Conventional Renal Function Tests Research Articles

Noninvasive measurement of 13Carbon turnover for evaluation of porcine renal grafts during ex vivo machine perfusion

BackgroundKidney transplantation suffers from a shortage of donor organs. Despite this, a lot of grafts are discarded due to inadequate quality. As many kidneys are afflicted by transient filtration failure early after preservation, classical renal function tests are not applicable to differentiate between prospective recovery or continuing deficit of renal function.MethodsUsing normothermic machine perfusion as a platform for pre-implantation evaluation of the graft, we present a novel evaluative approach based on the metabolic turnover of 13C-acetate during isolated perfusion. After injection of the tracer, 13CO2 as a metabolic end-product can be quantified by high-precision laser-based spectroscopy in the gas outflow of the oxygenator. Three groups of porcine kidneys with graduated ischemic injury were investigated.ResultsThis quantitative approach is able to discriminate acceptable quality kidneys, most likely to recover within days from poor kidney grafts that are unlikely to regain notable glomerular function with high discriminatory power (area under the ROC curve 0.91; P < 0.001 By contrast, conventional renal function tests are rather ineffective under these circumstances.ConclusionsThis assessment method offers the potential to quantitatively assess donor kidney quality using a measurable output, salvaging donors that would otherwise have been discarded.

Evaluation of conventional renal function tests in β-thalassemia major patients in Nineveh province

β-thalassemia is an inherited anemia, caused by impaired β-globin chain synthesis. The disease leads to serious health problems unless treated by regular blood transfusion and iron chelating therapy. However, complications from continuous therapy may arise due to iron overload and toxicity of iron chelating therapy, it may affects many organs in the body including the renal system. The present study was directed to study the changes in conventional renal function tests that may occur in β-thalassemia patients. The present study consisted of two groups of β-thalassemia patients; group A, 40 transfusion dependent β-thalassemia patients receiving only regular blood transfusion, age ranged 1-4 years; Group B, 40 transfusion dependent β- thalassemia patients receiving regular blood transfusion and deferroxamine chelation therapy, age ranged 4-20 years old. In addition to a control group C, 40 subjects, age ranged 1-20 years. Blood samples were collected and serum was separated for measurement of creatinine, urea, and ferritin. Urine samples were also collected for measurement of microalbuminuria. There was a significant decrease in serum creatinine, and a significant increase in serum urea in group B when compared with their control (P≤0.01). In addition, there was a significant increase in serum ferritin in groups A and B when compared with their controls (P≤0.01). On the other hand, there were no significant changes in microalbuminuria between groups A and B when compared with their controls. The results of the present study showed no deterioration in renal functions in β-thalassemia patients in both groups A and B regarding serum creatinine and urea in addition to microalbuminuria, although, subclinical alteration in renal functions could be expected in those patients, so that measurement of other early markers of renal dysfunction is occasionally recommended.

Renal protective effects of dexmedetomidine in patients undergoing cardiac surgery using cardiopulmonary bypass

Background Cardiac surgery-associated acute kidney injury (CSA-AKI) is a serious complication that increases morbidity and mortality rates. Early detection and prevention of this complication is very important. A novel biomarker, neutrophil gelatinase-associated lipocalin (NGAL), can play an important role in the early diagnosis of acute kidney injury (AKI). Recent studies on the favourable effects of dexmedetomidine (DEX) on renal functions have been published. Objective To evaluate the potential protective effects of DEX against the occurrence of AKI, in patients undergoing cardiac surgeries using cardiopulmonary bypass (CPB), whether coronary artery bypass grafting or valvular surgery, regarding urine output (UOP), serum creatinine, creatinine clearance, and urinary NGAL. Patients and methods A prospective randomized double-blind study was conducted, in which 60 adult patients of both sexes, with Cleveland Clinic Score of 0–5, scheduled for elective cardiac surgeries were included. Patients were randomly allocated into two groups: DEX group, where patients received 0.4 µg/kg/h infusion after weaning from CPB, and placebo group (non-DEX) group, where patients received normal saline in the same volume (ml) and rate (ml/h). The primary end point was the incidence of AKI defined by the AKIN criteria of serum creatinine. Urinary NGAL was assessed immediately after anaesthetic induction, and 4 and 24 h postoperatively. Blood urea, serum creatinine, and creatinine clearance were measured just before anaesthetic induction, and every 12 h for 3 days postoperatively. Moreover, UOP was measured intraoperatively and every 4 h for 72 h after surgery. Postoperative pain was assessed using the visual analogue scale every 4 h for the first postoperative day. Results The severity of AKI in DEX group was confined to stage ‘1’, except for one patient, whereas in non-DEX group, five patients developed stage ‘2’, with a significant higher incidence than in DEX group. Urinary NGAL was significantly lower in DEX group, in addition to the significantly higher values in UOP during the postoperative period. Other conventional renal function tests showed comparable results between both groups. A shorter time to extubation and a lower visual analogue scale pain score were accompanying the use of DEX. Conclusion DEX proved to be effective in the prophylaxis against AKI in this cohort of relatively low-risk elective cardiac patients in terms of NGAL values, but did not affect conventional renal functions in terms of serum creatinine, and creatinine clearance, and it was associated with an increase in urinary output. DEX also helped in earlier extubation, and shorter duration of mechanical ventilation. In addition, DEX proved to have potent analgesic properties.

Effects of N-acetyl cysteine on renal functions evaluated by blood neutrophil gelatinase-associated lipocalin levels in geriatric patients undergoing coronary artery bypass grafting.

Objective:Recent conflicting studies on the renal effects of N-acetyl cysteine (NAC) after cardiac surgery have been published. The aim of this study was to evaluate the renal effects of NAC using neutrophil gelatinase-associated lipocalin (NGAL) blood levels in elderly patients undergoing coronary artery bypass grafting (CABG).Methods:This randomized, double-blinded, placebo-controlled study was conducted among geriatric patients (>65 years) scheduled to undergo CABG. A total of 60 consecutive patients were randomly assigned to 2 groups. The first group received I.V. NAC (n=30) and the second group received placebo (n=30) at induction of anesthesia and then for 20 h. NGAL values were determined and conventional renal function tests were performed. Statistical analysis was performed using SPSS 17.0 (IL, Chicago, USA). A p value of <0.05 was considered statistically significantResults:Plasma creatinine levels at 24 h postoperatively were significantly higher in the placebo group than in the NAC group (1.41±0.63 vs. 1.13±0.35; p<0.05). The mean serum NGAL levels at 3 h postoperatively were higher in the placebo group than in the NAC group (104.94±30.51 vs. 87.82±25.18; p<0.05). NGAL levels were similar between the groups at all other measurement time points. Plasma creatinine levels of ≥1.5 mg/dL or >25% of the baseline value at any time during the study period were observed in 27% of patients in the NAC group and 37% of patients in the placebo group; the difference was statistically significant (p<0.05).Conclusion:In the present study, we found that I.V. NAC infusion in elderly patients undergoing CABG reduced the incidence of acute kidney injury as determined by blood NGAL and creatinine levels.

The dose-related effects of dexmedetomidine on renal functions and serum neutrophil gelatinase-associated lipocalin values after coronary artery bypass grafting: a randomized, triple-blind, placebo-controlled study.

Acute kidney failure after coronary artery bypass grafting (CABG) is a serious complication that increases morbidity and mortality rates. Early detection and prevention of this complication are very important. A novel biomarker named neutrophil gelatinase-associated lipocalin (NGAL) can play an important role in early diagnosis of acute kidney injury. Recent studies on the favourable effects of Dexmedetomidine on cardiac surgery have been published. The aim of this study is to investigate whether there is a dose-dependent positive effect of Dexmedetomidine on neutrophil gelatinase-associated lipocalin levels and renal functions when used after CABG. Our randomized, triple-blinded, placebo-controlled study was conducted among 295 patients scheduled for CABG surgery between August 2009 and March 2011 in a tertiary cardiac and vascular surgery clinic. A total of 90 consecutive patients who met inclusion criteria were randomized and divided into three groups. The first group received a placebo. The second and the third groups received 4 and 8 µg/cc concentration of the Dexmedetomidine infusion, respectively. Infusion rates were regulated to obtain sedation with a Ramsey sedation score of 2 or 3. Patients were regrouped according to the total Dexmedetomidine dose. Statistical analyses of variables including serum neutrophil gelatinase-associated lipocalin values and conventional renal function tests were made for all six possibilities before the blind was broken. Results of conventional renal function tests were not significantly different. However, neutrophil gelatinase-associated lipocalin levels for the first postoperative day for placebo, low-dose and high-dose Dexmedetomidine groups were 176.8 ± 145.9, 97.7 ± 63.4 and 67.3 ± 10.9 ng/ml, respectively. These values were significantly different among the groups (P <0.001). In our study, we found that Dexmedetomidine infusion for sedation after CABG under cardiopulmonary bypass can be useful in the prevention of kidney injury. Conventional renal function tests, including blood urea nitrogen, serum creatinine, urine output and creatinine clearance rate measurements typically may not detect the development of acute kidney dysfunction in the first 48-h postoperative period. Differences were detected in renal function in the early postoperative period and the development of acute kidney injury, as determined by measurements of blood NGAL levels, was significant and dose-dependent.

Effect of Gum Arabic on Oxidative Stress and Inflammation in Adenine–Induced Chronic Renal Failure in Rats

Inflammation and oxidative stress are known to be involved in the pathogenesis of chronic kidney disease in humans, and in chronic renal failure (CRF) in rats. The aim of this work was to study the role of inflammation and oxidative stress in adenine-induced CRF and the effect thereon of the purported nephroprotective agent gum arabic (GA). Rats were divided into four groups and treated for 4 weeks as follows: control, adenine in feed (0.75%, w/w), GA in drinking water (15%, w/v) and adenine+GA, as before. Urine, blood and kidneys were collected from the rats at the end of the treatment for analysis of conventional renal function tests (plasma creatinine and urea concentration). In addition, the concentrations of the pro-inflammatory cytokine TNF-α and the oxidative stress markers glutathione and superoxide dismutase, renal apoptosis, superoxide formation and DNA double strand break frequency, detected by immunohistochemistry for γ-H2AX, were measured. Adenine significantly increased the concentrations of urea and creatinine in plasma, significantly decreased the creatinine clearance and induced significant increases in the concentration of the measured inflammatory mediators. Further, it caused oxidative stress and DNA damage. Treatment with GA significantly ameliorated these actions. The mechanism of the reported salutary effect of GA in adenine-induced CRF is associated with mitigation of the adenine-induced inflammation and generation of free radicals.

Effect of gum Arabic on oxidative stress and inflammation in adenine–induced chronic renal failure in rats

Inflammation and oxidative stress are known to be involved in the pathogenesis of chronic kidney disease in humans, and in surgically‐induced chronic renal failure (CRF) in rats. Evidence for the involvement of these processes in adenine‐induced CRF in rats is lacking. The aim of this work was to study the role of inflammation and oxidative stress in adenine‐induced CRF, and the effect thereon of the purported nephroprotective agent gum arabic (GA). Rats were divided into four groups and treated for 4 weeks as follows: control, adenine in the feed (0.75%, w/w), GA in drinking water (15%,w/v) and adenine + GA, as before. Urine, blood and kidneys were collected from the rats at the end of the treatment for analysis of conventional renal function tests (plasma creatinine and urea concentration and urinary NAG activity). In addition, the concentrations of several pro‐inflammatory cytokines and indices of oxidative stress, renal apoptosis, superoxide formation and DNA double strand break frequency detected with immunohistochemistry for γ‐H2AX were also conducted in the kidney tissue, plasma and urine. Adenine (0.75% in the feed for 4 weeks) caused significant increases (P &lt; 0.001) in the concentrations of urea and creatinine in plasma, significantly decreased the creatinine clearance (P &lt; 0.01) and induced significant increases in the concentration of the measured inflammatory mediators. Treatment with GA significantly ameliorated these actions, suggesting that the mechanism of the reported salutary effect of GA in adenine‐induced CRF is associated with mitigation of the adenine‐induced inflammation and generation of free radicals.

Early and quantitative detection of cisplatin-induced nephrotoxicity by measurement of plasma PSP (phenolsulfonphthalein) half-life in rats.

Renal function following cisplatin injection in rats was assessed by measuring the half-life of plasma PSP. Changes in BUN, creatinine, plasma PSP half-life and urinary N-acetyl-beta-D-glucosaminidase (NAG) levels were determined in rats treated with 6.5 mg/kg i.v. of cisplatin. The highest values of BUN and creatinine were both observed on day 5. Half-life of plasma PSP was significantly prolonged on days 2 through 5 and reached a peak value on day 3. A significant increase in urinary NAG levels appeared on day 2 and the peak value was demonstrated on day 3. BUN, creatinine and plasma PSP half-life were also determined on days 3 and 5 following several doses of i.v. cisplatin. A dose-related increase in plasma PSP half-life was observed on day 3, while dose-related increases in BUN and creatinine levels were found on day 5. The evaluation of cisplatin-induced nephrotoxicity by the plasma PSP test was clearly superior for early detection compared with conventional renal function tests using BUN and creatinine.

Arterial embolization in patients with grade-4 blunt renal trauma: evaluation of the glomerular filtration rates by dynamic scintigraphy with 99mTechnetium-diethylene triamine pentacetic acid

BackgroundHigh-grade blunt renal trauma has been treated by arterial embolization (AE). However, it is unknown whether AE preserves renal function, because conventional renal function tests reflect total renal function and not the function of the injured kidney alone. Dynamic scintigraphy can assess differential renal function.MethodsWe performed AE in 17 patients with grade-4 blunt renal trauma and determined their serum creatinine (sCr) level and glomerular filtration rate (GFR; estimated by dynamic scintigraphy) after 3 months. In 4 patients with low GFR of the injured kidney (<20 ml·min-1·1.73 m-2), the GFR and sCr were measured again at 6 months. Data are presented as median and interquartile range (25th, 75th percentile).ResultsThe median GFR of the injured kidney, total GFR, and median sCr at 3 months were 29.3 (23.7, 35.3) and 96.8 (79.1, 102.6) ml·min-1·1.73 m-2 and 0.6 (0.5, 0.7) mg/dl, respectively. In the patients with low GFR (ml·min-1·1.73 m-2), the median GFR of the injured kidney, total GFR, and median sCr (mg/dl) were 16.2 (15.7, 16.3), 68.7 (61.1, 71.6), and 0.7 (0.7, 0.9), respectively, at 3 months and 34.5 (29.2, 37.0), 90.9 (79.1, 98.8), and 0.7 (0.7, 0.8), respectively, at 6 months.ConclusionsThe function of the injured kidney was preserved in all patients, indicating the efficacy of AE for the treatment of grade-4 blunt renal trauma.

Kidney-specific proteins: markers for detection of renal dysfunction after cardiac surgery?

After cardiopulmonary bypass, cardiac surgery patients often suffer from renal injury. Clinicians rely on urine output, serum creatinine, and creatinine clearance as routine measures to evaluate renal function. Kidney-specific proteins such as neutrophil gelatinase-associated lipocalin (NGAL), neutral endopeptidase (NEP), retinol-binding protein (RBP), alphal-microglobulin, N-acetyl-beta-D-glucosaminidase or gluthatione-S-transferases (GSTs) have been studied to define new measures to detect even subclinical or transient compromised renal integrity after cardiac surgery. It has been shown that kidney-specific proteins may be a useful tool for detecting impaired renal function in this situation, and may be superior to conventional renal function tests. Large controlled trials, however, will be necessary to determine the predictive value of kidney-specific proteins.

Blood pressure relates to sodium taste sensitivity and discrimination in adolescents.

To investigate salt perception and discrimination and their possible association with blood pressure (BP), 72 healthy adolescents (42 boys) aged 9-21 years (mean 16.1 years) were studied. BP was measured with a standardized technique. Anthropometric measurement and conventional renal function tests were performed. Sensitivity tests to recognize the presence of salt when given simultaneously distilled/deionized water and a low sodium concentration water solution, and discrimination tests consisting of six graded samples of different saline solutions presented in randomized order were used to assess individual gustatory sensitivity. Average systolic BP values were 113.2+/-1.6 mmHg in boys and 109.6+/-1.9 mmHg in girls. Mean threshold level for salt sensitivity was 4.55+/-0.6 mmol/l. Systolic BP and salt sensitivity showed a significant correlation ( r=-0.33, P<0.01) even when adjusting for weight. Discrimination score was correlated with salt sensitivity ( r=0.27, P<0.05). There is a significant association between gustatory perception and BP in Spain adolescents, although a real cause-effect relationship has not been established.

犬の尿中酵素活性測定について

In a dog, gentamicin (10mg/kg) was given every 8 hours for 9 days to produce experimental renal failure. Then urinalysis showed an increase in urine volume, a decrease in urinary specific gravirty, proteinuria, glucosuria, celluria and enzymuria. Elevation in the activities of the urinary enzymes preceded a rise in levels of creatinine (Cr) and BUN in the serum. Activities of serum Cr rose by day 10 and of BUN by day 14. Urinary LDH, γ-GTP, NAG and ALP began to rise steadily by day 7 and increased rapidly after that. Urinary LAP rose slightly by day 12 and rapidly after that. Urinary LDH5 increased with a rapid rise of total urinary LDH activity. Renal biopsy specimens on days 5 and 9 were examined histologically, showing granular degeneration of the proximal tubules. Necropsy was made on day 16. The renal lesions were characterized by hydropic degeneration and necrotic changes in the proximal tubules and occasional interstitial infiltration of macrophages. Accordingly, it was suggested that assays of urinary enzymes might be more sensitive indicators of renal damage than conventional renal function tests in the small animal practice.

Detection of renal tubular lesions after abdominal aortography and selective renal arteriography by quantitative measurements of brush-border enzymes in the urine.

Quantitative determination of brush-border enzyme excretion in the 24-hour urine is a much more sensitive index of renal tubular damage after aortography and selective renal arteriography than the conventional renal function tests such as serum creatinine and clearance determinations. Among the five brush-border enzymes which we investigated, alkaline phosphatase (AP) was the most sensitive diagnostic pointer. In 90% of hypertensive patients without detectable pre-existing renal parenchymal damage, abnormal levels of AP excretion in the urine were found on the same day as or on the day after the intra-arterial injection of contrast medium. Measurement of other brush-border enzymes does not provide any further diagnostic information. Provided there is no pre-existing renal parenchymal damage, the lesion caused by the contrast medium is transient and is usually reversed within 48 h. For the early detection of tubular lesions caused by tri-iodinated benzoic acid derivatives, AP excretion in the 24-hour urine should be measured at least twice--on the day of the contrast medium injection and on the following day.

QUANTITATIVE EVALUATION OF RENAL FUNCTION USING RENOCARDIOCYSTOGRAM : MEASUREMENT OF RENAL FUNCTION BY A HALF DECREASING TIME COUNTING METHOD

The authors tried to measure renal function quantitatively by an external counting method using131I-Hippuran Renocardiocystogram. For this purpose, we made a system which automatically calculate and record the half decreasing time (T 1/2) of I-Hippuran concentration in blood. Then this external counting method was assessed with 655 cases of various urinary lesions.As the result, with the patients having no urinary retention, a good correlation was found between P.S.P. (15') and T 1/2 ; (r=0.93), while the correlation was relatively low with the patients having urine retention by various lesions. This fact shows that the external counting method is more reliable than the conventional renal function tests which need urine collection.Conclusion : This half decreasing time calculating method with external counting, which requires a patient minimum load, is not only simple to handle but also reliable to evaluate renal function.

Prognostic significance of DNA-binding capacity patterns in patients with lupus nephritis.

The time course of DNA binding capacity (DNA-bc) was found to correlate with the clinical course in a group of 21 patients who had biopsy-proven lupus glomerulonephritis and were treated with immunosuppressive agents. Eight patients showed a sequential DNA-bc pattern in which a high titre of anti-DNA antibody was present for a prolonged period of time all having an unfavourable clinical course. Persistently high values of DNA-bc preceded by as much as 10 months evidence of renal deterioration obtained by conventional renal function tests. Thirteen patients showed a low titre of anti-DNA antibody throughout most of their course, 12 having a favourable outcome. An initially high value of DNA-bc had no prognostic significance. These results suggest that the persistence of a high titre of anti-DNA antibody in patients with lupus glomerulonephritis is a poor prognostic sign.