Lower Glomerular Filtration Rate Values Research Articles

EFFECTS OF SMOKING ON CIRCADIAN ARTERIAL BLOOD PRESSURE PROFILE IN PATIENTS WITH NON-ST-SEGMENT ELEVATION ACUTE CORONARY SYNDROME AND CHRONIC KIDNEY DISEASE

The paper presents the results of a study of the effects of smoking on circadian arterial blood pressure (ABP) profile in patients with Non-ST-Segment Elevation Acute Coronary Syndrome (NSTE-ACS) and Chronic Kidney Disease (CKD).
 Aim. The research aims at studying the features of circadian blood pressure monitoring (CBPM) in patients with NSTE-ACS and CKD, smoking-dependent.
 Materials and Methods. The study includes 70 patients with NSTE-ACS and CKD aged 35 to 75 years. The patients were divided into 2 groups: Group I - 35 smokers (mean age - 60.09±1.66 years), Group II - 35 individuals who have never smoked (mean age - 62.31±1.04 years). The circadian blood pressure monitoring was carried out on the second day of hospital admission after stabilization of the patient's condition. The following indicators have been determined: systolic blood pressure (SBP) - daytime, nighttime, and average daily (24 hours) (SBPd, SBPn, and SBPav); diastolic blood pressure (DBPd, DBPn, and DBPav); pulse pressure (PBPd, PBPn, and PBPav); time index (TI) for SBPd and SBPn (SBPd TI and SBPn TI) and DBP (DBPd TI and DBPn TI); heart rate (HR). To study the renal functional status in the examined patients, the urine albumin-creatinine ratio (ACR) was determined using the semi-quantitative method. The glomerular filtration rate (GFR) was calculated using the CKD-EPI Creatinine Equation.
 Results. Mean SBP, DBP, and PBP levels were significantly higher in Group I patients compared to Group II patients: SBPd - by 5.10% (p<0.05), SBPn - by 6.60% (p<0.05); DBPd - by 9.60% (p=0.01), DBPn - by 14.10% (p<0.05); PBPd - by 7% (p=0.05), PBPn - by 8.50% (p<0.05). The mean TI value also turned out to be significantly higher in the group of smokers (I) versus non-smokers (II): SBPd TI - by 55.50% (p<0.01), SBPn TI - by 58.90% (p<0.01), DBPd TI - by 57.50% (p<0.01), DBPn TI - by 46.30% (p<0.01). The HR was higher by 10.80% in Group I patients compared to Group II patients (p<0.01). The mean GFR level in smokers is 13.00% lower than in non-smokers (p<0.05). A 57% significantly higher ACR level was found in the group of smokers (Group I) compared to non-smokers (Group II) (p<0.01).
 Conclusions. Mean SBP, DBP, PBP, TI, and HR levels were significantly higher in the group of smokers with NSTE-ACS and CKD. In the same Group, more distinct signs of kidney injury were found, namely, lower GFR values and higher ACR values, which indicates the probable adverse effect of smoking on ABP regulation and renal microvasculature.

Colistin treatment in older adults: why should we know more?

Objectives We aimed to investigate the risk factors of colistin-associated nephrotoxicity in patients older than 65 years treated in the palliative care unit. Methods 119 palliative care patients who received intravenous colistimethate for at least 7 days were included in the study. The estimated glomerular filtration rate (GFR) was calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) 2021 equation. Data were obtained from the hospital information system. Results The mean age of the participants was 76.7 ± 9.9 years and 49.4% were female. Of the 119 patients, 57 had colistin-induced nephropathy (CIN) according to Kidney Disease: Improving Global Outcomes (KDIGO) criteria. The rate of CIN was higher in women than in men. The baseline phosphate level was higher in the CIN (+) group than in the CIN (–) group. The lower GFR values in patients with pneumonia persisted at days 14 and 30, whereas the lower GFR in patients without pneumonia did not. According to multivariate logistic regression, female gender and baseline phosphate level ≥ 4.5 mg/dl were found as independent variables for the development of nephropathy. Conclusions The creatinine levels of the patients with pneumonia and CIN did not improve after nephrotoxicity, whereas the creatinine levels of the other patients without pneumonia and CIN did. Female gender and baseline phosphate were independent risk factors for CIN. Prolonged kidney failure may lead to a more difficult clinical follow-up process for clinicians. Therefore, clinicians should be aware of persistent renal insufficiency in older patients with pneumonia receiving colistimethate.

Low glomerular filtration rate values are associated with higher TSH in an elderly population at high cardiovascular disease risk.

Hypothyroidism is associated with impaired glomerular filtration rate (GFR), a recognized cardiovascular disease (CVD), and mortality risk factor. In older adults, this association remains unexplored. We aimed to determine the relationship of elevated TSH with GFR in an elderly population at high CVD risk. Older adults (age>65ys) with high CVD risk defined by two or more CVD risk factors: smoking (S), high blood pressure (HBP), high total cholesterol, low HDL cholesterol, diabetes (DM), metabolic syndrome or previous cardiovascular event, were prospectively included at our ambulatory Endocrine Clinic. Patients under levothyroxine or thyroid disease were excluded. TSH> 6mU/l defined subclinical hypothyroidism (ScH) with normal free T4 levels. Estimated GFR was calculated by the Berlin-Initiative Study (BIS)-1 formula for elderly population. Urinary albumin to creatinine ratio (uACR), IL-6 and TNF-α, and Carotid intima-media thickness (CIMT) were also determined. The U Mann-Whitney test, the Spearman test, and multiple linear regression were used as statistical tests. Finally 246 patients (68% females) were included and 20 (8%) had ScH. This group, was older (median, Q1-Q3: 77,72-78; 72,68-77 years, p=0.01) and DM was less frequent than in the euthyroid group (35 vs 58%, p=0.039). Lower fasting glucose (-20%,p=0.01), GFR (-14%,p=0.01) and freeT4 (-10%,p<0.001) were found compared to euthyroid patients. A higher prevalence of Kidney failure was found in ScH (80 vs. 46%, p=0.003) vs. euthyroid individuals. Significant correlations with GFR were detected: age (r-0.482,p<0.001), TSH (r-0.172,p=0.004), IL-6 (r-0.150,p=0.047), TNF-α (r-0.274,p<0.001), uACR (r-0.170,p=0.009) and CIMT(r-0.189,p=0.004). By multiple linear regression, in a model adjusted by age, sex, BMI, uACR, S, DM, TNF-α and HBP, TSH (Bst -0.14, p=0.023, R2 = 0.25) was found an independent predictor of GFR. In older adults with high CVD risk, ScH is associated with lower renal function, and this relationship is present regardless of other cardiometabolic risk factors. These results suggest that ScH could contribute to low GFR and excess CVD risk, although this hypothesis should be addressed in longitudinal studies.

Lower estimated glomerular filtration rate at admission is associated with a worse outcome in older patients with hip fracture who undergo surgical treatment

We assessed the relationship of estimated glomerular filtration rate values at hospital admission on the outcome of surgically treated older adults who had suffered a hip fracture. Prospective study that included patients > 65 years of age, surgically treated for primary hip fracture, with no pathologic or high-energy trauma aetiology admitted to a tertiary teaching hospital between 2018 and 2019. We stratified patients based on their estimated glomerular filtration rate at admission and examined its association to demographic and clinical variables, including 90-day post-discharge mortality. The study included 942 hip fracture patients. Lowered estimated glomerular filtration rate was significantly associated to a worsening of the functional status, higher incidence of medical postoperative complications, higher postoperative renal dysfunction, and greater number of blood transfusions. Mortality displayed a staircase pattern, increasing with decreasing estimated glomerular filtration rate. Patients with estimated glomerular filtration rate <60 had significantly higher mortality at 90 days after discharge. In-hospital mortality rate was 10.7% in hip fracture patients with chronic kidney disease who experienced a significant variation in the estimated glomerular filtration rate (>5 mL/min/1.73m2) on admission in comparison to baseline values. Older adult patients treated for hip fracture with lower glomerular filtration rate values have poorer functional status and worse prognosis. A significant clinical variation of estimated glomerular filtration rate upon hospital admission for hip fracture may be associated with increased in-hospital mortality of chronic kidney disease patients.

New developments and future prospects in the field of glomerular filtration rate estimation

Glomerular filtration rate (GFR) is estimated from equations based on serum or plasma concentrations of endogenous markers (creatinine and/or cystatin C), and demographic data (age, sex, ± ethnicity). These equations are accurate at the population level, but often inaccurate at the individual level. The creatinine-based Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) equation published in 2009 (CKD-EPIcr-2009), and the CKD-EPI equation published in 2012 based on creatinine and cystatin C, were recalibrated in 2021 to remove their dedicated race correction factors for black American subjects. All creatinine-based CKD-EPI equations overestimate true GFR in subjects younger than 30 years. The Full Age Spectrum (FAS) equation, applicable across the entire age spectrum (pediatrics to old age), solved this problem, but remained suboptimal at low GFR values. The European Kidney Function Consortium (EKFC) equation published in 2021 was an improvement of the FAS equation, which also includes the Q factor (median creatinine in the general population). EKFC is applicable across the age spectrum and is efficient at low and normal GFR values. The new creatinine-based CKD-EPI equation (CKD-EPIcr-2021) underestimates GFR in Black Americans and overestimates it in non-Black Americans. In European and African subjects, CKD-EPIcr-2021 overestimates true GFR and should not be adopted. The EKFC equation, which performs well in this population, also performs well in European Black subjects and in African subjects, provided dedicated Q factors are used.

Urinary albumin excretion and chronic kidney disease in children with vesicoureteral reflux

Albuminuria is a potential biomarker of chronic kidney disease (CKD) in various glomerular diseases. Vesicoureteral reflux (VUR) often progresses to CKD, and study is required of use of albuminuria as a biomarker for this condition. The aim of this study was to evaluate the association between albuminuria and glomerular filtration rate (GFR) or filtration fraction (FF) in children with VUR. In this retrospective study, renal parameters of 141 children with VUR were investigated, using inulin clearance, FF, and albuminuria. The association between urinary albumin to creatinine ratio (ACR), GFR, and FF was analyzed in a continuous manner by calculating the β coefficient, and also in a binary manner by calculating the OR. Using both continuous and binary analyses, ACR values were negatively and significantly associated to GFR values in patients with low, normal, or high FF values (Table). It was also positively and significantly associated with FF values in patients with low, normal or high GFR values (Table). No association was found between ACR and gender, VUR stages or laterality, number of urinary tract infection, presence of a single functional kidney, history of reflux surgery, or renal scars or hypertension. ACR is associated with CKD in patients with VUR. In addition, increased urinary albumin excretion cannot be completely and solely explained by decreased GFR and/or increased FF values. The two main limitations of this study are the crude assessment of renal scarring, which prevented finer analysis between albuminuria and renal scarring surface area, and that the study cohort may not be representative of the true VUR population. This study shows that albuminuria is associated with decreased renal function in patients with VUR and that it could be used to monitor renal function in this condition.

Non-Muscle Myosin Heavy Chain 9 Gene (MYH9) Polymorphism (rs4821481) is Associated with Urinary Albumin Excretion in Iranian Diabetic Patients

Background: Myosin heavy chain 9 (MYH9) gene polymorphisms have been implicated in different types of renal disease, as well as in nephropathy attributed to type 2 diabetes mellitus. Objectives: This study sought to analyze the association of MYH9 gene polymorphism (rs4821481) with diabetic nephropathy (DN), urine albumin excretion value, and glomerular filtration rate (GFR) in an Iranian diabetic population. Methods: This case-control study included 201 diabetic patients with and without DN, who were referred to the diabetes and metabolic center, Tehran, Iran. The allele and genotype frequencies of rs4821481 were determined using ARMS-polymerase chain reaction (ARMS-PCR). In both groups, blood levels of fasting glucose, HbA1c, urea, creatinine, uric acid, and lipids, as well as urine albumin and creatinine, were measured and GFR was calculated. Results: Patients who carried the rs4821481 polymorphism had significantly higher urinary excretion of albumin (P < 0.05) and insignificantly lower GFR values (P = 0.08). The frequency of rs4821481 SNP was 22.8 in patients without DN versus 28 in the DN group, which was not statistically significant. Only 2 and 3 of patients without DN and with DN, respectively, had two copies of the C allele. No significant association was found between the rs4821481 polymorphism and DN (OR 95% CI 1.56 0.79 - 3.08, P = 0.19). Conclusions: Although we found an association between MYH9 gene polymorphism and urinary albumin excretion, the results did not show a significant association between MYH9 polymorphism (rs4821481) and risk of DN in Iranian diabetic patients. A¯Â?½ 2016, Iranian Red Crescent Medical Journal.

Mechanisms of triple whammy acute kidney injury.

Pre-renal acute kidney injury (AKI) results from glomerular haemodynamic alterations leading to reduced glomerular filtration rate (GFR) with no parenchymal compromise. Renin-angiotensin system inhibitors, such as angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor antagonists (ARAs), non-steroidal anti-inflammatory drugs (NSAIDs) and diuretics, are highly prescribed drugs that are frequently administered together. Double and triple associations have been correlated with increased pre-renal AKI incidence, termed "double whammy" and "triple whammy", respectively. This article presents an integrative analysis of the complex interplay among the effects of NSAIDs, ACEIs/ARAs and diuretics, acting alone and together in double and triple therapies. In addition, we explore how these drug combinations alter the equilibrium of regulatory mechanisms controlling blood pressure (renal perfusion pressure) and GFR to increase the odds of inducing AKI through the concomitant reduction of blood pressure and distortion of renal autoregulation. Using this knowledge, we propose a more general model of pre-renal AKI based on a multi whammy model, whereby several factors are necessary to effectively reduce net filtration. The triple whammy was the only model associated with pre-renal AKI accompanied by a course of other risk factors, among numerous potential combinations of clinical circumstances causing hypoperfusion in which renal autoregulation is not operative or is deregulated. These factors would uncouple the normal BP-GFR relationship, where lower GFR values are obtained at every BP value.

Total plasma clearance versus urinary plasma clearance of 51Cr-EDTA in patients with cirrhosis with and without fluid retention

Background and aim. In patients with fluid retention, the total plasma clearance of 51Cr-EDTA (ClP) may overestimate the glomerular filtration rate (GFR). The present study was therefore undertaken in order to compare ClP with the urinary plasma clearance of 51Cr-EDTA (ClU) in patients with cirrhosis with and without fluid retention. Material and methods. A total of 136 patients with cirrhosis (24 without fluid retention, 112 with ascites) received a quantitative intravenous injection of 51Cr-EDTA followed by plasma and quantitative urinary samples for 5 hours. ClP was determined from the injected dose relative to the plasma concentration-time area, extrapolated to infinity. ClU was determined as urinary excretion relative to the plasma concentration-time area up to voiding. Results. In patients without fluid retention, the difference between ClP and ClU (ClP − ClU = ClΔ) was mean 4.5 mL/min/1.73 m2. In patients with ascites, ClΔ was significantly higher (17.6 mL/min/1.73 m2, p < 0.0001). ClΔ increased with lower values of GFR (r = − 0.458, p < 0.001). Repeated measurements of ClU in a subgroup of patients with fluid retention (n = 25) gave almost identical values. Different types of corrections of one-pool clearance were almost identical with ClP, except for higher clearance values, which were somewhat underestimated by the former. Conclusion. In patients with fluid retention and ascites ClP and corrected one-pool clearance overestimates GFR substantially. Although ClU may underestimate GFR slightly, patients with ascites should collect urine quantitatively in order to obtain a reliable measurement of GFR.

LG3 fragment of endorepellin is a possible biomarker of severity in IgA nephropathy

IgA nephropathy (IgAN), the most common primary glomerulonephritis, is characterized by deposition of IgA in the glomerular mesangium. The diagnosis of IgAN still requires a kidney biopsy that cannot easily be repeated in the same patient during follow-up. Therefore, identification of noninvasive urinary biomarkers would be very useful for monitoring patients with IgAN. We first used bidimensional electrophoresis (2DE) coupled to MALDI-TOF-TOF and Western blot to identify some urinary biomarkers associated with IgAN. Urine of IgAN patients showed an increase of albumin fragments, α-1-antitrypsin and α-1-β-glycoprotein, along with a decrease of a single spot that was identified as the laminin G-like 3 (LG3) fragment of endorepellin. The urinary proteomes of 43 IgAN patients were compared to those of 30 healthy individuals by ELISA. Quantification of LG3 confirmed a significant decrease in the urine of IgAN patients compared to healthy controls, except in ten patients in whom LG3 was increased. These ten patients had a more severe disease with lower glomerular filtration rate values. We found a significant inverse correlation between LG3 levels and glomerular filtration rate in the 43 patients with IgAN, which was not observed in 65 patients with other glomerular diseases including membranous nephropathy (23), lupus nephropathy (13), focal segmental glomerulosclerosis (15), diabetic nephropathy (14), and six patients with nonglomerular diseases. Therefore, we suggest that the LG3 fragment of endorepellin could be associated with IgAN severity and might be related to pathogenesis of IgAN.

Risks of Living Donor Nephrectomy

Introduction There is good evidence that long-term graft survival is superior when living donors are used for kidney transplantation. Nevertheless, an assessment of potential risks associated with living donation is of particular interest. Patients and Methods In this single-center study, we evaluated the renal function of 31 kidney living donors (1997–2003) at 2–13.2 years after nephrectomy. The purpose of this study was to evaluate perioperative complications, renal function, new-onset proteinuria, and hypertension. Results Living related donation was performed in all cases. The average time after donation was 5.7 ± 2.4 years. The mean age at nephrectomy was 46.3 ± 9.0 years (range, 25–64), and 26 (83.9%) donors were females. Twelve patients (29%) were older than 50 years. The left kidney was used in 25 patients (80.6%). Surgical complications occurred in 2 patients. Glomerular filtration rate (GFR) decreased from 116.9 ± 23 to 77.7 ± 19.2 mL/min/1.73 m 2 ( P < .001). Five patients (16.1%) developed a postdonation GFR between 50 and 60 mL/min/1.73 m 2. Patients with lower GFR values after uninephrectomy showed lower predonation values ( P < .05). Older patients (>50 years) displayed lower postdonation GFR than younger ones. We did not observe an increased prevalence of low postdonation GFR over time nor significant differences in protein excretion and blood pressure. Conclusions Living donor nephrectomy appears to be an acceptably safe intervention. Despite a reduction in GFR, the postdonation incidence of hypertension was low and proteinuria was not observed in any donor, even among previously hypertensive patients. Rigorous donor follow-up is recommended to identify persons at risk.

Left ventricular mass in hypertensive patients with mild‐to‐moderate reduction of renal function

Left ventricular hypertrophy (LVH) is an independent predictor of cardiovascular (CV) morbidity and mortality. The aim of the present study was to evaluate the relationship between LV mass and mild-to-moderate renal dysfunction in a group of non-diabetic hypertensives, free of CV diseases, participating in the Renal Dysfunction in Hypertension (REDHY) study. Patients with diabetes, a body mass index (BMI) of more than 35 kg/m(2), secondary hypertension, CV diseases and a glomerular filtration rate (GFR) of less than 30 mL/min per 1.73 m(2) were excluded. The final sample included 455 patients, who underwent echocardiographic examination and ambulatory blood pressure monitoring. There was a significant trend for a stepwise increase in LV mass, indexed by both body surface area (LVMI) and height elevated to 2.7 (LVMH(2.7)), with the declining renal function, that remained statistically significant after correction for potential confounders. The prevalence of LVH, defined either as LVMI of 125 g/m(2) or more or as LVMH(2.7) of 51 g/m(2.7) or more, was higher in subjects with lower values of GFR than in those with normal renal function (P < 0.001 in both cases). The multiple regression analysis confirmed that the inverse association between GFR and LVM was independent of confounding factors. The present study confirms the high prevalence of LVH in patients with mild or moderate renal dysfunction. In the patients studied (all with a GFR of 30 mL/min per 1.73 m(2)), the association between LVM and GFR was independent of potential confounders, including 24 h blood pressure load. Taking into account the negative prognostic impact of LVH, further studies focusing on a deeper comprehension of the mechanisms underlying the development of LVH in chronic kidney disease patients are needed.

Intima-media thickness is a useful marker of the extent of coronary artery disease in patients with impaired renal function

Objective The aim of the study was the assessment of intima-media thickness (IMT) in peripheral arteries (the carotid and the femoral artery) and its correlation with the extent of coronary artery disease (CAD). The second task was the analysis of the renal function's influence within IMT complex. Methods 231 patients (men, mean age 52.8), who had undergone coronary angiography due to symptoms of CAD were enrolled. The ultrasound measurement of IMT in the common carotid artery (CCA), carotid bulb and common femoral artery (CFA) was performed. The relationship between IMT, renal function and the extent of CAD was evaluated. Results Significantly higher values of IMT in the peripheral arteries were observed in patients with CAD than in those without (CCA—0.91 vs 0.61 mm, carotid bulb—1.31 vs 0.67, CFA—1.38 vs 0.63 respectively, p < 0.0001). The GFR values in the CAD patients significantly negatively correlated with IMT complex in CCA ( p < 0.001) and carotid bulb ( p < 0.05). Lower values of GFR in patients with three-vessel disease were observed than in those patients with one- or two-vessel disease ( p < 0.05). In multifactoral analysis (post-hoc NIR test) we found that glomerular filtration rate (GFR) is strongly determined by age ( p < 0.0001), BMI ( p < 0.0001), value of carotid intima-media thickness ( p < 0.001), value of IMT in the carotid bulb ( p < 0.02) and the treatment with ACE-I ( p < 0.05). In multifactoral analysis we did not find any statistical influence of lipid profile and glucose disturbances on GFR. Conclusions Higher peripheral artery IMTs in patients with CAD than in those without and patients with three-vessel disease indicate that IMT may be used as an early marker of atherosclerosis and reflect the severity of CAD. A significant negative correlation between the value of a GFR and the IMT confirmed the usefulness of this noninvasive method for the estimation of preclinical stages of atherosclerotic changes’ development in patients with impaired renal function.

Role of Glyceryl Trinitrate, a Nitric Oxide Donor, in the Renal Ischemia-Reperfusion Injury of Rats

Background/Aims: Ischemia-reperfusion injury is a serious clinical situation which can cause serious morbidity and mortality. An experimental renal ischemia-reperfusion injury model was designed to evaluate the role of glyceryl trinitrate (GTN) on renal function and histology. Methods: 50 Wistar albino rats were used in our study. Five groups were formed: (1) sham-control group; (2) acute renal ischemia (ARI) group with placebo (0.9% NaCl) infusion; (3) GTN infusion with a 75 µg/kg/min dose prior to ARI was administered; (4) GTN infusion with a 150 µg/kg/min dose prior to ARI was given, and finally (5) 150 µg/kg/min GTN infusion after the ARI period was applied. Serum BUN and creatinine levels were measured for evaluation of renal function. T_max-sec, glomerular filtration rate (GFR), and T_max-min results following a ^99mTc-DTPA diuretic renal scintigraphy were used. Histological examination was performed on nephrectomy specimens. Results: Groups 2 and 5 showed higher BUN, creatinine, and lower GFR values than the other groups (p = 0.0001). There was no difference in BUN, creatinine, and GFR levels between groups 2 and 5 (p = 0.971, p = 0.739, p = 0.393). Also the T_max-sec values were higher in groups 2 and 5 compared with the other groups (p = 0.0001). The presence of tubular necrosis was different between groups and was higher in groups 2 and 5 (p = 0.002). Conclusion: The application of GTN, a nitric oxide donor, has caused significant improvement in renal function when applied prior to an experimentally designed renal ischemia-reperfusion model. But administration of GTN had no effect after occurrence of ischemia.

NORMAL HOMOCYSTEINE LEVELS IN WELL‐FUNCTIONING OLDEST‐OLD INDIVIDUALS DESPITE LOW KIDNEY FUNCTION

NORMAL HOMOCYSTEINE LEVELS IN WELL‐FUNCTIONING OLDEST‐OLD INDIVIDUALS DESPITE LOW KIDNEY FUNCTION

Inappropriately low angiotensin II generation: a factor determining reduced kidney function and survival in patients with decompensated cirrhosis

Background/ Aims : Angiotensin II contributes to the post-glomerular arteriolar vasoconstriction which maintains the glomerular filtration rate (GFR) in renal hypoperfusion. To explore whether depressed angiotensin II generation, due to reduced angiotensinogen production or low angiotensin-converting enzyme (ACE) levels, could impair kidney function in advanced cirrhosis. Methods : We studied and prospectively followed up 21 diuretic-free ascitic cirrhotic patients, through these determinations: plasma levels of active renin (AR), renin activity (PRA), angiotensin II, ACE and aldosterone; renal clearances of sodium, inulin and para-aminohippurate; antipyrine clearance. Fifteen healthy subjects were also studied. Results : GFR distribution was bimodal, 10 patients had low GFR values (l-GFR group) and 11 had normal-GFR values (n-GFR group) (below and above 105 ml/min per 1.73 m 2 body surface area). Antipyrine clearance and Child-Pugh score did not differ in the two patient groups. l-GFR group had higher AR and PRA values, lower ACE levels and a significantly higher AR/Angiotensin II ratio than n-GFR group (all P<0.01). All 21 patients showed increased values of the AR/PRA ratio, i.e. subnormal angiotensinogen levels ( P<0.03). The 18-month survival rates of l-GFR and n-GFR groups were 20 and 81% ( P<0.02). Conclusions : Low-GFR cirrhotic patients had a worse survival rate associated with more severe contraction of the effective arterial blood volume, higher AR/Angiotensin II ratio and lower ACE levels.

Antioxidant Effect of Zinc on Acute Renal Failure Induced by Ischemia-Reperfusion Injury in Rats

Zinc may have an antioxidant effect mediated by induction of metallothionein. Based on the assumption that metallothionein can scavenge oxygen free radicals, we examined whether zinc administration prior to renal ischemia would improve renal dysfunction caused by ischemia-reperfusion injury in rats. Wistar rats weighing 265 g were treated with an intraperitoneal injection of 20 mg/kg zinc 24 h prior to the renal ischemia-reperfusion procedure, which was achieved by a 30-min clamping of the bilateral renal vessels and subsequent 90-min reperfusion. Thirty-minute renal clearance tests were performed before and after renal ischemia in zinc- (n = 11) and saline-treated (n = 8) rats. Thiobarbituric acid reactive substance, conjugated diene, and metallothionein levels in the renal tissues were also determined. Sham-operated rats (n = 5 in each treatment) served as control for the ischemia-reperfusion rats. Ischemia-reperfusion resulted in significantly lower glomerular filtration rate values and marked increases in tissue concentrations of thiobarbituric acid reactive substance and conjugated diene compared with sham-operation. Zinc administration improved the reduced glomerular filtration rate values seen after the ischemia-reperfusion procedure, but not to the extent of pre-ischemic levels. Zinc pretreatment significantly reduced the increased levels of thiobarbituric acid reactive substance and conjugated diene during ischemia-reperfusion and increased metallothionein levels compared with saline injection. These findings suggest that zinc has an antioxidant effect mediated through the induction of metallothionein, but appears only to have a minor protective effect on renal function induced by renal ischemia-reperfusion injury.

Extrarenal plasma clearance of iohexol and other markers of normal and reduced glomerular filtration rate.

T he ~clearance of markers of glomerular filtration rate (GFR) from plasma is used to determine tile GFR of the two kidneys in cooperation. The ideal GFR marker should have glomemlar, filtration as the only mechanism clearing it from plasma. The ideal GFR marker does not exist today, as all markers have some extrarenal clearance. The demands on the presently used GFR markers are maximal clearance by glomerular filtration, minimal excretion and reabsorption by the renal tubuli, and minimal extrarenal clearance. Two techniques used to determine GFR are the renal plasma clearance technique (often called simply renal clearance) and the total plasma clearance technique (often called simply plasma clearance). Both clearance techniques require plasma samples of tile GFR marker and use tile marker concentrat ions in those samples and various pharmacokinetic models to make mathematical formulas that describe tile plasma concentrat ion of the marker over time. The mathematical formulas then are used to calculate an area under the plasma concentrat ion curve (the vertical axis is plasma concentration of marker and the horizontal axis is time). The renal clearance technique gives tile GFR after dividing the amount of marker collected in the urine in a given period by tile area under the curve in tile same period. The major drawback of renal clearance is its sensitivity to inaccurate urine sampling of the marker and the occurrence of residual urine in the bladder. This may give false low or false high GFR values. The plasma clearance technique gives GFR after dividing the dose of the marker by tile area under the curve in the period from time of injection to infinity. The major drawback of plasma clearance is its ignorance of tile extrarenal excretion of the marker, which produces false high GFR values. We sought to improve the determination of GFR with plasma clearance techniques by investigating the extrarenal clearance of tile marker at different levels of GFR. If the extrarenal clearance of a GFR marker in a species is fairly constant at different levels of GFR, this known extrarenal clearance in that species could be subtracted from tile plasma clearance of the marker to get clearance values closer to tile true GFR. If the results show that the extrarenal This work was supported by the Swedish State (Medical Research Council) and by Nycomed Imaging (Oslo, Norway). From the Departments of 1Diagnostic Radiology, 2Nephrology, and 3Radiophysics, Malm0 University Hospital, Matm0, Sweden. Address reprint requests to T. Alm~n, MD, PhD, Department of Diagnostic Radiology, Maim0 University Hospital, S-205 02 Maim0, Sweden.

Measurement of glomerular filtration rate in adults: accuracy of five single‐sample plasma clearance methods

After an intravenous injection of a tracer that is removed from the body solely by filtration in the kidneys, the glomerular filtration rate (GFR) can be determined from its plasma clearance. The method requires a great number of blood samples but collection of urine is not needed. In the present investigation the total plasma clearance of 51Cr-EDTA (ethylenediaminetetra-acetate) was assessed from 13 blood samples taken 5-300 min post-injection in 44 adult patients with GFR greater than 15 ml min-1. In 34 of these patients the plasma clearance of 99Tcm-DTPA (diethylenetriaminepenta-acetate) was determined simultaneously. Using these clearance values as reference the accuracy of six simplified methods were studied: five single-sample methods and one five-sample method. The standard error of estimate (SEE) of the single-sample methods ranged from 4.2 to 7.5 ml min-1 using EDTA, and from 3.8 to 6.3 ml min-1 using DTPA. SEE of the five-samples method was 3.0 ml min-1 (EDTA) and 3.1 ml min-1 (DTPA). The single-sample methods given by Christensen & Groth (1986) and by Tauxe (1986) are recommended for daily use, as SEE was small even at low GFR values. In patients with GFR less than 80 ml min-1, in whom a highly accurate determination is needed, a multiple samples method is recommended, e.g., Brøchner-Mortensen (1972).

Decreased renal perfusion after correction of experimental coarctation.

Hemodynamical changes in coarctation were studied with an experimental model. Coarctation of the thoracic aorta was induced in seven puppies at the age of 8 wk. After a 7-month follow-up period a corrective operation with a venous patch was performed. Two dogs were lost a few hours after the correction operation. The remaining five dogs were followed for 12 months postoperatively. Renal perfusion was measured with a 133Xenon washout method just prior to the operation, 1 h, 6 and 12 months postoperatively. The glomerular filtration rate was measured using the 51Cr-EDTA method 1 wk before the operation, 3 wk, 2, 6, and 12 months after it. Six healthy adult dogs were used as controls for glomerular filtration rate measurements. Peripheral renin activity was measured at operation, just before the correction of aortic coarctation, 1/2, 1 h, 1, 3, 7 days, 2 and 6 months after the correction operation. Renal perfusion decreased significantly (p less than 0.05) immediately after the correction operation and rose again during the follow-up. Peripheral renin activity rose significantly (p less than 0.01) from the preoperative values and was at its greatest 1 day after the operation. Later on, peripheral renin activity values returned to normal. Coarctated dogs had significantly (p less than 0.01) lower glomerular filtration rate values than controls in each measurement except at the 2 months postoperative measurement. These results support decreased renal perfusion with resultant increased peripheral renin activity as part of the pathomechanism of the paradoxical hypertension observed after correction of coarctation.