Effect Of Chronic Renal Failure Research Articles

Putative effect of chronic renal failure on granular convoluted tubule of submandibular gland in male rats: Immunohistochemical and ultrastructural study

ObjectiveThis study aimed to investigate the ultrastructural and immunohistochemical changes in the granular convoluted tubule (GCT) of rodents' submandibular gland (SMG) upon theinduction of chronic renal failure. Material and methodsThirty young adult Sprague-Dawley rats were randomized into three groups: the Control group, rats received no intervention; the Sham group, rats underwent surgical incision without nephrectomy; the Experimental group, rats underwent surgical procedures to induce chronic renal failure. Afterward, SMG was examined for histological and ultrastructural changes and immunohistochemical staining for Renin. ResultsHistologically, the experimental group demonstrated cytoplasmic vacuolization within the seromucous acini and ducts. Several GCTs were proliferating, whereas others exhibited degenerative changes in the form of disturbed cytoplasmic architecture. On the ultrastructural level, both acini and ductal segments showed degenerative changes Interestingly, immunohistochemical examination of the lining cells of GCT and intralobular ducts of the experimental group revealed the presence of Renin. ConclusionRenal failure induced histological, immunohistochemical, and ultrastructural variations within GCTs of SMG.

Hirudin Regulates Vascular Function in Chronic Renal Failure through Modulating Macrophage Polarization

Excessive inflammation is responsible for arteriovenous fistula (AVF) failure, which determines the therapeutic effect of chronic renal failure (CRF). Macrophage polarization is of great significance in the inflammatory response. Hirudin (Hiru) has been reported to possess a definite anti-inflammatory effect. This study is to uncover the impacts of Hiru on classically (M1)/alternatively (M2) macrophage polarization in the CRF rat model and rat vascular smooth muscle cells (VSMCs). After the CRF rat model was administrated with different concentrations of Hiru, blood urea nitrogen (BUN) and serum creatinine (Scr) levels were tested. H&E staining was to detect vascular injury, and IHC assay was to analyze inducible nitric oxide synthase (iNOS) and arginase-1 (Arg-1) expressions in vascular tissues. Levels of inflammatory factors were examined by ELISA. Besides, western blot was to estimate the levels of marker proteins related to macrophage, proliferation, and apoptosis. CCK-8 was to measure cell viability. We discovered that Hiru alleviated renal function injury and vascular injury, exacerbated VSMC hyperplasia, and stimulated the differentiation and activation of M1 macrophage towards M2 macrophage in vivo. Moreover, after treatment with lipopolysaccharide (LPS)/IFN-gamma (IFN-γ), the increased M1/M2 ratio and enhanced levels of inflammatory factors were observed. Furthermore, Hiru boosted the proliferation and ameliorated the inflammatory response and apoptosis of rat VSMCs during the process of coincubation of M1-conditioned medium (CM). Collectively, Hiru played a protective role against vascular injury in CRF directly or through its influence on M1 macrophage polarization and inflammation.

Renal failure suppresses muscle irisin expression, and irisin blunts cortical bone loss in mice.

BackgroundChronic renal failure induces bone mineral disorders and sarcopenia. Skeletal muscle affects other tissues, including bone, by releasing myokines. However, the effects of chronic renal failure on the interactions between muscle and bone remain unclear.MethodsWe investigated the effects of renal failure on bone, muscle, and myokines linking muscle to bone using a mouse 5/6 nephrectomy (Nx) model. Muscle mass and bone mineral density (BMD) were analysed by quantitative computed tomography 8 weeks after Nx.ResultsNephrectomy significantly reduced muscle mass in the whole body (12.1% reduction, P < 0.05), grip strength (10.1% reduction, P < 0.05), and cortical BMD at the femurs of mice (9.5% reduction, P < 0.01) 8 weeks after surgery, but did not affect trabecular BMD at the femurs. Among the myokines linking muscle to bone, Nx reduced the expression of irisin, a proteolytic product of fibronectin type III domain‐containing 5 (Fndc5), in the gastrocnemius muscles of mice (38% reduction, P < 0.01). Nx increased myostatin mRNA levels in the gastrocnemius muscles of mice (54% increase, P < 0.01). In simple regression analyses, cortical BMD, but not trabecular BMD, at the femurs was positively related to Fndc5 mRNA levels in the gastrocnemius muscles of mice (r = 0.651, P < 0.05). The weekly administration of recombinant irisin to mice ameliorated the decrease in cortical BMD, but not muscle mass or grip strength, induced by Nx (6.2% reduction in mice with Nx vs. 3.3% reduction in mice with Nx and irisin treatment, P < 0.05).ConclusionsThe present results demonstrated that renal failure decreases the expression of irisin in the gastrocnemius muscles of mice. Irisin may contribute to cortical bone loss induced by renal failure in mice as a myokine linking muscle to bone.

Effects of caffeic acid phenethyl ester use and inhibition of p42/44 MAP kinase signal pathway on caveolin 1 gene expression and antioxidant system in chronic renal failure model of rats

Effects of Caffeic acid phenethyl ester (CAPE) and/or PD98059 (PD) on the gene expression of Caveolin-1 (CAV1) and reduced glutathione (GSH), malondialdehyde (MDA), copper–zinc superoxide dismutase (CuZn-SOD), and catalase (CAT) enzyme activities were investigated in an experimental chronic renal failure model in rats. Eighty Wistar rats were divided into eight groups for a 28-day study: Control, CsA (Cyclosporine A), CsA-V (CsA solvent), CsA + PD (CsA + PD98059), CsA + PD + CAPE, CsA + CAPE, CAPE-V (CAPE solvent), and PD-V (PD98059 solvent). Serum blood urea nitrogen and creatinine levels, as well as histopathological findings indicated the development of renal failure in the CsA group. Kidney GSH levels decreased while MDA levels, CuZn-SOD, and CAT activities increased significantly in the CsA group compared to control indicating oxidative stress. CAV1 gene expression significantly decreased in the CsA group compared to the control. PD98059 and CAPE applications made positive improvements in the levels of the parameters investigated. PD98059 and CAPE applications in CsA given animals increased GSH and CAV1 gene expressions and decreased CuZn-SOD and CAT levels compared to the CsA group. In conclusion, it was shown that PD98059 and CAPE could attenuate the effects of chronic renal failure, and CAV1 is suggested as a therapeutic target and the inhibition of the p44/42 MAPK pathway may be a new approach for the treatment of renal degenerations.

The Effect of Chronic Renal Failure on the Management and Subsequent Development of Venous Thromboembolism in Geriatric Patients with Isolated Hip Fractures

The Effect of Chronic Renal Failure on the Management and Subsequent Development of Venous Thromboembolism in Geriatric Patients with Isolated Hip Fractures

Effects of Chronic Renal Failure on Surgical Outcomes of Laparoscopic Nephrectomy for Benign Diseases? A Comparative Study

Effects of Chronic Renal Failure on Surgical Outcomes of Laparoscopic Nephrectomy for Benign Diseases? A Comparative Study

Autonomic function test in chronic renal failure patients

Background: Autonomic dysfunction has been recognized as an important contributor to the poor outcome in chronic kidney disease patients. Several studies have reported abnormalities in autonomic function tests in chronic renal failure. Objectives: To study the effect of chronic renal failure on autonomic function tests and to compare the difference in autonomic function test between normal versus chronic renal failure patients, Material and methods: This is a comparative case control study undertaken by me in the Department of physiology, cardiovascular autonomic function tests were performed for Thirty cases of chronic renal failure patients and thirty matched controls of both the genders after obtaining informed written consent and then compared, which include deep breathing test, valsalva maneuver, diastolic pressure response to cold pressor test, response to standing on heart rate and hand grip test. Result: A total of 60 respondent are available for data analysis and the normal healthy subjects values are correlated with the chronic renal failure patients, for valsalva ratio (p=0.0001), deep breathing test (p=0.0003), response to standing in heart rate (p=0.0124) rise in diastolic blood pressure in hand grip test (p=0.001) and rise in diastolic Blood pressure in cold pressor test p=0.001) respectively. Conclusion: This study concludes both parasympathetic and sympathetic dysfunction is seen chronic renal failure patients.

The Effect of Chronic Renal Failure on Thyroid Hormones Specificity Measured fT3 in a Sample of Iraqi Patients

Background: Chronic renal failure (CRF) affects thyroid function in multiple ways, including low circulating thyroid hormone concentration, altered peripheral hormone metabolism, disturbed binding to carrier proteins, possible reduction in tissue thyroid hormone content, and increased iodine store. Objective: To evaluate of thyroid Gland Function in patients with chronic renal failure and an attempt to find a relationship between chronic renal failure and thyroid dysfunctions. Subjects and Methods: A total number of 96 subjects with age range from 15-67 years old (56 males and 40 females) were included in this study. Total number was divided into two groups according to their number Group A. Study group: haemodialysis (HD) consists of 48 patients and Group B. Control group: consists of 48 subjects. T3, T4, TSH, fT3, Urea, Creatinine, Albumin and TSP were measured in each of the two groups. Results: The results revealed statistically significant reduction serum level of tT3 , fT3 more than tT4 in Chronic Renal Failure group in comparison with normal levels in control group while there is no statistically significant difference seen between case and control groups in regard to TSH. Conclusion: There is a decrease serum level of tT3 , tT4 and fT3 but the decreased of tT3 and fT3 more than tT4 in Chronic Renal Failure group in comparison with normal levels in control group.

Quality of life of patients undergoing hemodialysis

Introduction: Chronic Renal Failure (CRF) is a chronic disease, which has a negative impact on the quality of patients’ life. The study of factors affecting the quality of life of these patients is necessary to investigate the impact of the disease in a biological, psychological and social level.Aim: The purpose of this research study was to investigate the satisfaction of patients undergoing chronic hemodialysis and their perceptions of their quality of life.Material and Method: The study sample consisted of patients undergoing chronic hemodialysis at a Dialysis Unit in Athens. The study lasted from January 2016 to March 2016. To measure the health related quality of patients’ life, the Greek version of the questionnaire WHOQOL-BREF of the World Health Organization was used. The completion of the questionnaires was made by the method of the structured interview. A total of 70 questionnaires were completed.Results: According to the study results, most of the patients considered the quality of their life as good (48.6%), while the 8.5% described it as bad or very bad. The lowest satisfaction rates associated with issues of physical health and independence with mean (12.89 ± 2.23) and the highest with social relations (14.68 ± 1.50).Conclusion: The effect of Chronic Renal Failure on the physical, psychological and social background of patients on dialysis is an essential factor in creating a tailor-made holistic treatment program, adjusted to the specific needs of each patient.

The Effect of Chronic Renal Failure on Thyroid Hormones

Chronic renal failure (CRF) affects thyroid function in multiple ways, including low circulating thyroid hormone concentration, altered peripheral hormone metabolism, disturbed binding to carrier proteins, possible reduction in tissue thyroid hormone content, and increased iodine store in thyroid glands.The target of study is to find a relationship between chronic renal failure and thyroid function.In addition, we tried to study the effect of CRF on serum creatinine dependent on the level of thyroid hormones (T3 and T4) and thyroid stimulating hormones(TSH). Forty patients with chronic renal failure (20 male, 20 female) were enrolled in this study in addition to forty healthy individual as control group (20 male, 20 female). The age ranged from (25 -65) years. T4, T3, TSH, urea, uric acid and creatinine were measured in each of the two groups. The results revealed statistically significant reduction in T3 and T4 while there is elevation in TSH, urea,uric acid and creatinine in the patients group compared to the control group.&#x0D; Key word : Chronic Renal Failure,Thyroid Hormones.

The effect of chronic renal failure on cardiac function: an experimental study with a rat model.

Chronic renal failure (CRF) is a risk factor for cardiovascular disease, and recently much interest has focused on the cardiorenal syndrome. However, the relationship between CRF and cardiac function is not fully understood. We investigated the effect of CRF on cardiac function in a rat model. Male Wistar rats (7weeks old) were randomly divided into the following two groups: (1) control group (n=5) and (2) CRF group (n=18). Rats in the CRF group received an adenine suspension orally for 10days. Measurements of blood pressure and echocardiography were performed at baseline and after 17weeks (24weeks old). To investigate the possible effect of hypertension on cardiac function, we analyzed rats in the CRF group with and without hypertension (systolic blood pressure ≥ or <130mmHg at 17weeks) separately. Creatinine was significantly higher in the CRF group than in the control group. At 17weeks, rats in the CRF group showed preserved systolic function but diastolic dysfunction with decreased mitral early diastolic filling velocity and annular velocity. In both the normotensive and hypertensive CRF rats, early diastolic mitral annular velocity was significantly lower than in the control group. Myocardial fibrosis was not found in all groups, but myocardial apoptosis was found in the CRF group irrespective of the presence or absence of hypertension. The adenine-induced CRF rat model developed renal dysfunction and left ventricular diastolic dysfunction independent of the presence of hypertension.

Effects of Chronic Renal Failure on Brain Cytochrome P450 in Rats.

Chronic renal failure (CRF) impedes renal excretion of drugs and their metabolism by reducing the expression of liver cytochrome P450 (P450). Uremic serum contains factors, such as parathyroid hormone (PTH), that decrease liver P450s. The P450s are also involved in the metabolism of xenobiotics in the brain. This study investigates: 1) the effects of CRF on rat brain P450, 2) the role of PTH in the downregulation of brain P450s in CRF rats, and 3) the effects of PTH on P450s in astrocytes. Protein and mRNA expression of P450s were assessed in the brain of CRF and control (CTL) rats, as well as from CTL or CRF rats that underwent parathyroidectomy (PTX) 1 week before nephrectomy. CYP3A activity was measured using 3-[(3, 4-difluorobenzyl) oxy]-5, 5-dimethyl-4-[4-methylsulfonyl) phenyl] furan-2(5H)-1 metabolism in brain microsomal preparation. CYP3A protein expression was assessed in primary cultured astrocytes incubated with serum obtained from CRF or CTL rats or with PTH. Significant downregulations (≥40%) of CYP1A, CYP2C11, and CYP3A proteins were observed in microsomes from CRF rat brains. CYP3A activity reduction was also observed. CYP3A expression and activity were unaffected in PTX-pretreated CRF rats. Serum of PTX-treated CRF rats had no impact on CYP3A levels in astrocytes compared with that of untreated CRF rats. Finally, PTH addition to normal calf serum induced a reduction in CYP3A protein similar to CRF serum, suggesting that CRF-induced hyperparathyroidism is associated with a significant decrease in P450 drug-metabolizing enzymes in the brain, which may have implications in drug response.

Ultrasonographic evaluation of the femoral cartilage thickness in patients with chronic renal failure

Objective To investigate the effects of chronic renal failure (CRF) on the distal femoral cartilage thickness by using ultrasonography and to determine the relationship between cartilage thickness and certain disease-related parameters. Design Fifty-seven CRF patients (41 male and 16 female) (mean [SD] age, 44.7 [12.1] years) and 60 healthy controls (41 male and 19 female) (mean [SD] age, 43.5 [13.3] years) were enrolled in this study. Demographic and clinical characteristics were recorded. Cartilage thickness measurements were taken from the medial and lateral condyles, and intercondylar areas of both knees. Results Groups were similar in terms of age, weight, height, body mass index and gender (all p>0.05). The mean cartilage thickness was found to be less in CRF patients than in controls (statistically significant for medial condyles and intercondylar areas both in right and the left knees [all p<0.05]). Cartilage thickness showed no correlation with eGFR, and with the levels of serum urea, creatinine, calcium, magnesium, phosphor, hemoglobin, uric acid and as well as steroid use (all p>0.05) in CRF patients. Conclusion In the light of our findings, we imply that patients with CRF have thinner femoral cartilage than healthy controls. This result may support the view that patients with CRF are at increased risk for developing early knee osteoarthritis. Last but not least, clinicians should be aware of the importance of rehabilitation strategies aimed at decreasing onset and progression of knee osteoarthritis in patients with CRF.

Effect of chronic renal failure on voice: an acoustic and aerodynamic analysis

Abstract This study was conducted to investigate the effect of chronic renal failure (CRF) on acoustic and aerodynamic parameters of voice and to compare the results with a group of individuals with normal renal function. The participants in this study were divided into two groups. A clinical group (the patient group) consisted of 66 adults diagnosed as having CRF (26 male patients and 40 female patients), with their age ranging from 19 to 68 years. The control group consisted of 66 healthy adults (36 male individuals and 30 female individuals). Their age ranged from 20 to 60 years and they did not have any impairment in renal function or any complaints concerning their voice. All participants underwent evaluation of their voice acoustically and aerodynamically. Acoustic analysis was performed using computerized speech lab. The acoustic parameters studied include average pitch, jitter, shimmer, and noise-to-harmonic ratio. Aerodynamic analysis was performed using Aerophone II Model 6800. The aerodynamic parameters studied include vital capacity, maximum phonation time, phonation quotient, mean flow rate, subglottic pressure, and glottal efficiency. The data were analyzed using the independent t-test to compare the significance of difference between means across the two groups. In acoustic analysis, there was a significant increase in pitch in male patients with CRF and an increase in shimmer with borderline significance in the total group with CRF. The total group as well as the female subgroup with CRF showed a significant increase in noise-to-harmonic ratio. With respect to the aerodynamic analysis, the total group as well as the male and female subgroups with CRF showed a significant decrease in the vital capacity. There was also a significant decrease in the maximum phonation time in the total and female subgroup with CRF. Participants with CRF exhibit clinical evidence of voice disorders both acoustically and aerodynamically. Hence, the present study sheds light on the interplay of different body systems and laryngeal muscles.

Effect of end-stage renal disease on oral health in patients undergoing renal dialysis: A cross-sectional study

Aims and Objectives:To evaluate the effect of chronic renal failure on oral health in renal dialysis patients. To assess and improvise awareness of staff regarding oral health care of the patients in hemodialysis unit.Materials and Methods:A cross-sectional questionnaire survey and oral health examination study were conducted on 206 end-stage chronic renal failure patients (stage V) who were undergoing renal dialysis in Guntur city. The study included the questionnaire form and modified WHO proforma to record their oral health status. Oral examination was done in American Dental Association (ADA) type III method by using mouth mirror and community periodontal index (CPI) probe. Questionnaire survey was conducted among the nursing staff in the hemodialysis unit.Results:Mean age of the study subjects was 46.79 ± 12.78 years; 81.1% were males and 18.9% were females. Candidiasis (8.3%) was the most frequently seen oral mucosal condition in these subjects. Majority of the subjects (44.2%) showed periodontal diseases (CPI score 3: Pocket depth of 4-5 mm). Caries prevalence of 56.3% was seen in this study group. Higher incidence of hepatitis C was significantly associated with higher duration of dialysis. There was very little awareness among the nursing staff regarding dental care.Conclusion:There is greater deterioration of periodontal health among dialysis patients with chronic renal disease. Awareness regarding dental care is very less among patients undergoing renal dialysis. These patients should be monitored carefully to maintain their oral health. Awareness must be increased among dialysis patients and nursing staff about the need for primary prevention of dental diseases.

Effect of chronic renal failure on the hepatic, intestinal, and renal expression of bile acid transporters

Although the kidney is believed to play a minor role in bile acid (BA) excretion, chronic renal failure (CRF) has been reported to be associated with increased serum bile acid levels and alterations in BA homeostasis. The mechanisms for elevated BA levels are poorly understood in both clinical and experimental studies. This study was designed to examine the effects of naturally progressing CRF of longer duration on the hepatic and renal mRNA and protein levels of the BA-synthesizing enzyme Cyp7a1 and the BA transporters Ntcp, Bsep, Mrp3, Ost-α, and Ost-β. Sprague-Dawley rats were randomized to the CRF group (&frac56; nephrectomy) or to the sham-operated control group and were analyzed 8 wk after surgery. Results obtained in the CRF rats were compared with those obtained in rats that had undergone uninephrectomy (UNX). The CRF group exhibited significantly increased plasma cholesterol and BA concentrations. Hepatic Cyp7a1 mRNA and protein levels were almost identical in the two groups. Hepatic Mrp3, Ost-α, and Ost-β expression was increased, suggesting increased basolateral efflux of bile acids into the blood. However, no such changes in BA transporter expression were observed in the remnant kidney. In UNX rats, similar changes in plasma BA levels and in the expression of BA transporters were found. We hypothesize that the increase in plasma BA is an early event in the progression of CRF and is caused by increased efflux across the basolateral hepatocyte membrane.

Changes in B-Group Vitamin Status in Adenine-Induced Chronic Renal Failure Rats

The purpose of this study was to determine the effects of chronic renal failure (CRF) on B-group vitamin status using model rats in which adenine-induced CRF. We measured B-groups vitamins in the urine, blood, liver, and kidney. These results showed that renal failure affected the distribution, metabolism, and renal clearance of water-soluble vitamins, and that the effects were different with each vitamin.

Effects of Chronic Renal Failure on Brain Drug Transporters in Rats

Studies demonstrated that chronic renal failure (CRF) affects the expression and activity of intestinal, hepatic, and renal drug transporters. Such drug transporters are expressed in brain cells and at the blood-brain barrier (BBB), where they limit the entry and distribution of drugs in the brain. Perturbations in brain drug transporter equilibrium by CRF could lead to central drug toxicity. This study evaluates how CRF affects BBB drug transporters using a 5/6 nephrectomized rat model. Protein and mRNA expression of influx transporters [organic anion-transporting polypeptide (Oatp), organic anion transporter (Oat)] and efflux transporters [P-glycoprotein (P-gp), multidrug resistance-related protein (Mrp), breast cancer resistance protein (Bcrp)] were measured in CRF and control rat brain. Intracerebral accumulation of radiolabeled benzylpenicillin, digoxin, doxorubicin, and verapamil was used to evaluate BBB drug permeability. Protein expression of the transporters was evaluated in rat brain endothelial cells (RBECs) and astrocytes incubated with control and CRF rat serum. We demonstrated significant decreases (30-50%) in protein and mRNA levels of Bcrp, Mrp2 to -4, Oat3, Oatp2 and -3, and P-gp in CRF rat brain biopsies, as well as in astrocytes and RBECs incubated with CRF serum. These decreases did not correlate with in vivo changes because BBB permeability of benzylpenicillin was decreased by 30% in CRF rats, whereas digoxin, doxorubicin, and verapamil permeabilities were unchanged. It thus seems that even with decreased drug transporters, BBB integrity and function is conserved in CRF.

Effects of Chronic Renal Failure on Gastrointestinal Motility: A Study on the Changes of Gastric Emptying, Small Intestinal Transit, Interdigestive Myoelectric Complex, and Fecal Water Content

Background: Gastrointestinal (GI) dysfunction may lead to malnutrition in patients with chronic renal failure (CRF). This study investigated the effects of CRF on GI motility. Methods: Forty-eight Sprague Dawley rats (180 ± 20 g) were randomly classified into CRF group and sham-operated (Sham) group, and each group was further assigned for gastric emptying (GE), small intestinal transit (SIT), interdigestive myoelectric complex (IMC), and fecal water content (FWC) experiments (6 CRF and 6 Sham rats per experiment). The CRF model was established by 5/6 nephrectomy. The body weight (BT), GE, SIT, IMC, and FWC of the rats were observed. ANOVA and Student–Newman–Keuls q-test were utilized to do statistical analysis. Results: The BT of the rats in the two groups had no statistical difference before surgery. But in the ninth week after surgery, the CRF rats (230 ± 20 g) weighed less than the Sham rats (260 ± 15 g) (p < 0.05). The GE rate and SIT rate in CRF rats were significantly lower than that of Sham rats (GE 33.08 ± 7.50 vs. 53.37 ± 9.78%; SIT 42.92 ± 8.96 vs. 58.67 ± 9.12%) (p < 0.05). Compared with the IMC of the Sham rats, the CRF rats showed obvious alterations in (a) IMC cycle; (b) phase II and phase III duration; and (c) phase III cycling frequency, amplitude, and percentage (p < 0.05). FWC of the CRF rats increased significantly (p < 0.05). Conclusion: The GI motility of the CRF rats is obviously impaired. This finding may indicate that the effects of CRF on GI motility might be relatively prevalent.

Effects of Chronic Renal Failure on Kidney Drug Transporters and Cytochrome P450 in Rats

Chronic renal failure (CRF) leads to decreased drug renal clearance due to a reduction in the glomerular filtration rate. However, little is known about how renal failure affects renal metabolism and elimination of drugs. Because both depend on the activity of uptake and efflux by renal transporters as well as enzymes in tubular cells, the purpose of this study was to investigate the effects of CRF on the expression and activity of select renal drug transporters and cytochrome P450. Two groups of rats were studied: control and CRF (induced by 5/6 nephrectomy). Compared with control rats, we observed reductions in the expression of both protein and mRNA of Cyp1a, sodium-dependent phosphate transport protein 1, organic anion transporter (Oat)1, 2, and 3, OatK1/K2, organic anion-transporting polypeptide (Oatp)1 and 4c1, P-glycoprotein, and urate transporter 1, whereas an induction in the protein and mRNA expression of Mrp2, 3, and 4 and Oatp2 and 3 was observed. Cyp3a expression remained unchanged. Similar results were obtained by incubating a human proximal tubule cell line (human kidney-2) with sera from CRF rats, suggesting the presence of uremic modulators. Finally, the renal elimination of [(3)H]digoxin and [(14)C]benzylpenicillin was decreased in CRF rats, compared with controls, as shown by a 4- and 9-fold accumulation, respectively, of these drugs in kidneys of rats in CRF. Our results demonstrate that CRF affects the expression and activity of several kidney drug transporters leading to the intrarenal accumulation of drugs and reduced renal clearance that could, at least partially, explain the tubular toxicity of many drugs.