Low serum urea level in dehydrated patients with central diabetes insipidus.

Dehydrated patients usually present with an elevated serum urea level, owing in part to increased renal reabsorption of urea mediated by antidiuretic hormone (ADH). We carried out a study to examine whether, during dehydration, the variations in the serum urea level could discriminate patients with central diabetes insipidus (CDI) from those with dehydration not due to CDI. We studied retrospectively 27 episodes of dehydration in 23 patients with CDI and 14 episodes in 14 patients without CDI. The mean serum urea level was 2.9 mmol/L in the CDI group and 15.4 mmol/L in the patients without CDI (p less than 0.001); the mean serum sodium level was 155 mmol/L in both groups. All the patients with CDI had a sodium/urea ratio greater than 24.2, whereas the ratio was less than 21.7 in all the patients without CDI. In the patients with CDI a positive correlation was found between the magnitude of diuresis and the percentage decrease in the serum urea level compared with the level before dehydration (p less than 0.001). In the patients with CDI the serum urea level returned to the level before dehydration after the administration of vasopressin; a striking increase in the clearance of urea, which exceeded the creatinine clearance, was observed during dehydration in the three patients in whom clearance studies were done. The results suggest that serum urea values can be used to distinguish patients dehydrated because of CDI from those with hypertonic dehydration but without ADH deficiency and that during dehydration the net reabsorption of urea is dependent on the renal action of ADH.     

Comparison of cell-mediated lympholysis and mixed lymphocyte culture in the immunologic evaluation for renal transplantation

We investigated the relationship between both pre-transplant cell-mediated lympholysis assay (CML) and mixed lymphocyte culture (MLC) and transplant outcome (graft function and survival) in 33 living, related donor renal transplants performed during the past 5 yr. Both assays were excellent predictors of transplant outcome. A positive CML assay was correlated with the occurrence of early acute rejection episodes (p less than 0.005), shortened time to graft dysfunction (serum creatinine greater than 1.5 mg/dl) (p less than 0.001), and poor long-term graft survival (p = 0.07). Similarly, a positive MLC was correlated with acute rejection episodes (p less than 0.005), graft dysfunction (p = 0.001), and poor graft survival (p less than 0.01). To determine the relative prognostic significance of the CML and MLC assays, we compared the correlation of each of them with the occurrence of acute rejection episodes. Under a logistic model of probability, the CML and MLC assays were equally predictive of an early acute rejection episode (p less than 0.01); however, the combination of CML and MLC together improved the accuracy of the prediction of an acute rejection episode by 50%. These results indicate that the CML and MLC assays are independent predictors of transplant outcome and that both tests should be an integral part of the immunologic evaluation of prospective living, related donors for renal transplantation.     

Serum metabonomics study of chronic renal failure by ultra performance liquid chromatography coupled with Q-TOF mass spectrometry

A metabonomics technique based on ultra-performance liquid chromatography (UPLC) coupled with Q-TOF mass spectrometry was employed to investigate the sera from 32 patients with chronic renal failure (CRF) without renal replacement therapy and 30 healthy volunteers in order to find potential disease biomarkers and reveal its pathophysiological changes. After data acquisition Waters MarkerLynx software was used to report retention time and m/z pairs for each metabolite peak, these data were exported to an excel table, then handled by using multivariate analysis and the statistical analysis in the SIMCA-P and the SPSS softwares to obtain potential biomarkers which were further identified by MS/MS. Seven potential biomarkers, creatinine, tryptophan, phenylalanine, kynurenine and three lysophosphatidylcholines, were identified. The results suggest that CRF can lead to the increase of reservation of creatinine in the body, and the abnormal metabolism of the two essential amino acids and lysophosphatidylcholines. It has indicated that metabonomics will be a powerful tool in the clinic research.     

Effects of Renal Function on Plasma Digoxin Levels in Elderly Ambulant Patients in Domiciliary Practice

An investigation into the relations between the daily dose of digoxin, drug regimen, serum digoxin concentration, and creatinine and digoxin clearance was carried out in a group of elderly ambulant patients in domiciliary practice. Moderate to severe impairment of renal function was found both in patients taking digoxin and in elderly control subjects. Plasma digoxin levels were not related to blood urea concentrations or creatinine clearance. Digoxin clearance was less than creatinine clearance. Now that plasma digoxin levels can be measured relatively easily their estimation should become part of clinical practice.     

PTH、BUN及CRe联合检测对早期肾功能衰竭的诊断价值

目的:探讨甲状旁腺激素、尿素氮及肌酐联合检测在肾功能衰竭患者早期诊断中的临床意义。方法:选取2012年1月-2013年8月在我院接受治疗的80例肾功能衰竭患者作为研究对象,另选同期体检正常人40例为对照组,选用我院全自动化学分析仪器及电化学发光免疫分析测量仪器检测患者血清中甲状胖腺激素、尿素氮及肌酐水平。结果:与对照组患者比较,观察组患者血清样本中甲状旁腺激素水平、尿素氮水平与肌酐水平呈显著增高趋势,有统计学意义(P0.05)。肾功能衰竭患者在其代偿期血清内三项水平呈显著增高趋势,而在氮质血症期间,血清内三项要素水平升高现象更为显著,而在尿毒症期间,对比氮质血症期间同样有其上升的表现,突出表现为显著的增高态势。结论:在临床诊断中,可将血清样本中甲状旁腺激素水平作为判定其肾功能衰竭严重程度的关键指标。     

Application of creatinine-sensitive biosensor for hemodialysis control

The highly sensitive and selective potentiometric biosensor for creatinine determination has been developed by us earlier. In it, pH-sensitive field effect transistors were used as transducer and immobilized creatinine deiminase (EC 3.5.4.21)--as a biosensitive element. In the work presented, we optimized this biosensor for creatinine analysis in real samples of dialysate in patients with renal failure. The optimized version of biosensor was applied for on-line monitoring of the level of creatinine in the patient's dialysate fluid in the course of dialysis session. High correlation between the biosensor analysis and traditional Jaffe method was demonstrated.     

Prevalence of advanced renal failure in Northern Ireland.

OBJECTIVE--To determine the prevalence of advanced chronic renal failure in Northern Ireland as part of an assessment by the Renal Association of the level of service provision for treatment of such patients. DESIGN--Prospective notification of patients reaching a defined level of advanced chronic renal failure (serum creatinine concentration greater than or equal to 500 mumol/l or blood urea concentration greater than or equal to 25 mmol/l) within one year and follow up for at least three, and, at most, four years after notification. SETTING--Northern Ireland. PATIENTS--122 Patients with a serum creatinine or blood urea concentration higher than the defined level newly detected from 1 March 1985 to 28 February 1986. MAIN OUTCOME MEASURE--Survival after notification. RESULTS--77 Patients of all ages/million population/year had advanced chronic renal failure compared with 67/million/year between the ages of 5 and 80 found in an earlier study of the same population. 62% Of the patients were older than 50 years. Seventeen (14%) of the patients either required dialysis or died within one month of notification, 51 (42%) survived for at least three months, and 23 (19%) for one year or longer. Three patients, all of whom were attending a renal clinic, survived for periods of 43, 45, and 46 months respectively without renal replacement treatment. CONCLUSIONS--The increased number of new patients disclosed in this survey compared with the earlier survey is mainly owing to an increased number of older patients. Such patients often have disabilities other than renal failure, are less likely to be capable of self treatment, may develop complications more often and require more frequent hospital admissions, and may not be suitable for transplantation and consequently have considerable resource implications for the NHS.     

Plasma creatinine and urea: creatinine ratio in patients with raised plasma urea.

We examined the plasma urea and creatinine concentrations and the ratio between them according to diagnosis in 100 unselected and 31 selected adult hospital patients with a plasma urea concentration greater than or equal to 10 mmol/l (60mg/100ml). We also examined plasma urea and creatinine concentrations in 350 unselected consecutive patients, but found no useful relation between the two values. Congestive heart failure was the most common identifiable cause of a raised plasma urea concentration in the 100 unselected patients (36%). Among these 100 patinets the plasma creatinine concentration was a more useful discriminant between prerenal uraemia and intrinsic renal failure than was the urea:creatinine ratio or the plasma urea concentration. A plasma creatinine concentration greater than 250 mumol/1 (2-8 mg/100ml) indicated intrinsic renal failure with a 90% probability.     

Effect of cimetidine on upper gastrointestinal bleeding after renal transplantation: a prospective study.

In 97 consecutive patients undergoing renal transplantation the incidence of upper gastrointestinal bleeding was registered over 180 days after allocation to treatment with either cimetidine or placebo. Bleeding episodes occurred in 12 patients, 11 of whom were receiving placebo and only one cimetidine (p less than 0.01). All bleeding episodes occurred during the first month after allotransplantation. Treatment with cimetidine did not lead to an increased incidence of rejection of the allograft. It is concluded that cimetidine is effective and safe in protecting against upper gastrointestinal bleeding after renal transplantation.     

Serious renal transplant rejection and adrenal hypofunction after gradual withdrawal of prednisolone two years after transplantation.

Ten patients with stable renal function two years after transplantation had their sole immunosuppressive treatment (oral prednisolone 10 mg daily) withdrawn by reducing the daily dose by 1 mg at monthly intervals. Plasma prednisolone concentration, cortisol concentration, creatinine clearance, and serum creatinine concentration were measured in all patients, and the adrenal response to corticotrophin was determined in five by measuring plasma cortisol concentrations before and after tetracosactrin injection. No episodes of rejection occurred in patients taking over 7 mg prednisolone daily. Although three patients apparently required only minimal immunosuppressive treatment (less than 5 mg daily) the remainder suffered episodes of rejection at daily doses below 7 mg. There was a tenuous association between rejection and low plasma cortisol concentration, but neither the pattern of plasma prednisolone concentrations nor the response to tetracosactrin were related to episodes of rejection. Reducing the daily dose of oral prednisolone to under 7 mg should not be attempted in patients with renal transplants unless there are extenuating circumstances.     

Protective effect of N-acetylcysteine (NAC) on renal ischemia/reperfusion injury through Nrf2 signaling pathway

Abstract

The aim of this study was to investigate whether N-acetylcysteine (NAC), a known antioxidant, can protect kidney against ischemic injury through regulating Nrf2 signaling pathway. The expression of Nrf2, HO-1 and cleaved caspase 3 were analyzed by Western blot analysis. Apoptosis of renal tubular epithelial cells was assessed by the TUNEL method. Malondialdehyde (MDA) levels were measured by the thiobarbituric acid reaction. Blood serum creatinine and blood urea nitrogen levels were measured with an Olympus automatic multi-analyzer. We found that NAC significantly increased Nrf2 and downstream HO-1 expression. Furthermore, NAC significantly decreased cleaved caspase 3, p53 and renal epithelial tubular cell apoptosis. In addition, NAC reduced the MDA level. These findings suggest that the protective action of NAC on ischemia renal injury is associated closely with Nrf2 signaling pathway.     

Abnormal renal response to twenty-four-hour dehydration and fasting in Nagase analbuminemic rats.

We assessed renal function in fasting adult Nagase analbuminemic rats (NAR). Sodium output in male and female NAR was 68% and 46%, respectively, of the output of age- and sex-matched normal Sprague-Dawley (SD) rats. Potassium excretion was significantly greater in female NAR but there was no difference between male NAR and SD rats. The renal clearances of urea and creatinine were reduced in NAR with corresponding increases in plasma concentrations; however, the urea and creatinine concentrations were not different in plasma samples taken from normally fed and hydrated SD and NAR rats. Exchangeable body sodium and sodium space was significantly larger in normally fed and hydrated NAR than in SD but there were no differences in plasma sodium concentrations or plasma volumes. Although plasma concentrations of albumin in NAR were only about 0.07% of the concentration in SD rats, the renal clearance of albumin in NAR was threefold greater. Kidney weights in NAR were 10 to 16% less than in SD rats but liver weights were 22 to 42% greater. Clearly, renal function was markedly abnormal in Nagase rats during a 24-hour fast.     

Doppler studies in the growth retarded fetus and prediction of neonatal necrotising enterocolitis,haemorrhage, and neonatal morbidity.

In 82 consecutive cases of intrauterine growth retardation managed by established criteria fetal Doppler studies identified 29 fetuses with absence of end diastolic frequencies in the fetal aorta. These same fetuses were significantly more growth retarded (p less than 0.001) and had an earlier gestational age at delivery (p less than 0.001) than those with end diastolic frequencies present. A subgroup of these cases was analysed in more detail to examine the prognostic value of this phenomenon for the neonate. Two groups of neonates of equivalent gestational age and with a birth weight below 2000 g were compared. There were 26 neonates with absent end diastolic frequencies (group 1) and 20 with end diastolic frequencies (group 2) in the fetal aorta. Those in group 1 were more likely to suffer perinatal death (p less than 0.05), necrotising enterocolitis (p less than 0.01), and haemorrhage (p less than 0.05). Only 4 (15%) of the babies in group 1 had an uncomplicated neonatal period compared with 15 (75%) in group 2 (p less than 0.001). The circulatory changes identified in these cases may provide a more sensitive measure of critical fetal compromise than current techniques and thus allow the clinician to deliver the fetus before irreversible tissue damage has occurred.     

Alteration of vascular thromboxane in rats with subtotal renal ablation

To assess the roles of vascular prostaglandins in the hypertension of chronic renal failure, the release of prostacyclin and thromboxane (TX) from aorta was evaluated in male Sprague-Dawley rats, the renal mass of which was reduced by removing one kidney and two-thirds of the contralateral kidney ("5/6 nephrectomy"). Five-sixths nephrectomy was followed by significant rises in serum creatinine to 0.55 +/- 0.03 mg/dl and urea nitrogen to 42.9 +/- 3.8 mg/dl, with a concomitant rise in mean blood pressure from 121.6 +/- 1.6 mmHg to 155.3 +/- 8.4 mmHg. In 5/6 nephrectomized rats, the release of TX A2 from aorta, as measured by its stable metabolite TX B2, increased by 60% (p less than 0.01) and prostacyclin, as measured by its stable metabolite 6-keto-prostaglandin, F1 alpha (6-keto-PG F1 alpha) increased by 51% (p less than 0.05). The amounts of both TX B2 and 6-keto-PG F1 alpha released from aorta were closely related to the height of mean blood pressure. These results suggest that the enhanced vasoconstrictor TX production in the vascular walls may be relevant to hypertension in rats with subtotal renal ablation. The adaptive increase in prostacyclin production in the vascular walls may compensate for the elevation of blood pressure due to chronic renal failure in this animal model.     

Association of plasma manganese levels with chronic renal failure

Manganese (Mn) is an essential trace element involved in the formation of bone and in amino acid, lipid and carbohydrate metabolism. Mn excess may be neurotoxic to humans, affecting specific areas of the central nervous system. However, relatively little is known about its physiological and/or toxicological effects, and very few data are available concerning the role of Mn in chronic renal failure (CRF). This paper describes a 12-month study of the evolution of plasma Mn levels in predialysis patients with CRF and the relationship with energy and macronutrient intake. The participants in this trial were 64 patients with CRF in predialysis and 62 healthy controls. Plasma levels of creatinine, urea, uric acid, total protein and Mn were measured. The glomerular filtration rate (GFR) was calculated using the Cockcroft-Gault index. The CRF patients had higher plasma levels of creatinine, urea, uric acid and Mn and a lower GFR than the controls. Plasma Mn was positively correlated with creatinine, plasma urea and plasma uric acid and was negatively correlated with the GFR and the intake of energy and macronutrients. In conclusion, CRF in predialysis patients is associated with increases in circulating levels of Mn.     

Isolation-induced renal functional changes in rats from four breeders

The investigation of drug-induced nephrotoxicity depends on the adequate estimation of renal function at baseline and upon completion of the study. Typically, this procedure requires housing of the animal in an individual wire-bottom metabolic cage to facilitate complete urine collection. The present study compared the effects of 4 consecutive days of isolation on Sprague-Dawley rats from four breeders: Harlan Sprague-Dawley, Charles River Laboratories, BioLab and TIMCO Breeders. Following 4 days of isolation, weight loss was not significantly different between groups. However, urine flow rate declined significantly (p less than 0.0005) in TIMCO and Charles River breeder rat groups during the study period compared to baseline values and other groups. Serum creatinine levels were 63% greater (p less than 0.01) with a 40% decline in creatinine clearance (p less than 0.0001) after 4 days of isolation in TIMCO rats. Although a 59% decrease in baseline creatinine clearance was found in Charles River rats after 96 hours of isolation (p less than 0.0005), the mean baseline value was 38% greater than other rat groups (p = 0.04). Fractional reabsorption of sodium was 4.4% less (p less than 0.001) in TIMCO rats compared to baseline. Fractional excretion of potassium was highly variable in all rat groups. We conclude that animal isolation was associated with a significant change in renal function in TIMCO rats which was not observed in others. Caution is required to consider the source of the rat, and also duration of isolation, in studies requiring the passive assessment of renal function.     

Effects of chronic hypoxia on kidney function

Renal disfunctions which appear in the chronic respiratory insufficient patient are analysed, as well as the participation of the arterial blood hypoxemia in their genesis. Renal clearances of Na, K, Cl, Ca, Mg and Pi, and those of urea and creatinine, were lower in 36 patients having chronic hypoxemia than in 15 normosemic controls, showing significant statistical differences for Na, K, Cl, Ca and urea. The correlations between the clearances of these substances and the pO2 arterial blood levels had a greater statistical significance than can be established with pCO2 or [H+] levels. Thus, the existence of a causal dependency between renal disfunction and hypoxemia may be deduced.     

Early plasma creatinine values in discordant twins.

It has been suggested that impairment of placental perfusion prior to delivery may manifest in early postnatal increase of creatinine values. We hypothesized that the smaller of a discordant set of twins would have a higher initial plasma creatinine value and decided to measure early plasma creatinine levels in discordant twins in order to evaluate whether this value may serve as an index of impaired placental perfusion. Plasma creatinine, urea nitrogen and blood hematocrit values were simultaneously measured in 35 sets of twins during the first day of life. The sets of twins were divided into 2 groups according to birth weight difference. Thus, 18 sets of discordant twins with birth weight difference greater than 15% comprised the GT group and 17 sets of twins with birth weight difference less than or equal to 15% comprised the LE group. The differences between the values obtained within each group were analyzed using the Wilcoxon Signed Rank test. In the GT group the mean plasma creatinine level of the smaller twins was significantly higher than the level of the larger ones (p = 0.03), but there was no statistically significant difference between values obtained in twins of the LE group. The mean plasma urea level was higher in the larger twins of both groups, however only the difference in the GT group was statistically significant (p = 0.01). The mean hematocrit of the smaller twins was higher in both groups, but only the difference in the LE group was statistically significant (p = 0.02). Generally, there was a negative correlation between gestational age and early creatinine values. These results apparently support the notion that prenatal exposure to impaired placental perfusion may compromise the creatinine clearance of the fetus and result in higher early creatinine values. Since the creatinine values in our growth-retarded twins were within the normal range, no distinguishing line for evidence of a uterine-placental compromise could be drawn. Whether a certain early plasma creatinine value is suggestive or indicative of an intra-uterine hypoxic-ischemic insult, should be determined by documented instances of severe fetal compromise prior to delivery.     

Carvedilol: a beta blocker with antioxidant property protects against gentamicin-induced nephrotoxicity in rats

Gentamicin is an antibiotic effective against gram negative infections, whose clinical use is limited by its nephrotoxicity. Since the pathogenesis of gentamicin-induced nephrotoxicity involves oxygen free radicals, the antioxidant carvedilol may protect against gentamicin-induced renal toxicity. We therefore tested this hypothesis using a rat model of gentamicin nephrotoxicity. Carvedilol (2 mg/kg) was administered intraperitoneally 3 days before and 8 days concurrently with gentamicin (80 mg/kg BW). Estimations of urine creatinine, glucose, blood urea, serum creatinine, plasma and kidney tissue malondialdehyde (MDA) were carried out, after the last dose of gentamicin. Kidneys were also examined for morphological changes. Gentamicin caused marked nephrotoxicity as evidenced by increase in blood urea, serum creatinine and decreased in creatinine clearance. Blood urea and serum creatinine was increased by 883% and 480% respectively with gentamicin compared to control. Carvedilol protected the rats from gentamicin induced nephrotoxicity. Rise in blood urea, serum creatinine and decrease in creatinine clearance was significantly prevented by carvedilol. There was 190% and 377% rise in plasma and kidney tissue MDA with gentamicin. Carvedilol prevented the gentamicin induced rise in both plasma and kidney tissue MDA. Kidney from gentamicin treated rats, histologically showed necrosis and desquamation of tubular epithelial cells in renal cortex, whereas it was very much comparable to control with carvedilol. In conclusion, carvedilol with its antioxidant property protected the rats from gentamicin-induced nephrotoxicity.     

Some characteristics of urea accumulation in the renal cortex tissue of rats and dogs

The urea concentration in the renal cortex ([RC]), liver ([L]) and skeletal muscle ([SM]) of non-diuretic Wistar rats was measured chemically and after an i.m. injection of 14C-urea and was compared with the plasma urea concentration ([P]). [L]/[P] and [SM]/[P] always equalled 1, irrespective of whether they were measured chemically or by means of radioactivity. [RC]/[P] was 2.81, again without any difference between chemical and radioactive measurement. The ratio of the chemically measured urea concentration in the renal cortex and plasma of mongrel dogs was 5.71, i.e. significantly higher than in rats (p less than 0.01). The intrarenal infusion of KCN, iodoacetate and ouabain did not alter it significantly (5.52, p greater than 0.05). Active transport, in whatever form, does not seem to be the cause of the high urea concentration in rat and dog renal cortex.