Interference therapy and radon baths in the combined treatment of patients with reflex cervicobrachial syndromes

Renal function was examined in 66 proteinura-free patients at the age of 40-67 years having diabetes mellitus (DM) type II for 4-10 years and HbA1c 7% maximum. Non-insulin-dependent DM was found to affect both glomerular and tubulointerstitial renal systems. This was indicated by reduced glomerular filtration, microalbuminuria, hyperenzymuria, high blood and urine levels of beta-2-microglobulin. Administration of glurenorm instead of maninil led to enhancement of glomerular filtration, lowerering of albuminuria, uroenyzmes, beta-2-microglobulin in the blood and urine. Glurenorm is a proper drug in DM type II as it has both sugar-reducing and nephroprotective effects.     

The significance of beta 2-microglobulin in diagnosis and therapy

This article describes the significance of beta 2-microglobulin (beta 2m) determination both in urine and serum for the estimation of proximal renal tubular function and glomerular filtration rate. The usefulness of beta 2m in therapy, cancer diagnosing, epidemiologic investigations of industrial exposure to cadmium, lead, mercury and in evaluating etiologic factors of environmental nephropathies was also discussed.     

Effects of gemcitabine on renal function in patients with non-small cell lung cancer

Gemcitabine is a novel fluorine-substituted cytarabine (Ara-C) analogue with activity against a range of solid tumours. Besides dose-limiting haematological toxicity, renal side-effects were observed from phase I and II studies concerning elevations of serum creatinine, proteinuria and erythrocyturia. The aim of this study was to investigate the effect of gemcitabine on renal function in 11 untreated patients with non-small cell lung cancer (NSCLC). Gemcitabine was given as weekly infusions of 1250 mg/m2 for 3 weeks, followed by 1 week rest. This comprised one cycle (maximum of six cycles). The glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were measured simultaneously with a constant infusion of 125I-iothalamate and 131I-hippuran, respectively. Tubular damage was monitored by excretion of tubular enzymes (lactic dehydrogenase (LDH), alkaline phosphatase (ALP), gamma-glutamyltransferase (GT) and beta 2-microglobulin); glomerular damage was monitored by excretion of albumin in the urine. In 9 patients, the effect of the first infusion was evaluated. After the first infusion of gemcitabine, no change was observed in renal function. After two, three, and six cycles of treatment, no significant changes in GFR and ERPF were noticed in 9 evaluable patients. However, in 3 patients, a decrease in GFR of > 10% was observed after multiple cycles. In one of them this was accompanied with albuminuria (360 mg/24 h) and erythrocyturia. There were no significant changes in urinary excretion of tubular enzymes or albumin. In conclusion, we did not observe acute renal toxicity with gemcitabine. No significant cumulative effects of gemcitabine on renal function could be detected, although 3 patients, treated with multiple cycles of gemcitabine, showed a moderate decrease in renal function. Glomerular damage might play a role in the development of renal function loss.     

Albuminuria and overall capillary permeability of albumin in acute altitude hypoxia

The mechanism of proteinuria at high altitude is unclear. Renal function and urinary excretion rate of albumin (Ualb) at rest and during submaximal exercise and transcapillary escape rate of 125I-labeled albumin (TERalb) were investigated in 12 normal volunteers at sea level and after rapid and passive ascent to 4,350 m. The calcium antagonist isradipine (5 mg/day; n = 6) or placebo (n = 6) was administered to abolish hypoxia-induced rises in blood pressure. Lithium clearance and urinary excretion of beta 2-microglobulin were used to evaluate renal tubular function. High altitude increased Ualb from 2.8 to > 5.0 micrograms/min in both groups (P < 0.05). In the placebo group, high altitude significantly increased filtration fraction (P < 0.05), but this response was abolished by isradipine. Lithium clearance and urinary excretion of beta 2-microglobulin remained unchanged by hypoxia in both groups. Exercise did not reveal any further renal dysfunction. In both groups, high altitude increased TERalb from 4.8 to > 6.7%/h (P < 0.05). In conclusion, acute altitude hypoxia increases Ualb despite unchanged tubular function and independent of effects of isradipine on filtration fraction. The elevated TERalb suggests an overall increase in capillary permeability, including the glomerular endothelium, as the critical factor in high-altitude induced albuminuria.     

Volume replacement solutions--pharmacology and clinical use

PHYSIOLOGY AND PATHOPHYSIOLOGY: Total body water represents 60% of body weight (BW), consisting of 40% BW intra- and 20% BW extracellular fluid. Extracellular fluid is divided into 16% BW interstitial fluid and 4% BW plasma volume (Fig. 1). The colloid oncotic pressure (COP) of the plasma proteins, which is about 25 mmHg (Fig. 2), is the main factor for the retention of intravascular volume and the prevention of interstitial edema. Within a defined range, oxygen transport capacity can be improved by normovolaemic haemodilution. Under strictly normovolaemic conditions ("controlled haemodilution"), the critical haemoglobin concentration for intensive care patients is about 10.0 g/dl, and 8-6 g/dl in patients with satisfactory compensatory mechanisms under stable clinical conditions. Larger blood volume deficits are replaced step by step with volume replacement solutions (crystalloids and synthetic colloids), packed red cells, fresh-frozen plasma, and platelets (Fig. 3). VOLUME REPLACEMENT WITH CRYSTALLOID AND COLLOID SOLUTIONS: Crystalloid solutions do not contain any macromolecules. Due to their lack of intrinsic COP, they spread rapidly over the intravascular and interstitial space. To achieve a comparable volume effect like colloid solutions, a fourfold infusion volume is necessary. Thus, crystalloids should be used in addition to colloid solutions to compensate the interstitial fluid deficit. Hyperosmotic-hyperoncotic solutions have not yet been established, and their benefit seems doubtful. Synthetic colloid solutions contain gelatin, dextran, or hydroxyethyl starch (HES) molecules. Due to their intrinsic COP, fluid is fixated in the intravascular space (Fig. 4). Solutions with high COP increase the intravascular volume due to resorption of interstitial fluid (plasma expanders). Pharmacological characterisation of synthetic colloids includes concentration [%], mean molecular weight [x1,000 Dalton] and degree and position of substitution (HES only). Main clinical features are the maximal volume effect and the duration of a 100% and a 50% volume effect (Fig. 5). For economic reasons, 5% albumin should not be used for volume replacement. The use of 20% albumin in intensive care patients is also limited and recommended only if a capillary leck is unlikely and the dose limits of synthetic colloids are reached. Gelatin is a polypeptide of bovine origin and achieves a shortlasting isovolaemic volume effect. When compared with dextran or HES, negative effects on haemostatis are less, and the renal function is not impaired. Thus, gelatin is first of all indicated in patients with limited volume demand, and secondly in situations with massive blood losses, when the dose limits of HES are reached. Dextran has no specific benefits. HES is a polysaccharide of maize or potato origin. By substitution of glucose molecules with hydroxyethyl groups, starch molecules are protected against fast amylase degradation. Metabolism depends on the degree and position of substitution and mean molecular weight. Smaller molecules are eliminated via the kidneys, but a certain amount of larger molecules is stored in the reticulo-endothelial system. HES is available in very different preparations (concentration 3-10%, mean molecular weight 70,000-450,000 Dalton, substitution 50-70%). Special indications of 10% HES 200/0.5 are rapid hypervolaemic replacement of massive blood losses and increase of COP in intensive care patients without capillary leak. Synthetic colloids as well as albumin may lead to adverse reactions, which are generally very rare. In large-scala studies, no significant differences have been found with regard to incidence and severity.     

Non-radioactive detection of K-ras mutations by nested allele specific PCR and oligonucleotide hybridization

PURPOSE: The aim of the study was to evaluate prospectively urinary alpha 1-microglobulin as a marker of proximal tubular damage following acute pyelonephritis and outflow disease of the upper urinary tract in a urological population with minimal exclusion criteria. We also measured the urinary gamma-glutamyltransferase activity, urinary albumin, urinary and serum creatinine, serum IgA and serum alpha 1-microglobulin. PATIENTS AND METHODS: We studied 483 urological patients (age: 1 to 92 years, 297 men, 186 women) excluding patients receiving nephrotoxic drugs, or suffering from type 1 diabetes or renal diseases. There were 141 patients with urinary tract infection but no fever, 36 patients with high fever of non-renal origin, 51 patients with acute pyelonephritis and 156 patients with outflow disease of the upper tract, and 99 patients were included in the reference population. RESULTS: For acute pyelonephritis, vesico-ureteral reflux, and ureteral obstruction, urinary alpha 1-microglobulin had a sensitivity of 94%, 90% and 63% respectively and a specificity of 67%, 77% and 76%. The area under the curve of the receiver operator characteristic curve was significantly (p < 0.001) higher for urinary alpha 1-microglobulin than for albumin or gamma-glutamyltransferase activity. Unexpected positive results were found in acute prostatitis. The urinary alpha 1-microglobulin was the only parameter which differentiated between acute prostatitis and pyelonephritis (p < 0.001). Creatinine clearance or age had little and gender had no influence on the urinary excretion of alpha 1-microglobulin. Urine production rate significantly increases the urinary alpha 1-microglobulin/creatinine ratio. CONCLUSION: Our results suggest that the urinary alpha 1-microglobulin/creatinine ratio is a diagnostically useful marker of tubular damage in acute pyelonephritis and vesico-ureteral reflux in the urological population. Following renal colic and chronic ureteral obstruction, a significant increase in urinary alpha 1-microglobulin excretion was observed.     

Elvin Semrad''s contributions to the everyday practice of psychotherapy

Sepsis is associated with altered blood rheology. Fluid infusion is an essential component of therapy for septic shock. The purpose of this study was to compare the rheologic changes associated with saline, albumin, and hydroxyethyl starch in sepsis. Whole blood was obtained from five normal controls and five patients with severe sepsis. The samples were centrifuged, and the erythrocytes were resuspended in autologous plasma or autologous plasma plus the buffy coat at an hematocrit (Hct) of 40%. The sample was diluted to an Hct of 30%, 20%, and 10% with saline, albumin, or hydroxyethyl starch. Viscosity was measured at low and high shear rates and erythrocyte aggregation was measured by the ratio of viscosity at low to high shear rates. Erythrocyte deformability was assessed by filtration. The viscosity of hydroxyethyl starch was greater than saline, albumin, or autologous plasma (p < .01). Erythrocyte viscosity was greater (p < .01) and deformability less (p < .01) in septic blood compared with normals. Dilution with hydroxyethyl starch increased erythrocyte viscosity as compared with saline (p < .01) and albumin (p < .01). Erythrocyte deformability was decreased with both hydroxyethyl starch (p < .001) and albumin (p < .05) compared with saline. Increased erythrocyte aggregation was also observed with hydroxyethyl starch (p < .05) and albumin (NS) in septic cells when compared with saline. These data indicate that hydroxyethyl starch increases blood viscosity, decreases erythrocyte deformability, and increases erythrocyte aggregation when compared with saline. These changes are less significant with albumin. In patients with sepsis, these effects may further compromise the already altered erythrocyte rheology.     

Glomerular filtration and tubular reabsorption of albumin in preproteinuric and proteinuric diabetic rats

Microalbuminuria (26-250 mg/d) is considered to be an indicator of incipient diabetic nephropathy in humans in insulin-dependent diabetes (IDD). However, before microalbuminuria is observed, glomerular alterations, such as glycosylation of the glomerular basement membrane and glomerular hyperfiltration, in IDD may result in increased filtration of albumin before any observed increase in albumin excretion. Glomerular and tubular albumin kinetics were examined in streptozotocin (65 mg/kg body wt, i.v.) diabetic, Munich-Wistar rats at 7-10 (untreated) and 50-70 d (poorly controlled with small doses of insulin) after the onset of diabetes and compared with nondiabetic controls. Additional rats in each condition received acute lysine treatment to prevent tubular protein reabsorption. Urinary albumin excretion and nonvascular albumin distribution volumes were measured in the renal cortex and compared with morphometric measurements of interstitial space and the proximal tubule to assess intracellular uptake of albumin in the proximal tubule. Urinary albumin excretion under anesthesia was not different in 7-10-d IDD versus controls (19 +/- 3 vs. 20 +/- 3 micrograms/min) but increased in the 50-70-d IDD (118 +/- 13 micrograms/min, P < 0.05). Lysine treatment resulted in increased albumin excretion compared with respective nontreatment in 7-10-d IDD (67 +/- 10 micrograms/min, P < 0.05) but not in controls (30 +/- 6 micrograms/min) or in 50-70-d IDD (126 +/- 11 micrograms/min). Glomerular filtration rate was increased both in 7-10-d IDD (2.7 +/- 0.1 ml/min, P < 0.05) and in 50-70-d IDD (2.6 +/- 0.1 ml/min, P < 0.05) compared with control (2.2 +/- 0.1 ml/min). Calculated urinary space albumin concentrations increased early in IDD with 2.5 +/- 0.4 mg% in 7-10-d IDD and 4.9 +/- 0.6 mg% in 50-70-d IDD compared with control (1.4 +/- 0.3 mg%). The increase in filtration of albumin is in excess of that attributable to hyperfiltration before increased albumin excretion early in diabetes. In 50-70-d IDD, absolute tubular reabsorption of albumin is decreased, correlating to the decrease in brush border height of the proximal tubule.     

Significance of the karyopyknotic index in the course control of hormone-treated prostatic carcinoma

Renal function was evaluated in 40 patients with fulminant hepatic failure, They were divided into two groups on the basis of glomerular filtration rates greater than 40 ml/min or less than 25 ml/min. A number of patients in group 1 had markedly abnormal renal retention of sodium together with a reduced free water clearance and low potassium excretion which could be explained by increased proximal tubular reabsorption of sodium. The patients in group 2 had evidence that renal tubular integrity was maintained when the glomerular filtration rate was greater than or equal ml/min (functional renal failure), but evidence of tubular damage was present when this was less than 3 ml/min (acute tubular necrosis).     

Duplex (thermotroph-psychrotroph) quadrant plates: convenient, error-avoiding tools for monitoring of HACCP-contained food lines and for epidemiological investigations under conditions of military or other constraints

The present study evaluated whether chronically administered low-dose (<5 mg/kg) ciclosporin A (CsA) affects renal haemodynamics and tubular function in renal transplant recipients (RTx) when studied at nadir CsA blood levels. The renal clearance of lithium was used as an index of proximal tubular outflow of sodium and water. Effective renal plasma flow, glomerular filtration rate, and renal clearance of lithium were studied in 67 stable non-diabetic RTx and 44 healthy controls. Forty-eight of the RTx were treated with CsA, prednisone, and azathioprine. Nineteen were treated exclusively with prednisone and azathioprine. In RTx with a good graft function (serum-creatinine <125 micromol/l), no specific CsA-induced renal haemodynamic and tubular dysfunctions were evident. In CsA-treated RTx with a slightly reduced renal function (serum creatinine 125-180 micromol/l) a decrease in fractional proximal tubular reabsorption was found. The renal clearances of urate and magnesium were comparable between RTx treated with or without CsA, and a significant correlation between glomerular filtration rate and renal clearance of urate was found. CsA-treated RTx had a significantly higher blood pressure, independent of glomerular filtration rate and segmental tubular function. In conclusion, at nadir CsA blood levels, no specific CsA-induced tubular dysfunction evaluated by the renal lithium clearance method could be demonstrated in RTx receiving chronically low-dose CsA. The hyperuricaemia commonly seen in RTx seems to be mainly caused by the reduced glomerular filtration rate.     

Antibacterial activity of the derivatives of cholic acid (author''s transl)

Serum and urinary myo-inositol and urinary glucose were estimated by means of gas-liquid chromatography in 54 patients with glomerulonephritis with and without renal failure. myo-Inositol clearance was calculated and an index was formulated which reflected changes in glomerular filtration, tubular reabsorption and catabolism of myo-inositol by the kidney. Serum and urinary myo-inositol levels were increased in glomerulonephritis with a close correlation to the degree of renal failure. In advanced forms of glomerulonephritis, glomerular filtration, tubular reabsorption and catabolism of myo-inositol were shown to be markedly deranged. Evidence obtained showed further that a derangement of tubular reabsorption and catabolism of myo-inositol also accompany milder forms of glomerulonephritis without decreased glomerular filtration. The myo-inositol index value, especially, was increased in patients with signs of disease activity as indicated by a histological examination of the kidney tissue. The index can also be regarded as a highly sensitive test of renal failure. Low grade glucosuria was shown to be frequently associated with glomerulonephritis with renal failure. Evidence was produced which suggested that the tubular reabsorption of myo-inositol was deranged earlier than glucose reabsorption in glomerulonephritis, although they may share a common step in the reabsorption process. The data suggest that the estimation of serum and urinary myo-inositol has advantages in the evaluation of kidney function.     

Physiopathology of proteinuria and laboratory diagnostic strategy based on single protein analysis

A quantification of proteins of different molecular size has been shown to be useful in characterizing the mechanism and medical causes of proteinuria. By analyzing urine albumin, alpha1-microglobulin, immunoglobulin G and alpha2-macroglobulin together with total protein, prerenal, glomerular, tubular and postrenal causes of proteinuria can be detected and differentiated by their specific urine protein patterns. Using automated turbidimetric procedures, prerenal proteinurias are characterized by an albumin/total protein ratio below 0.4. Tubulo-interstitial diseases which are negative in the protein test strip procedure are detected and clearly differentiated from other causes of proteinuria by their high alpha1-microglobulin/albumin ratios. In post-renal proteinuria, alpha2-macroglobulin proved to be a useful marker, when albumin excretion exceeds 100 mg/l urine. This protein exhibits plasma-like ratios to albumin in postrenal causes, whereas it is much lower in renal proteinurias. The new strategy, which has been evaluated in more than 500 clinically and partly histologically proven cases of renal diseases, more sensitively detects glomerular and tubulo-interstitial diseases when applied in urine screening and allows us to distinguish all clinically important causes from analysis of a morning spot urine sample.     

Selective planting of cationized, haptenized ovalbumin on the rat tubular basement membrane

We developed an experimental protocol for planting exogenous antigens with different molecular weights and charges on the constituents of the renal tubulointerstitium. The cationized antigens were injected selectively into the left renal arteries of Wistar rats. Antigen localization was documented by immunohistochemistry on frozen sections. Cationized bovine serum albumin (BSA; 68 kDa, isoelectric point = 9.5) localized almost exclusively along the glomerular capillary wall. After application of highly cationic polyethyleneimine, cationized BSA given subsequently was found in a linear distribution along the glomerular capillary wall and along the peritubular capillaries. The fate of highly cationized ovalbumin conjugated with trinitrophenol (TNP-OA), subjected to gel filtration to obtain monomers (42 kDa, isoelectric point > 10) differed; it was deposited in a linear pattern on the tubular basement membrane (TBM) and Bowman's capsule, and remained up to 36 h after injection. Noncationized, monomeric TNP-OA (42 kDa, isolectnic point = 4.6) showed fine granular deposition in the tubular epithelium exclusively. These findings indicate that the barrier of the glomerular BM acts selectively on antigens with different molecular weights. They either settle on the peritubular capillaries, after passing the glomerular, or reach the urinary space, after which they are reabsorbed by the tubular epithelial cells to reach the TBM.     

Evaluation of highly damaged renal function following extracorporeal circulation--usefulness of alpha 1-microglobulin index

The patients with highly damaged renal functions following extracorporeal circulation (ECC) were reviewed. Markers such as serum and urine creatinine (SCr, UCr), blood urea nitrogen (BUN), alpha 1-microglobulin in urine (as a marker of renal tubular function, abbreviated as U alpha 1-m), microalbumin in urine (as a marker of renal glomerular function, abbreviated as UA1b) were measured in each cases. Twenty patients were selected with the maximum value of U alpha 1-mover 60 micrograms/dl during or after ECC. The patients were classified into three groups according to preoperative value of alpha 1-m index (alpha 1-m index (I) = U alpha 1-m/UCr x 100 mg/g Cr), and Albumin index (Albumin index (I) = UA1b/UCr x 100 mg/g Cr). Group I (n = 13); alpha 1-m I > 10 and, Alb I > or = 50 (abnormal value of tubular and glomerular function), Group II (n = 3); alpha 1-m I < or = 10, Alb I > or = 50 (abnormal value of glomerular function), Group III (n = 4); alpha 1-m I < or = 10, Alb I < 50 (normal value of tubular and glomerular function). Six patients in Group I required postoperative hemodialysis (HD) and one patient in Group II. No one required HD in Group III. These facts suggest that preoperative damage of tubular and glomerular functions may become prolonged or irreversible damages may occur after operation. HD is required frequently in patients with alpha 1-m I level over 500 mg/g Cr, especially continuous HD may be needed in patient with alpha 1-m I level over 1000 mg/g Cr.     

The impact of a national impregnated bed net programme on the outcome of pregnancy in primigravidae in The Gambia

The effect of the non-ionic contrast medium iohexol (Omnipaque) on renal function was investigated in diabetic patients with signs of peripheral ischaemia. Forty-six patients, 70 +/- 11 years (mean +/- SD) old, age at diabetes diagnosis 53 +/- 17 years, and with varying degrees of diabetic nephropathy were studied before 1, 2, and 30 days after aortobifemoral arteriography. Serum creatinine, creatinine clearance, urinary excretion of immunoglobulin G, albumin collagen IV (NC1), kappa and lambda chains, alpha-1 microglobulin and Tamm-Horsfall protein were evaluated. Within 1 month before and 30 days after arteriography, the glomerular filtration rate was measured by clearance of iohexol. The acute effect of the radiocontrast medium was an increase in the serum creatinine level in 41 (89%) patients, with a more than 25% increase in 12 (26%) patients. The excretion rates of immunoglobulin G and albumin decreased, whereas the proximal and distal tubular function and the excretion of collagen IV did not change. The increment in serum creatinine was associated with the preangiographic renal function (p < 0.05), a history of heart failure (p < 0.01), but not with age, duration and type of diabetes, gender, systolic or diastolic blood pressure, glycated haemoglobin (HbAlc) or blood glucose levels. The increase of serum creatinine was associated with a pre-existing proximal tubular dysfunction and a worsening of distal tubular function. No changes in the parameters measured persisted 30 days after angiography. In summary, a transient increment in serum creatinine level after arteriography occurred in 89% of diabetic patients. It was associated with the preangiographic renal function, a history of heart failure and signs of preexisting proximal tubular dysfunction and worsening of distal tubular function. However, these changes were reversible.     

A prospective study of the length of stay of 150 children following tonsillectomy and/or adenoidectomy

In glomerular diseases the filtration of excess proteins into the proximal tubule, together with their subsequent reabsorption may represent an important pathological mechanism underlying progressive renal scarring. The most prominent protein in glomerular filtrate, albumin, is reabsorbed by receptor-mediated endocytosis by proximal tubular cells. It binds both to scavenger-type receptors and to megalin in the proximal tubule. Some of these receptors appear to be shared with other cell types, particularly endothelial cells. The endocytic uptake of albumin is subjected to complex hormonal and enzymatic regulation. In addition to being reabsorbed in the proximal tubule, albumin may act as a signalling molecule in these cells, and may induce the expression of numerous pro-inflammatory genes. Modulation of the interaction of albumin with proximal tubular cells may eventually prove to be of therapeutic importance in the treatment of renal diseases.     

Effect of antihypertensive treatment on urinary albumin excretion, glomerular filtration rate, and renal plasma flow in patients with essential hypertension

In 20 patients with essential hypertension the urinary albumin execretion, glomerular filtration rate (GFR),and renal plasma flow (RPF) were examined before and after antihypertensive treatment. Albumin excretion measured by radioimmunoassay was increased before treatment, and there was a significant fall during treatment. In patients responding well to therapy (diastolic pressure below 100 mm Hg), albumin excretion was significantly lower than in patients responding poorly to therapy. There was a positive correlation between albumin excretion before treatment and diastolic pressure during treatment, indicating that the albumin excretion rate may be used to predict the result of antihypertensive treatment. Patients with excretion rates below 25 mug/min generally respond well to the treatment used. No definite changes in GFR and RPF were found during treatment, and there was no correlation between albumin excretion and GFR and RPF. It is suggested that the increased albumin excretion in essential hypertension is due both to functional and morphological alterations in the glomerulus, namely increased glomerular filtration pressure and vascular damage.     

The effects of an angiotensin blocker (saralasin) on kidney function in dehydrated sheep

Saralasin, an angiotensin II analogue and receptor blocker, was infused at 7 and 15 micrograms . min-1 into dehydrated conscious Merino ewes. This caused mean arterial blood pressure, cardiac output, heart rate and renal vascular resistance to fall, and central venous pressure to rise. Renal plasma flow was unaffected but there were significant reductions in glomerular filtration rate, filtration fraction, urine flow, sodium and potassium excretion, solute clearance and solute-free water reabsorption. It is suggested that saralasin produced these effects by inhibiting endogenous angiotensin II activity, and in particular by causing a reduction in renal post-glomerular resistance. This in turn caused a fall in glomerular filtration rate and filtration fraction. While saralasin might have had effects on renal tubular function and perhaps on vasopressin secretion, the observed effects on renal function can be explained by the decrease in glomerular filtration rate and filtration fraction.     

The pharmacokinetics of acetyl starch as a plasma volume expander in patients undergoing elective surgery

Acetyl starch (ACS) is a new synthetic colloid solution for plasma volume expansion and is now undergoing phase 2 clinical trials. We compared the pharmacokinetics of ACS with those of hydroxyethyl starch (HES) in 32 patients (ASA physical status I and II) undergoing elective surgery. In this randomized, double-blind trial, patients received either 15 mL/kg ACS 6% (average molecular weight [Mw] 200,000/molar substitution [MS] 0.5) or HES 6% (Mw 200,000/MS 0.5) i.v. up to a maximal dose of 1000 mL. Plasma colloid concentrations were measured by repetitive arterial blood sampling over 24.5 h. Plasma colloid concentrations were detected using a high-pressure liquid chromatography controlled enzymatic test. Standard pharmacokinetics were calculated, including initial half-life (t(1/2init)), i.e., the time required for a 50% decline of the maximal plasma colloid concentration at the end of drug infusion. Whereas HES was eliminated by second-order kinetics, ACS followed first-order characteristics. In the first hours after i.v. administration, t(1/2init) and clearances were similar in both groups. However, the terminal half-life of HES was significantly longer than that of ACS (9.29 +/- 1.43 h vs 4.37 +/- 1.06 h). After 16.5 and 24.5 h, ACS showed significantly lower plasma concentrations than HES, which indicates that the final degradation of ACS by esterases and amylase was significantly more rapid. ACS might be an alternative plasma volume expander, which avoids the accumulation of persisting macromolecules. Implications: We studied the pharmacokinetics of acetyl starch, a newly developed colloid solution for plasma volume substitution, compared with hydroxyethyl starch in 32 surgical patients undergoing elective major general surgical procedures. In contrast to hydroxyethyl starch, this new agent undergoes rapid and nearly complete enzymatic degradation.     

Role of endothelin in the development of glomerulosclerosis

Enhanced filtered load of proteins in glomerular diseases (overload proteinuria) results in significant increase in the rate of proximal tubular uptake that is true for all proteins tested so far, including albumin. The excess concentration of absorbed proteins in lysosomes may itself lead to cellular damage by spillage of lysosomal enzymes to the cytosol. In vitro evidence is also available of functional alteration of these tubular cells, including upregulation of genes encoding for endothelin-1 (ET-1) and other inflammatory mediators, when they are overloaded in culture with proteins or lipoproteins. This could affect renal function and structure given the inflammatory, growth factor, and vasoactive properties of ET-1. Findings in several experimental models of proteinuric progressive nephropathies have indeed documented enhanced renal ET-1 gene expression and excretion of the peptide into the urine which correlated with proteinuria and the degree of glomerular and tubulointerstitial damage.