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Proton/peptide cotransporter (PEPT 2) from human kidney: functional characterization and chromosomal localization.

We report here on the functional characterization of the H+/peptide cotransporter PEPT 2 cloned from human kidney and on the chromosomal localization of the PEPT 2 gene. PEPT 2, when functionally expressed in HeLa cells, induces the transport of the neutral dipeptide glycylsarcosine. The induced transport activity is markedly influenced by extracellular pH. The optimum pH for the transport process is 6.0-7.0. Kinetic analysis has revealed that PEPT 2 is a high-affinity transporter, the Michaelis-Menten constant for glycylsarcosine being 74 +/- 14 microM. The human intestinal H+/peptide cotransporter PEPT 1 has 4-fold less affinity for the dipeptide under identical experimental conditions. Studies with other chemically diverse dipeptides have established that PEPT 2 possesses higher affinity than PEPT 1 not only for neutral peptides but also for peptides consisting of anionic and/or cationic amino acids. Somatic cell hybrid analysis and in situ hybridization have shown that the gene encoding PEPT 2 maps to human chromosome 3q13.3-q21.

Carrier Proteins↗

Kidney transplant artery stenosis. Interrelationship between blood pressure, kidney function, renin-aldosterone system and body sodium content.

Among 9 hypertensive recipients with kidney transplant artery stenosis (KTAS) evidence of increased activity of the renin system was present in 3. Surgical repair of KTAS in 4 recipients resulted in an increase in renal plasma flow and glomerular filtration rate associated with a decrease in exchangeable sodium and blood pressure. Peripheral plasma renin and aldosterone values were normal before and after operation in all. It is suggested that sodium retention may counterbalance increased activity of the renin system in KTAS. Preoperative determinations of plasma renin do not predict the effect of surgical repair of KTAS on hypertension.

Adult↗

[Prenatal diagnosis of disorders of fetal kidney function--a critical analysis of 95 cases].

Ninety-five gravidae were examined at Düsseldorf University Gynecological Clinic for assessment of the fetal renal system. Suspected disorders were ruled out in 33 cases by sonography. Urogenital malformations without major loss of function were diagnosed in 25 fetuses. The prognosis was unfavorable in 15, and 22 fetuses had other disorders. In 5 out of 22 infants on whom autopsy was performed, the kidneys were found to be normally developed, contrary to the sonographic diagnosis. However, all five of these infants had anomalies of the umbilical artery. It is well known that cases of anhydramnios in the first half of pregnancy have a poor prognosis. In order to assess such cases better, the authors consider the following examination procedure appropriate: 1) filling with amniotic fluid; 2) Lasix provocation test; 3) thorough sonographic examination of the fetus; 4) karyotyping; and 5) identification of maternal infections. It is at present impossible to say whether there is a statistical relationship between changes in the umbilical cord and disorders of renal function.

Amniotic Fluid↗

Kidney function of single comb white Leghorn pullets following acute renal portal infusion of the mycotoxin citrinin.

Poultry consuming diets contaminated with citrinin excrete copious quantities of urine and exhibit increased water consumption. The present study was conducted to determine if citrinin acts directly on the kidneys and, if so, to provide a detailed physiological evaluation of the nephrotoxic effects of citrinin. Single Comb White Leghorn pullets were anesthetized and prepared for renal function studies. Ureteral urine was collected during a pre-infusion period (30 min), during unilateral renal portal infusion of 200 ppm citrinin (30 min), and during a recovery period following citrinin infusion (90 min). Pilot studies had shown that 200 ppm citrinin is the lowest dose capable of causing consistent unilateral responses when infused at a rate of .2 ml/kg body weight (BW) X min. The responses of the portal-infused kidneys were compared with the responses of the contralateral (uninfused) kidneys to determine the direct effects of citrinin. Citrinin had no acute direct (unilateral) effect on glomerular filtration rate, renal plasma flow rate, urine pH, or fractional calcium or magnesium excretion. Citrinin caused rapid unilateral increases in urine flow rates, free water clearance, and in fractional sodium, potassium, and inorganic phosphate excretion. Increased solute excretion did not compensate for increased free water clearance, as reflected by a significant decrease in urine osmolality. Recovery from the effects of citrinin occurred within 30 min after cessation of unilateral renal portal infusion. No histopathological damage was seen when citrinin was infused at 200 and 800 ppm, although dose-related increases in urine flow and decreases in urine osmolality were observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Glutamate transport asymmetry and metabolism in the functioning kidney.

Renal glutamate extraction in vivo shows a preference for the uptake of D-glutamate on the antiluminal and L-glutamate on the luminal tubule surface. To characterize this functional asymmetry, we isolated rat kidneys and perfused them with an artificial plasma solution containing either D- or L-glutamate alone or in combination with the system X-AG specific transport inhibitor, D-aspartate. To confirm that removal of glutamate represented transport into tubule cells, we monitored products formed as the result of intracellular metabolism and related these to the uptake process. Perfusion with D-glutamate alone resulted in a removal rate that equaled or exceeded the L-glutamate removal rate, with uptake predominantly across the antiluminal surface; L-glutamate uptake occurred nearly equally across both luminal and antiluminal surfaces. Thus the preferential uptake of D-glutamate at the antiluminal and L-glutamate at the luminal surface confirms the transport asymmetry observed in vivo. Equimolar D-aspartate concentration blocked most of the antiluminal D-glutamate uptake and a significant portion of the luminal L-glutamate uptake, consistent with system X-AG activity at both sites. D-Glutamate uptake was associated with 5-oxo-D-proline production, whereas L-glutamate uptake supported both glutamine and 5-oxo-L-proline formation; D-aspartate reduced production of both 5-oxoproline and glutamine. The presence of system X-AG activity on both the luminal and antiluminal tubule surfaces, exhibiting different reactivity toward L- and D-glutamate suggests that functional asymmetry may reflect two different X-AG transporter subtypes.

Animals↗

L-arginine ameliorates kidney function and urinary bladder sensitivity in experimentally-induced renal dysfunction in rats.

Effects of L-arginine and NG-nitro-L-arginine methyl ester (L-NAME) on the renal dysfunction that is induced by cisplatin (CDDP) were investigated. A single dose of CDDP (7.5 mg/kg i.p.) induced renotoxicity, which was manifested by increasing the sensitivity of isolated urinary bladder rings to acetylcholine (ACh), together with a significant elevation of serum urea and creatinine, and a severe decrease in serum albumin. Moreover, renal dysfunction was further confirmed by a significant decrease of enzyme activities, such as glutathione peroxidase, GSH-Px (E.C 1.11.1.9), catalase (E.C 1.11.1.6), as well as a significant increase in lipid peroxides that were measured as malondialdhyde (MDA) in kidney tissue homogenates. The administration of L-arginine (70 mg/kg/d p.o in drinking water 5 d before and 5 d after the CDDP injection) significantly ameliorated the renotoxic effects of CDDP, as judged by restoring the normal responses of isolated bladder rings to Ach, and also by an improvement in a range of renal function indices, which included serum urea and creatinine concentrations and kidney weight. In addition, L-arginine prevents the rise of MDA, as well as a reduction of GSH-Px and catalase activities in kidney tissues homogenates. On the other hand, the administration of L-NAME (4 mg/kg/d p.o) resulted in no protection against renal dysfunction that was induced by CDDP treatment. The findings of this study suggest that L-arginine can attenuate kidney injury that is produced by CDDP treatment. In addition, L-arginine may be a beneficial remedy for CDDP-induced renal toxicity, and could be used to improve the therapeutic index of CDDP.

Acetylcholine↗

[Renal transplantation: surgery in the patient with a functioning kidney].

One hundred and seven surgical procedures performed on 98 patients with stable renal allograft function are analyzed. They represent 35.5% of 276 patients who underwent renal transplants. The surgical procedures were not related to the graft or its arteries and vein. The procedures were gynecologic 8, urologic 24, thoracic 6, ophthalmologic 8, neurosurgical 2, general surgery 37, orthopedic 17 and plastic surgery 5. Thirty-five (32.7%) were emergency and 72 (67.3%) elective procedures. Twenty-six patients were operated on for infections. The overall operative mortality rate was 15.3%. It was significantly higher in emergency procedures (34.28%) than in elective surgery (4.16%).

Adolescent↗

Effect of HLA matching on cadaver kidney function: experience at a single large center.

Whenever the results are compared within a given time period, within a given age group, within the nondiabetic population, and within groups receiving high or low doses of ALG, the advantages of well-matched kidneys continually and significantly demonstrate themselves. Tissue matching failed to improve survival and function only in diabetic patients who frequently die of problems unrelated to rejection. The results thus demonstrate an overall clear superiority in patient survival and transplant function of the better-matched kidneys.

Cadaver↗

Adenosine mediates tubuloglomerular feedback response: an element of metabolic control of kidney function.

Numerous studies have shown during the past 10 years that adenosine is present in the normoxic kidney and accumulates when ATP hydrolysis prevails over ATP synthesis. Local generation of adenosine by the macula densa cells and its release into the interstitium of the juxtaglomerular apparatus (JGA) is considered to be the link between the enhanced NaCl concentration in the tubular fluid and the subsequent responses including preglomerular vasoconstriction and reduction of renin release by the juxtaglomerular cells. Micropuncture and microperfusion experiments using specific adenosine agonists and antagonists support the concept that adenosine functions as a mediator in the signal transmission of the JGA.

Adenosine↗

Evaluation of kidney function in dogs suffering from canine encephalitozoonosis by standard clinical pathological and radiopharmaceutical techniques.

Canine encephalitozoonosis can be responsible for a severe renal disease in dogs which may develop into progressive, irreversible kidney failure. Three pure-bred Boxer littermates with confirmed encephalitozoonosis were subjected to sequential clinical pathological tests and renal biopsies. The endogenous serum creatinine and urea levels showed an initial temporary reduction but later increased steadily. The phenolsulphonphthalein retention test confirmed this end-stage renal disease. Initial hyper-gamma globulinaemia showed a rapid decline. Urinalysis was an indicator of chronic renal disease and the kidney biopsies confirmed progressive irreversible kidney lesions. Evaluation of sequential tests are advocated for the setting of a prognosis. The radiopharmaceutical techniques employed proved to be sensitive indicators of renal dysfunction and a means of evaluating the function of the left and right kidney separately.

Animals↗

[Follow-up of kidney function in children with former posterior urethral valves].

Severe forms of posterior urethral valves involve the risk of upper urinary tract damage and impaired renal function. For this reason, 26 boys formerly (between January 1980 and December 1989) treated for high-grade urethral obstruction were re-examined with reference to renal function. Results were compared with observations in a control group of 26 boys matched for age and height undergoing minimal urological surgery. While there were no significant differences in haemoglobin, height, blood pressure or kidney volume, in 14 of 20 patients with normal glomerular filtration rate pathologic findings were recorded, most of which related to urine concentrating capacity, tubular phosphate handling and hyperparathyroidism. These observations necessarily have implications for treatment of such children even if they are assumed to have unimpaired renal function. In future, monitoring of renal function in children with former posterior urethral valves should include different tests, and in particular tests of concentration capacity and measurement of parathyroid hormone.

Child↗

Restoration of kidney function after prolonged renal artery occlusion.

An 11-month-old child developed renal artery occlusion (RAO) and anuric renal failure following an unsuccessful transluminal renal artery angioplasty of a solitary kidney. Despite the prolonged period of anuria, kidney viability was suspected based upon preservation of kidney length and the absence of glomerulosclerosis. At 19 months of age, revascularization of the kidney was performed. During the 7 months following revascularization, renal function gradually improved so that dialysis was no longer necessary. This improvement occurred in spite of significant tubular atrophy. Kidney viability may have been preserved, despite prolonged ischemia, as a result of the decreased renal oxygen consumption that existed during subfiltration glomerular perfusion pressures. The low normal blood erythropoietin level may have reflected the lack of renal hypoxia. The ability of the kidney to adapt to chronic ischemia underscores the importance of considering vascular reconstruction in all patients with RAO despite a long period of non-function.

Humans↗

Can a transplanted living donor kidney function equivalently to its native partner?

Early renal functional adaptation was examined in 81 haploidentical donor and recipient pairs, as well as long-term stability of glomerular filtration rate (GFR) in 78 recipients. GFR was determined pre- and 1 month postnephrectomy in donors and 1 month post-transplant and yearly thereafter in recipients. Compensatory increase in filtration (CIF) of transplanted and native kidneys was calculated using donor pretransplant GFR: [CIF= (GFR at 1 month/donor prenephrectomy GFR) x 100]. Annual rates of change in GFR were estimated using within-patient linear regression analysis (slopes). Recipients without rejection (n = 62) and their donors had similar early GFR and CIF. Those with acute rejection (n = 19) had significantly lower GFR and CIF than their donors (61 +/- 16 mL/min/1.73 m2 and 57 +/- 14% vs. 75 +/- 11 and 69 +/- 9; p = 0.01 and p < 0.001). Recipients without cyclosporine (n = 52) had 1 month GFR and CIF of 70 +/- 14 and 67 +/- 14 vs. 72 +/- 11 and 69 +/- 11 for their donors. Those with cyclosporine (n = 29) had 1 month GFR and CIF of 64 +/- 14 and 62 +/- 16 vs. 69 +/- 12 and 67 +/- 11 for their donors (p = 0.15 and 0.16). Comparison of median (25th, 75th) rates of change of GFR with and without acute rejection or cyclosporine did not demonstrate significant effects of either on stability of allograft function, although there was a trend towards greater loss of GFR in cyclosporine-treated patients [-1.1 (-2.5, 0.8) vs. 0.0 (-1.8, 1.2) mL/min/1.73 m2/year, p = 0.47]. We conclude that, in the absence of rejection, the transplanted kidney maintains the same capacity for functional adaptation as its native partner. Therapy with cyclosporine does not significantly inhibit early physiological adaptation of renal transplants.

Cyclosporine↗