Pharmacokinetics of bezafibrate after single and multiple doses in the presence of renal failure

Summary The pharmacokinetics of bezafibrate were investigated in the serum and urine of 22 patients with impaired renal function of different degrees after a single oral dose. The results of the first study were checked by a second study in another 12 patients with advanced renal insufficiency using multiple dosing. Both studies revealed an almost identical hyperbolic relationship between the mean serum concentration over 24 h and the endogenous creatinine clearance. Since the vertex of this hyperbola is positioned at a creatinine clearance of 50 ml/min, only greater impairment of the renal function requires dose reduction, the respective nomograms and schedules for which are given. Even in advanced renal failure (creatinine clearance 10–25 ml/min) the total serum clearance of bezafibrate was considerably higher (27 ml/min) than that reported in the literature for clofibric acid. It is of interest to note that not only the renal but also the extrarenal clearance, which in normals accounts for approximately half of the total clearance of bezafibrate, was considerably depressed in advanced renal failure. This might indicate that part of the extrarenal mechanism of bezafibrate elimination, e.g. the glucuronidation, might occur in the kidneys. Knowledge of the kinetic behaviour of bezafibrate in patients with impaired renal function also allows rational therapy in the presence of this condition.     

The influence of ischemia on 131I-Hippuran renograms performed after kidney transplantation and its prognostic value

Within 72 hours after 289 uncomplicated cadaver kidney transplantations, 131I-ortho-iodo-hippurate renography was performed. The renographic changes caused by ischemic damage were correlated to the length of warm and cold ischemia times and followed during the recovery of graft function. Normal or slightly decreased phase 1 and 2 were seen in approximately 65 percent of the renograms if warm ischemia time was shorter than 15 min and the cold ischemic period less than 10 hours. For cold ischemia longer than 10 hours, the proportion was 30-60 percent. Warm ischemia time between 15 and 30 min caused a decrease of phase 1 and 2. Approximately 40 percent were normal or reduced if the cold ischemia time was less than 10 hours; for longer than 10 hours, the proportion was approximately 30 percent. Renograms with an excretion phase were mainly seen in the group with warm ischemia time less than 15 min combined with cold preservation for less than 20 hours. The phases of the post transplant renograms were closely correlated to the creatinine clearance. A normal or slightly decreased phase 1 or 2 was seen in patients with a clearance of 20-35 ml/min, moderately decreased phase was seen in the group with clearance of 10 ml/min, severely changed phase in the group with clearance of 0-5 ml/min. Correlating the onset of renal function to the initial posttransplant renogram showed immediate onset of function of 65 percent of the grafts with a normal or slightly decreased phase 1 or 2, as opposed to 15 percent of the grafts with moderately to severely decreased phases.(ABSTRACT TRUNCATED AT 250 WORDS)     

Clearance and renal extraction of technetium-99m-L,L-ethylenedicysteine, I-131-ortho-iodohippurate and I-125-iothalamate in pigs.

99mTc-L,L-ethylenedicysteine (99mTc-EC) has been proposed as a 99mTc-labelled alternative to radio-iodinated ortho-iodohippurate (OIH) for renal imaging and evaluation of renal function. The kinetics of this new renal function agent were studied by a single-injection plasma clearance technique in pigs. 99mTc-EC, 131I-OIH and 125I-iothalamate were injected and the plasma concentration of the three tracers was followed for 240 min. Renal, hepatic and total plasma clearance were calculated. There was no difference between the renal plasma clearance of 99mTc-EC and 131I-OIH (175 +/- 9 versus 178 +/- 8 ml min-1, P = 0.43), whereas the difference between the total plasma clearance of 99mTc-EC and 131I-OIH was highly significant (268 +/- 16 versus 185 +/- 9 ml min-1, P = 0.0001). 99mTc-EC had a significant hepatic clearance of 83 +/- 10 ml min-1 whereas the hepatic clearance of 131I-OIH was negligible. Renal plasma extraction of both 99mTc-EC and 131I-OIH decreased significantly between 2 and 240 min post-injection from 0.85 to 0.45% for 99mTc-EC and from 0.93 to 0.57% for 131I-OIH. Red blood cell binding of 99mTc-EC and 131I-OIH was 6.1% and 20%, respectively. The protein binding of 99mTc-EC and 131I-OIH was 32% for both tracers. We conclude that 99mTc-EC is not a suitable tracer for measuring renal function by the single-injection plasma clearance technique in pigs. This is due to a decreasing renal extraction and a significant hepatic clearance.     

Cytotoxic activity of graft-infiltrating lymphocytes correlates with cellular rejection in cardiac transplant patients

Lymphocytes propagated from allografts have shown a wide spectrum of activity during rejection including cytotoxicity, proliferation, and lymphokine production. It is necessary to correlate these activities to the rejection process to understand the in vivo immune response. The frequent need to obtain a biopsy of human cardiac allografts permits the evaluation of the function of the graft-infiltrating lymphocytes (GIL) as related to development of the rejection process. Lymphocyte cultures established from biopsies taken before, during, and after rejection episodes of grade 1.0 or greater were assayed for surface antigen expression using flow cytometry, proliferative activity using a primed lymphocyte test (PLT), and cytotoxicity using a cell-mediated lympholysis assay. Fifteen rejection episodes were followed from 10 patients. Two patients were followed through two different rejection episodes and one patient through four rejection episodes. CD8+ cells usually predominated during the rejection episode. Following the rejection episodes the GIL showed a shift toward higher proportion of CD4+ cells. Most cultures taken prior to and during rejection episodes (8/9 and 12/13 assayed, respectively) demonstrated> 30% killing of targets bearing donor-related HLA antigens. Seven of 15 cultures remained cytotoxic after a rejection episode whereas 8 of 15 lost cytotoxicity. The patients whose cultures remained cytotoxic after a rejection episode went on to further rejection episodes at 6, 7, 11, 20, 37, or 118 days later. Those patients whose cultures were no longer cytotoxic did not experience any subsequent rejection episode until at least 257 days later. Persistence of alloreactivity, as indicated by the ability to proliferate in a PLT, did not predict future rejection episodes. These results suggest that the cytotoxic activity of the interleukin-2 responsive T lymphocytes in the biopsies is closely related to clinical rejection, and continued cytotoxicity may be a useful prognostic indicator of future rejection episodes. Human Immunology 32, 241–245 (1991)     

^99mTc-DTPA肾动态显像及β2-m水平在评价肾移植受者肾功能中的价值

目的：探讨^99mTc-DTPA肾动态显像半定量参数和血、尿β2-m水平测定对肾移植术后早期并发症诊断与鉴别诊断的价值。方法：28例肾移植病人术后均进行放射性核素^99mTc-DTPA肾动态显像,同时测定移植肾的肾小球滤过率（GFR）、膀胱放射性计数与移植肾放射性计数比值（B/K值）和移植肾放射性1min计数与腹主动脉放射性1min计数比值（K1min/A1min比值）。在进行放射性核素肾动态显像前所有病人均收集其血液和尿液标本,采用放射免疫分析测定血、尿β2-m水平。结果：12例肾功能正常者肾动态显像示肾血流灌注及功能良好,GFR值为（49.1±6.1）ml/min,B/K值均〉3,K1min/A1min比值为8.18±1.41;4例急性排斥反应者肾血流灌注受损程度重于功能相,GFR值为（33.2±5.3）ml/min,B/K值均〈1,K1min/A1min比值为2.59±0.86,β2-m水平以血β2-m升高明显;8例慢性排斥反应者肾血流灌注和功能相均同时受损,GFR值为（19.8±7.5）ml/min,B/K值均〈1,K1min/A1min比值为2.19±0.84,β2-m水平也以血中升高明显;2例肾小管坏死者及2例环孢素A肾中毒者肾血流灌注受损均轻于功能相,GFR值分别为（38.5±4.1）ml/min和（39.4±5.81）ml/min,B/K值均〈1,K1min/A1min比值分别为5.83±0.84和6.01±0.66,β2-m水平以尿中升高显著。结论：放射性核素肾动态显像半定量参数K1min/A1min比值和B/K值,结合肾移植病人术后血、尿β2-m水平联合分析可早期初步鉴别排斥反应的类别,可作为判断移植肾受损程度、原因及预后估测的敏感指标。     

Serumspiegel und Urinausscheidung von L-Carnitin bei Patienten mit normaler und eingeschränkter Nierenfunktion

Summary The influence of age, sex, and renal function on serum levels and urinary excretion of free carnitine was studied in 187 subjects. Sixty-one subjects with normal renal function (creatinine clearance >100 ml/min) showed a serum carnitine level of 72.2±23.2 µmol/l. The carnitine values of males (76.8±23.3 µmol/l,n=39) were higher (p<0.05) than those of females (64.0±21.0 µmol/l, n=22). Carnitine levels did not correlate with age. Values in patients with normal renal function did not differ from serum carnitine levels in healthy controls (74.7±17.5 µmol/l,n=49). The mean urinary carnitine excretion per day was 163.5 µmol (range 63.7–419.6 µmol) in patients with intact renal function. Extreme impairment of glomerular filtration rate (creatinine clearance <20 ml/min) resulted in higher carnitine concentrations in serum (108.9±39.4 µmol/l,n=18,p<0.05), lower carnitine elimination per day (78.5 µmol, range 14.5–424.3 µmol,n=18,p<0.05) and a decreased carnitine clearance (0.8 ml/min, range 0.2–3.8 ml/min).These data together with earlier results obtained in dialysis patients suggest that carnitine metabolism in renal failure is altered by reduction of both endogenous carnitine biosynthesis and renal carnitine clearance.

     

Effect of quinine on plasma digoxin concentration and renal digoxin clearance

In order to explore the digoxin-quinine interaction, digoxin steady state pharmacokinetics was studied before and during quinine coadministration in seven healthy subjects. Quinine (250 mg/day) increased mean plasma digoxin concentration from 0.64 +/- 0.12 to 0.80 +/- 0.18 ng/ml (p less than 0.05) within one week. Urinary digoxin recovery rose from 154.0 +/- 18.8 to 181.5 +/- 22.6 micrograms/24 h (p less than 0.01), whereas renal digoxin clearance was unaltered in the presence of quinine (181.5 +/- 24.2 vs. 174.1 +/- 26.5 ml/min). An increase in quinine dose (to 750 mg/day) caused further increments in plasma digoxin levels, whereas renal digoxin clearance remained unchanged. Quinine elevates plasma digoxin concentrations in a stepwise fashion probably due to an impairment of extrarenal digoxin clearance.     

The effect of a meal of meat on glomerular filtration rate in dogs at normal urine flows.

1. The exogenous creatinine clearance of conscious dogs has been measured by a method in which no loading doses of water or saline were given. The urine volume was thus in the normal range, 0-1-0-3ml./min. 2. Under these conditions, the exogenous creatine clearance of fourteen dogs, measured 17 hr after a meal, was 2-74 ml./min kg-1+/-0-54 (s.d.). This is about 40% lower than values usually regarded as "normal." 3. A meal of meat, 10g/kg, increased exogenous creatinine clearance reflects an increase in glomerular filtration rate. Since this occurs with small doses of meat, increase in glomerular filtration may be important in normal renal function of dogs.     

Effect of hemorrhagic shock on renal release of prostaglandin E.

The effect of hemorrhage and reinfusion on renal release of prostaglandin E (PGE), arterial [PGE], mixed-venous [PGE], and renal function was observed in anesthetized dogs. Following hemorrhage to 60 mmHg arterial pressure, arterial [PGE] rose significantly from 405 to 740 pg/ml. Renal release of PGE remained near control (8 ng/min), as renal blood flow (RBF) decreased from 4.7 to 2.2 ng/min per gram kidney weight (KW). Mixed-venous [PGE] remained near the control value (960 pg/ml). Reinfusion of shed blood restored RBF to 4.0 ml/min per KW. Renal release of PGE rose significantly to 190 ng/min. Arterial [PGE] remained elevated, but mixed-venous [PGE] was not significantly different from control. Indomethacin, a prostaglandin synthesis inhibitor, caused a significant decrease in renal release of PGE. Arterial [PGE] remained elevated following treatment. The inhibition of PGE release from the kidney by indomethacin indicates that increased renal release of PGE following reinfusion is the result of accelerated PGE synthesis. The data suggest that the elevated arterial [PGE] may be the result of alteration of the handling of PGE by the lung.     

移植肾穿刺活组织检查：72例的病理及临床分析

背景：肾移植后慢性排斥反应及各种移植肾病变是移植肾失功能的常见原因,但对移植肾予以准确评估往往非常困难,活检仍是目前的主要手段。 目的：分析肾移植后出现合并症时移植肾穿刺活检的病理结果。 方法：对72例移植肾进行肾穿刺活组织检查,并进行病理诊断及分类,结合移植后情况进行分析。 结果与结论：72例中发生急性细胞介导性排斥反应35例,急性抗体介导性排斥反应12例,移植肾急性药物毒性损伤10例,慢性T细胞介导性排斥反应6例,慢性抗体介导性排斥反应2例,急性肾小管坏死4例,慢性移植肾肾病3例。移植肾组织活检的病理报告与穿刺前临床诊断的符合率在75%以上。移植肾穿刺活检未发生明显的不良反应。提示移植肾活检安全可靠,对肾移植后难以根据临床化验资料作出准确判断肾脏损害的并发症及治疗方案的选择有极为重要的指导意义。     

Renal response to central volume expansion induced by water immersion (WI) in heart transplant patients

This work was aimed to assess the secretion of volume related hormones in heart transplant patients (HTP) and their relationship to excretory renal function studied under bed rest and water immersion conditions. Fractional sodium (FENa%) and potassium (FEK%) clearance, plasma renin activity (PRA), plasma aldosterone (Ald), vasopressin (AVP) and atrial natriuretic peptide (ANP) were estimated in six HTP with moderate renal failure (C creat = 69 +/- 6.9 ml/min) and in 10 healthy subjects (N) (C creat = 110 +/- 2.0 ml/min). All HTP were treated with cyclosporine A and azathioprine. In HTP basal AVP (6.18 +/- 0.92 pg/ml) and ANP (138.17 +/- 14.69 pg/ml) levels were significantly higher than in normals (2.07 +/- 0.11 pg/ml and 74.10 +/- 7.10 pg/ml, respectively). HTP were also characterized by increased FENa% and FEK% both under bed rest (DI) and water immersion (WI) conditions. As abnormalities of excretory renal function in HTP were not significantly related to the plasma endocrine profiles factors other than PRA, Ald, AVP and ANP seemed to be also involved in their pathogenesis.     

Maintenance of residual renal function 10 years after the start of hemodialysis: the advantage of tailored schedules?

Maintenance of residual renal clearance is a clinical advantage, protecting against the long-term effects of uremia: although demonstrated in peritoneal dialysis, the strategies in hemodialysis are less clear. This case suggests that dialysis schedules individualized on the basis of renal clearances may help preserve residual function. SB is a 58 year-old male who started dialysis in emergency (creatinine 30.7 mg/dL) in 1993. He had a history of gout, small shrunken kidneys and moderate hypertension. The clinical diagnosis was vasculointerstitial nephropathy. Eighteen months after starting hemodialysis on a conventional thrice weekly schedule, the patient was switched to 2 sessions/week (creatinine clearance increased to 6 ml/min). Thereafter, clearances were checked in alternate months and treatment was tailored to an equivalent renal clearance > or =12 ml/min (1-2 sessions, 2-3.30 hours/week). Ten years after beginning dialysis, he is on a twice weekly schedule (3.30 hours), is normotensive, works full-time and does not want to go on a transplant waiting list.     

Beta2-microglobulin clearance with super high flux hemodialysis: an ex vivo study

BACKGROUND: Beta2m accumulation induces disease in patients with end-stage renal failure (ESRF). Thus, its removal from patients with ESRF appears desirable. Current dialysis technology, however, has limited effectiveness. AIMS: To measure beta2m clearance with a novel super high flux membrane. DESIGN: Ex vivo experimental study. SETTING: Intensive Care Laboratory of Tertiary institution. SUBJECTS: Six volunteers. MEASUREMENTS AND RESULTS: At a blood flow of 300 ml/min, the clearance of beta2-MG increased from 113.5 +/- 38.5 ml/min with a dialysate flow rate of 200 ml/min to 184.8 +/- 61.1 ml/min with a flow rate of 300 ml/min and 195.0 +/- 60.0 ml/min with a 500 ml/min flow rate. The clearance of albumin was 4.5 ml/min with a dialysate flow rate of 200 ml/min, 5.2 ml/min for a flow rate of 300 ml/min and 5.8 ml/min for a flow rate of 500 ml/min. CONCLUSIONS: High levels of beta2m clearance can be achieved with a super high flux membrane while albumin losses remain limited.     

Studies of cerebral osmoreceptors in anesthetized dogs: the effect of intravenous and intracarotid infusion of hyper-osmolar sodium chloride solutions during sustained water diuresis.

The function of the suggested hypothalamic osmoreceptors was investigated in dogs during light chloralose anesthesia. The dogs were subjected to an i.v. load of 40 ml/kg b.w.t. of a hypo-osmolar solution of sodium chloride and glucose. This degree of hydration was kept constantly by a specially constructed servo system based on the weight of the animal. During water diuresis the renal free water clearance remained essentially constant for several hours (mean about 0.2 ml/kg b.w.t. min). Renal sodium excretion was low (mean 0.82 mumol/kg b.w.t. min) and decreased continuously throughout the experimental period. I.v. infusion of hyperosmolar sodium chloride solution (1.33 mmol/kg b.w.t. in 30 min) was followed by prolonged parallel increases in free water clearance and sodium excretion, without any detectable change in the excretion of osmoles and potassium. The renal response to bilateral infusion of hyper-osmolar NaCl (1.33 mmol/kg b.w.t. in 30 min) into the common carotid arteries was identical to the response to i.v. infusion. The estimated increase in the osmolality of the carotid blood was 2.2%. In seven out of eight experiments intracarotid infusion of NaCl (1.33 mmol/kg b.w.t. in 8 min) did not elicit any reduction in free water clearance. On the contrary, an increase was found similar to that obtained after i.v. infusion. The estimated increase in the osmolality of the carotid blood was 8.4%. The present results question the validity of the currently held view that hypothalamic osmoreceptors play an important role in the control of the osmolality of plasma.     

Phosphodiesterase III inhibitor olprinone chlorate is not significantly removed by continuous venovenous hemodiafiltration

The study objective was to determine whether a phosphodiesterase III inhibitor, olprinone chlorate, is effectively removed by continuous venovenous hemodiafiltration (CVVHDF) in a patient with cardiac and renal failure. The patient was a 73 year old man who had undergone coronary artery bypass grafting for ischemic heart disease and who developed cardiac and renal failure postoperatively. A 0.2 microg/kg per minute dosage of olprinone chlorate was administered intravenously for 120 minutes while the patient was treated with CVVHDF. Samples from the arterial and venous blood catheters and those from the ultradiafiltrate for 12 hours were collected to calculate pharmacokinetic parameters and clearance of hemodiafiltration. The calculated parameters were as follows: half-life of elimination phase: 4.96 hours; total clearance 3.40 ml/min per kg. The clearance of CVVHDF was 0.33 ml/min per kg. The olprinone chlorate clearance of CVVHDF approximates only 10% of total clearance in this case. CVVHDF may not produce significant reduction in the serum olprinone chlorate level. It is recommended that the infusion dosage of olprinone chlorate should be reduced when given to patients with renal failure even if treated with CVVHDF.     

Treatment of Graves' ophthalmopathy with cyclosporin A

Six patients with Graves' ophthalmopathy (2 with acute and 4 with chronic alterations) were treated with cyclosporin A (10 mg/kg/day) for 5 weeks. This treatment had no effect on either the ocular manifestations (protrusion, eye muscle function) or subjective well-being of the patients. In contrast, creatinine clearance decreased from 83.5 to 55.5 ml/min during treatment, but normalized (94.9 ml/min) after cessation of the drug. A transient increase in serum 4-androstenedione was observed in 3 patients. We conclude that cyclosporin A has no convincing effect in the treatment of Graves' ophthalmopathy, but rather exerts serious renal effects.     

Renal Blood Flow,Circulation Times and Vascular Volume in Normal Man Measured by the Intraarterial Injection —External Counting Technique

In six normal young men renal blood flow and renal mean circulation times for red cells and plasma were measured by external counting after injection into the renal artery of Xe-133, Cr-51 labelled red cells and 1–131 labelled albumin. Simultaneously the clearances of inulin and PAH and the blood pressure in aorta were measured. Inulin clearance was in average 122 ml/min. 1.73 m', PAH clearance 663 ml/min. 1.73 m², renal cortical blood flow 5.4 ml/g. min., mean renal blood flow 4.6 ml/g. min., mean circulation time for erythrocytes 4.7 sec., mean circulation time for plasma 5.5 sec. and mean blood pressure in aorta 89 mm Hg. The renal cortical vascular volume was 46 mli 100g. The data on renal blood flow obtained by the external counting technique correlated well with those obtained from the clearance measurements. The mean circulation times were shorter than those measured by other investigators using indicator dilution techniques. The cortical vascular volume, which includes the blood in the renal veins and arteries, was greater than previously found in animal kidneys.     

Renal autoregulation of blood flow and filtration rate in the rabbit

Electromagnetic flow techniques and inulin clearance were used to determine the autoregulatory capabilities of the rabbit kidney in vivo. Renal blood flow was measured in 13 animals over a renal perfusion pressure range of 40-110 mmHg. Normal renal blood flow averaged 3.2 +/- 0.3 ml.min-1.g kidney-1 and was efficiently autoregulated above a renal artery pressure of 75 mmHg. For every 10 mmHg renal pressure change above 75 mmHg renal blood flow changed only 0.96%. Renal perfusion pressure was reduced from 102 +/- 3 to 74 +/- 2 mmHg in six animals. Over this pressure range glomerular filtration rate was not significantly decreased and averaged 4.2 +/- 0.5 ml/min at high pressure compared to 4.0 +/- 0.5 ml/min at low perfusion pressure. Results show that the rabbit kidney autoregulates renal blood flow and glomerular filtration rate efficiently above 75 mmHg. This range of autoregulation compares well with the autoregulatory range of the dog. The results also show that in the autoregulatory range the rabbit and the rat appear to autoregulate with equal efficiency but that the rabbit kidney begins to autoregulate at a low perfusion pressure than the average of approximately 100 mmHg usually found in the rat.     

Nierenfunktion nach Infusionspyelographie

Zusammenfassung Glomeruläre Filtrationsrate (GFR=Inulin-Clearance), effektiver Nierenplasmastrom (RPF=PAH-Clearance), Diurese, osmolare Clearance und Natriumausscheidung wurden bei 25 Patienten mit normaler und unterschiedlich eingeschränkter Nierenfunktion infolge beidseitiger parenchymatöser Nierenerkrankungen nach Infusionspyelographie (Methylglucamin-Iothalamat) untersucht. Die Patienten wurden nach der Größe der GFR vor der Kontrastmittel (KM-) Infusion in Gruppen mit normaler (113,8±18,9 ml/min/1,73 m²), eingeschränkter (36,9±5,9 ml/min/1,73 m²) und stark eingeschränkter (11,1±4,2 ml/min/1,73 m²) Nierenfunktion eingeteilt.Die GFR änderte sich innerhalb von 2 Std nach Kontrastmittelinfusion bei den einzelnen Gruppen zwischen +2,4% und –12,4% des Kontrollwertes, wobei nur der Abfall bei eingeschränkter Nierenfunktion signifikant war. Der RPF fiel nicht signifikant zwischen 13,2% und 20,5%. Das Verhalten von GFR und RPF der einzelnen Gruppen wich statistisch nicht vom gemeinsamen Verlauf nach KM-Infusion ab. Die beobachteten Änderungen lagen in der methodischen und physiologischen Streubreite.Diurese, osmolare Clearance und Natriumausscheidung stiegen nach KM-Infusion bei normaler und eingeschränkter Nierenfunktion signifikant an. Das Ausmaß des Anstiegs war abhängig von der GFR. Es handelte sich um eine osmotische Diurese mit einer signifikanten Korrelation zwischen Urinfluß und osmolarer Clearance. Die Natriumausscheidung stieg infolge Abnahme der Natriumrückresorption signifikant an. Bei stark eingeschränkter Nierenfunktion kam es nicht mehr zu einer signifikanten osmotischen Diurese und Zunahme der Natriumausscheidung.

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Renal function after infusion pyelography

Summary The effect of infusion pyelography (meglumine iothalamate) on glomerular filtration rate (GFR), effective renal plasma flow (RPF), diuresis, osmolar clearance and sodium excretion was investigated in 25 patients with normal and reduced renal function. GFR was normal in 11 patients (113.8±18.9 ml/min/1.73 m²), moderately reduced (36.9±5.9 ml/min/1.73 m²) and severely reduced (11.1±4.2 ml/min/1.73 m²) in 7 patients, respectively.GFR was between mean +2.4% and –12.4% of control within 2 hours after infusion pyelography. The fall became significant only in patients with moderately reduced renal function. The decrease of RPF in the three groups was not significant between 13.2 and 20.5% of control. Changes of GFR and RPF in single groups did not differ statistically from the overall trend. The changes observed were within physiological variation range.Diuresis, osmolar clearance and sodium excretion increased significantly after infusion pyelography in patients with normal and moderately reduced renal function. The increase was in correlation with the GFR. The diuresis was osmotic, characterized by a significant correlation between urine flow and osmolar clearance. Tubular sodium rejection and urinary sodium excretion increased significantly. After infusion pyelography no significant osmotic diuresis and increase of sodium excretion occured in severely reduced GFR.

     

Renal blood volume regulation in trained and untrained subjects during immersion

Summary To study the cause of the increased blood volume of endurance-trained athletes we assessed the renal blood volume regulating mechanisms in eight untrained (UT) and eight endurance-trained (TR) male subjects during a 4 h head-out immersion. In TR plasma volume remained constant whereas it decreased in UT by 2.4 ml/kg (p<0.025). Immersion diuresis of TR was only half as high as in UT (peak values: 3.22 ml/min in UT, 1.60 ml/min in TR). Free water clearance remained approximately constant in UT but temporarily decreased in TR (p<0.001). This points to poor or even absent inhibition of antidiuretic hormone secretion in the latter group. Osmolar clearance increased less in TR than in UT (p<0.02) which was partly due to a delayed increase of glomerular filtration rate. Plasma osmolality, creatinine, and protein concentrations as well as hematocrit values were reduced during immersion to a similar extent in both groups. The results indicate a reduced renal response of endurance-trained subjects to congestion of the low-pressure system resulting in an increase in blood volume. A preliminary report was presented at the 45th meeting of the German Physiological Society [Pflügers Arch.359 (Suppl.), R 138 (1975)] Supported by the Minister für Wissenschaft und Forschung des Landes Nordrhein-Westfalen, Grant No. 06/0604/685 11