLUSIONS: At a mean diabetes duration of 29 years the cumulative incidence of macroalbuminuria was 12%; however, another 20% had persistent microalbuminuria. A screening value of 24-h AER >15 mg/min was a strong predictor, whereas increased GFR was a weaker but significant predictor for micro and macroalbuminuria.

Albuminuria↗

The glomerular filtration rate during pregnancy: saline infusion enhances the glomerular filtration rate in the pregnant rat.

The glomerular filtration rate (GFR) of pregnant rats is generally believed to exceed non-pregnant values. This notion is primarily based upon standard insulin clearances. However, the insulin clearance requires continuous infusion of insulin usually dissolved in saline. Since saline infusion per se in pregnancy may influence the GFR, in the present study the effect of saline infusion upon the GFR in pregnant as compared with cyclic rats was investigated using various methods. The standard insulin clearance was compared using the standard 51Cr-EDTA method which does not require saline infusion. Clearance of insulin dissolved in glucose (5% in distilled water) instead of saline was also tested, while the 51Cr-EDTA method was employed using additional fluid infusion with either saline or 5% glucose in distilled water in an identical manner as compared with the insulin method. The GFR was also studied in conscious rats using 51Cr-EDTA clearance with and without fluid infusion. The distribution volume of 51Cr-EDTA was measured in nephrectomized rats (pregnant and cyclic) with and without saline or glucose infusions. The results show a significant increase of the GFR in pregnant rats as compared with cyclic rats only when saline was infused during the measurement; thus, GFR measurements without fluid infusion or replacement of saline by glucose during the measurements did not show a significant increase of GFR in pregnant rats. The volume of distribution per gram body weight of 51Cr-EDTA after saline infusion, but not after glucose infusion, was significantly increased as compared with the values obtained without additional infusion. It is concluded that the increase of the GFR seen in pregnant rats when either the 51Cr-EDTA method or the insulin method is accompanied by saline loading is rather due to infusion of saline in the pregnant animal and not a result of the pregnant condition per se.

Animals↗

The relation between tissue kallikrein excretion rate, aldosterone and glomerular filtration rate in human pregnancy.

The changes in renal kallikrein synthesis through normal pregnancy and its relation to aldosterone excretion and the glomerular filtration rate was investigated. Overnight urinary kallikrein and aldosterone excretion rates and glomerular filtration rate were measured at 18 weeks, 34 weeks, term and postpartum in normal human pregnancy. Kallikrein excretion was raised at 18 weeks compared with the nonpregnant state (P < 0 x 001) but was significantly reduced at term. The reduction in renal kallikrein was not due to falling aldosterone concentration, which increased in the third trimester, compared with 18 weeks (P = 0 x 002) and remained elevated at term compared with the nonpregnant state (P < 0 x 001). Glomerular filtration rate remained elevated at term despite the reduced kallikrein excretion rate. These data are consistent with the hypothesis that increased aldosterone production is one factor responsible for increased kallikrein synthesis which contributes to elevated glomerular filtration rate in early pregnancy. Other factors clearly inhibit renal kallikrein production at term. In the face of plasma volume expansion associated with increased mineralo-corticoid production, the effects of reduced kallikrein synthesis at term on glomerular perfusion and reabsorption of sodium by the distal tubule may predispose to blood pressure elevation in late pregnancy.

Aldosterone↗

Short term effect of an aldose reductase inhibitor on urinary albumin excretion rate (UAER) and glomerular filtration rate (GFR) in type 1 diabetic patients with incipient nephropathy.

OBJECTIVE: Increased activity of the enzyme aldose reductase in the polyol pathway, occurring with hyperglucaemia, has been implicated in the development of late diabetic complications. The effect of an aldose reductase inhibitor (Ponalrestat) on renal function in type 1 diabetes with incipient nephropathy (urinary albumin excretion rate > 20 micrograms.min-1) was evaluated. RESEARCH DESIGN AND METHODS: Thirty Type 1 diabetic patients (age: 34.4 +/- 3.1 yrs; diabetes duration 13.1 +/- 1.3 yrs) were treated with 600 mg of Ponalrestat per day for 3 months using a randomized double blind placebo controlled crossover design. Urinary albumin excretion rate and glomerular filtration rate were measured. RESULTS: Twenty three patients completed the entire study. Compared to placebo, there was no significant change in urinary albumin excretion rate and glomerular filtration rate during the Ponalrestat treatment period. Blood pressure and HbA1 were also unchanged during the placebo and Ponalrestat periods. Treatment with Ponalrestat appeared to be safe and there were no side effects. CONCLUSION: We conclude that three months aldose reductase inhibition with Ponalrestat had no effect on urinary albumin excretion rate and glomerular filtration rate in Type 1 diabetic patients with incipient nephropathy.

Adolescent↗

Nitrendipine and enalapril improve albuminuria and glomerular filtration rate in non-insulin dependent diabetes.

The effects of 3, 15, and 27 months of treatment with nitrendipine (10 to 40 mg/day) and enalapril (5 to 20 mg/day) on diastolic blood pressure (DBP), overnight urinary albumin excretion (UAE) rate, glomerular filtration rate (GFR), and renal plasma flow (RPF) were studied prospectively in a parallel group design in 13 microalbuminuric non-insulin dependent diabetic patients with mild hypertension and biopsy-proven diabetic glomerulopathy. Throughout the study period DBP decreased in both groups to < 95 mm Hg. At three months UAE, GFR, and RPF did not change significantly. At 15 and 27 months UAE (microgram/min, geometric mean and 95% C.I.) decreased respectively from 47.4 (23.4 to 95.9) to 28.6 (10.3 to 79.4), and to 22.3 (10.9 to 45.2; P = 0.0005) with nitrendipine, and from 58.3 (30.3 to 110.9) to 44.1 (22.9 to 84.8), and to 14.7 (4.4 to 49.3; P = 0.0025) with enalapril. Four patients in each group were normoalbuminuric at 27 months and none became macroalbuminuric. At 15 months the GFR (ml/min/1.73 m2, mean +/- SD) increased from 69.5 +/- 15.2 to 96.6 +/- 22.0 (P < 0.05) with nitrendipine and from 58.9 +/- 10.7 to 78.5 +/- 11.0 (P < 0.05) with enalapril. At 27 months the GFR was still numerically higher that at baseline either with nitrandipine (81.2 +/- 7.8) and with enalapril (79.9 +/- 17.7) (P = 0.7). The RPF (ml/min/1.73 m2, mean +/- SD) at baseline and at 27 months was comparable either with nitrendipine (456.6 +/- 165.3 vs. 400.9 +/- 112.9) and with enalapril (400.3 +/- 81.3 vs. 399.0 +/- 123.7). Both treatments were well tolerated. This is the first evidence that long-term effective control of arterial blood pressure by a calcium channel blocker or by an angiotensin converting enzyme inhibitor, in addition to reducing albuminuria, also improves GFR in incipient nephropathy.

Adult↗

Systolic blood pressure relates to the rate of decline of glomerular filtration rate in type II diabetes.

OBJECTIVE: To relate deterioration in kidney function to some potential cardiovascular risk factors in type II diabetic patients. RESEARCH DESIGN AND METHODS: Twenty-four normoalbuminuric and 13 microalbuminuric patients completed a 3.4-yr prospective observational study. Glomerular filtration rate, urinary albumin excretion rate, blood pressure, glycemic control, and lipids were measured on entry and at the end of the study. Of the patients, 19 normoalbuminuric and 8 microalbuminuric (73%) patients had no history of antihypertensive treatment. RESULTS: The glomerular filtration rate was significantly reduced during the follow-up period (-1.34 +/- 0.54 ml.min-1.1.73 m-2 [mean +/- SE], P < 0.02). The rate of decline varied considerably in normoalbuminuric and microalbuminuric patients (from -13.5 to 4.3 and from -7.0 to 4.2 ml.min-1.1.73 m-2 per year, respectively) but was on average not accelerated in normoalbuminuric or microalbuminuric patients (-1.3 +/- 0.7 and -1.5 +/- 0.8 ml.min-1.1.73 m-2 per year, respectively). Significant correlations were observed between the glomerular filtration rate fall rate and initial systolic blood pressure (r = -0.47, P < 0.01; patients without antihypertensive treatment: r = -0.42, P = 0.03) but not diastolic blood pressure. In a stepwise multiple linear regression analysis, baseline systolic blood pressure significantly determined the fall rate of the glomerular filtration rate (regression coefficient = -0.050, SE = 0.018, P = 0.011; patients without antihypertensive treatment: regression coefficient = -0.047, SE = 0.021, P = 0.030). CONCLUSIONS: In these type II diabetic patients neither normoalbuminuria nor microalbuminuria are at an average associated with an accelerated decline in kidney function. Still, systolic blood pressure is a determining factor for the rate of decline in the glomerular filtration rate. A longer follow-up time with consecutive glomerular filtration rate measurements are needed to determine the long-term implications of normoalbuminuria and microalbuminuria on kidney function in type II diabetic patients.

Aged↗

Serum cystatin C as a marker of glomerular filtration rate.

PURPOSE OF REVIEW: Glomerular filtration rate is widely accepted as the best overall measure of kidney function. Currently available methods to estimate glomerular filtration rate have strengths and limitations. Cystatin C is a novel endogenous filtration marker being considered as a potential replacement for serum creatinine. This review summarizes the currently available glomerular filtration rate estimating equations based on cystatin C and the literature comparing cystatin C and creatinine as filtration markers. RECENT FINDINGS: In most cystatin C estimating equations, inclusion of age and sex did not substantially improve their performance. Equations yield different glomerular filtration rate estimates for the same level of cystatin C. Variation among equations may be due to differences among the assays or populations in the individual studies. Studies comparing cystatin C with creatinine or creatinine-based estimating equations show heterogeneous results, with some showing improved performance and others showing equivalent performance even in similar populations. These heterogeneous results may be due to inappropriate comparisons between equations developed in one population with those developed in another, or to the differences between assays or population characteristics. SUMMARY: Cystatin C shows promise as an alternative to serum creatinine but several important questions remain before it can be recommended for use in clinical practice.

Aged↗

Comparison of two formulae for estimation of glomerular filtration rate in children.

Glomerular filtration rate (GFR) was measured in 216 studies in 151 children using the cimetidine protocol. This was compared with the GFR calculated using Léger's pharmacokinetic equation and with that calculated using k*L/[Cr](s )(constant x length in centimeters divided by serum creatinine concentration). The GFR calculated using the equation GFR=k*L/[Cr](s) yielded a closer approximation to the measured GFR than that using Léger's pharmacokinetic equation. Currently there is focus on screening children for decreased GFR to identify those with asymptomatic chronic kidney disease at a time when intervention may delay progression to chronic renal failure. This study showed close approximation of the calculated GFR with the measured GFR using the equation GFR=k*L/[Cr](s), when the values for k were determined in the laboratory in which creatinine was measured.

Adolescent↗

Single-injection inulin clearance for routine measurement of glomerular filtration rate in cats.

Glomerular filtration rate (GFR) was determined in 53 cats using an inulin single-injection method. Thirty healthy young adult cats were used to establish normal values. The procedure was also used in 23 cats that were either older than 10 years or had borderline serum creatinine levels. The total clearance was calculated from the decay of the serum inulin concentration after injection of 3000 mg/m(2)body surface area using a two-compartment model. Concomitant inulin and iohexol clearance in nine cats showed excellent correlation between the two methods. Calculated normal values for GFR in 30 healthy cats were 35.9-58.5 (median 46.0) ml/min/m(2)or 2.07-3.69 (median 2.72) ml/min/kg. A few cats with normal creatinine or blood urea nitrogen levels were detected as having reduced GFR and therefore being in a state of early renal dysfunction. The study indicates that single-injection inulin clearance is a valuable tool for routine GFR measurement in cats. An "inulin excretion test" using only one blood sample 3h after the administration of 3000 mg/m(2)body surface area could prove an attractive alternative for the assessment of renal function in daily practice.

Animals↗

Evaluation of a single injection of 99mTc-labeled diethylenetriaminepentaacetic acid for measuring glomerular filtration rate in horses.

Glomerular filtration rate (GFR) was measured in 12 clinically normal horses, using the standard inulin clearance method, and values were compared with values for 2 methods, using a single rapid IV injection of 99mTc-labeled diethylenetriaminepentaacetic acid (99mTc-DTPA). The first 99mTc-DTPA method used a 2-compartment model to calculate GFR blood clearance of the tracer. The second method used sequential digital gamma camera images of the kidneys to determine fractional accumulation of the total dose of the tracer in the kidneys (percentage of injected dose, gamma camera) from 0 to 10 minutes after radionuclide administration. Linear correlation among the 3 methods was determined. Mean (+/- SD) GFR, using the inulin clearance method, was 154.67 +/- 42.28 ml/min/100 kg of body weight. Mean GFR, using the 2-compartment blood clearance curve, was 146.92 +/- 27.49 ml/min/100 kg. Mean GFR, using percentage of injected dose (gamma camera method) was 154.7 +/- 22.00 ml/min/100 kg. The percentage of injected dose (gamma camera method) did not correlate significantly to the inulin clearance results. However, a significant (r = 0.666, P less than 0.018) correlation was observed between the inulin method and the 99mTc-DTPA blood clearance method. Significant (P less than 0.0001) difference also was observed in the split function of the equine kidneys, with GFR of the right kidney contributing 60.1 +/- 9.12% of the total function, as determined by 99mTc-DTPA gamma camera imaging. Because the 99mTc-DTPA blood clearance method does not require urine collection, it may be a more practical procedure to measure GFR in the horse.

Animals↗

Glomerular filtration rate estimation in renal transplant patients based on serum cystatin-C levels: comparison with other markers of glomerular filtration rate.

PURPOSE: The assessment of glomerular filtration rate (GFR) is the most commonly used test of renal function. Cystatin-C, a cysteine protease inhibitor, which can be measured by light-scattering immunoassay, possesses many of the attributes required of the ideal GFR marker. Conversely, many endogenous markers that are widely used for the estimation of GFR such as serum creatinine (SCr) are not ideal. The present study was undertaken to evaluate the clinical application of serum cystatin-C (CysC) as a new marker of GFR in renal transplant patients. METHODS: Eighteen patients (9 men) were enrolled in the study (mean age: 46.35, range: 31-67 years) to measure serum CysC levels and compare them, with SCr, creatinine clearance (CCr), as well as the Cockcroft-Gault equation (CG) or the MDRD as indicator of GFR. Spearman's correlation coefficient was used to determine the relationship between CysC and other markers. RESULTS: There was a significant negative correlation between serum CysC and CCr (r = -0.768). Moreover, the CysC level was negatively correlated with CG (r = -0.854), positively correlated with SCr (r = 0.629), and negatively correlated with MDRD (r = -0.604). CONCLUSIONS: These results indicate that measurement of serum cystatin-C was useful and accurate to estimate GFR in renal transplant patients. The recent literature confirms our data although there are concerns about nonrenal influence on this test. Although serum CysC can generally be recommended as a marker for GFR, our study is still in progress seeking to validate the conclusions in a larger number of patients.

Adult↗

Measurement of the ratio of glomerular filtration rate to plasma volume from the technetium-99m diethylene triamine pentaacetic acid renogram: comparison with glomerular filtration rate in relation to extracellular fluid volume.

Individual kidney glomerular filtration rate (IKGFR) can be measured from the renogram from the rate of uptake of technetium-99m diethylene triamine penta-acetic acid (99mTc-DTPA). A blood sample is required to derive IKGFR in millilitres per minute, which is then usually normalised to body surface area. We describe a technique which does not require a blood sample, is already normalised for plasma volume and uses the robust Patlak plot for measuring renal uptake. The rate of kidney uptake, dR(t)/dt, at time = 0, as a fraction of the injected dose, is equal to the fraction of the plasma volume (PV) filtered per minute, i.e. IKGFR/PV. The gradient dR(0)/dt cannot be accurately measured directly but is equal to [alpha .LV(0)], where alpha is the renal uptake constant (proportional to IKGFR) and LV is the count rate over a left ventricular ROI. LV(0) was obtained by extrapolation of LV(t), while alpha is the slope of the Patlak plot up to 3 min. GFR/PV (i.e. right plus left kidneys) in patients with normal renal function was about 0.04 min-1, as would be expected from normal values of GFR (120 ml/min) and plasma volume (3 l). GFR/PV correlated significantly with the ratio of GFR to extracellular fluid volume (ECV), measured from the terminal exponential of the plasma clearance curve (GFR/PV = 3.2.GFR/ECV + 5.3 ml/min/l [r = 0.82, n = 82]). GFR/PV (r = 0.74) and GFR/ECV (r = 0.82) both correlated inversely and non-linearly with plasma creatinine in 43 studies where the measurement was made within 1 week of the 99mTe-DTPA study.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Physiological time and the measurement of glomerular filtration rate.

Diverse physiological timescales in different animals can have an important influence on the measurement of biological variables. In vertebrates, the absolute and relative rates of glomerular filtration span several orders of magnitude. These differences have important implications for the logistics of measurement protocols in different species. A simple model is used to examine the importance of physiological time to the measurement of glomerular filtration rate.

Animals↗