Familial benign hypercalcaemia: a possible abnormality in calcium transport by erythrocytes

Abstract. The fundamental biochemical abnormality in familial benign hypercalcaemia (FBH) (familial hypocalciuric hypercalcaemia) is unknown. It seemed possible that, since the kidneys and the parathyroid glands are insensitive to the high extracellular calcium levels, a general disorder of the regulation of the calcium pump on the plasma membrane is present. We obtained evidence suggesting that active calcium efflux by erythrocytes from patients with FBH (85·7 pL 4·5 μmol l^-1 min^-1) is higher ( P < 0·005) than that by erythrocytes from control subjects (78·6 pL 4·1 μmol l^-1 min^-1) or from patients with primary hyperparathyroidism (77·5 pL 5·2 μmol l^-1 min^-1, P < 0·05). Calcium influx into erythrocytes was normal in FBH and in primary hyperparathyroidism.     

Effects of insulin-like growth factor-I (IGF-I), insulin and combined IGF-I-insulin infusions on protein metabolism in dogs

Abstract The effect of infusions of recombinant insulin-like growth factor-I (IGF-I) (34, 103 or 688 pmol min^-1 kg^-1), insulin (3·4, 10·3 or 68·8 pmol min^-1 kg^-1) or combined infusions (34 pmol IGF-I+ 3·4 pmol min^-1 kg^-1 insulin or 103 pmol IGF-I+ 3·4 pmol min^-1 kg^-1 insulin) on protein metabolism, using an infusion of [1-¹⁴C] leucine was investigated in anaesthetized fasted dogs. Leucine concentration, production rate (measure of protein degradation), oxidation rate and non-oxidative disappearance rate (measure of protein synthesis) were decreased in a similar dose dependent manner by the IGF-I and insulin infusions (P <0·01). The decrease in these measurements of leucine metabolism were greater following 34 pmol IGF-I + 3·4 pmol insulin than with either component infused alone (P <0·05). Free fatty acid concentrations were decreased by all insulin doses (P < 0·01) but only by 103 and 688 pmol min^-1 kg^-1 insulin-like growth factor (P < 0·05, P < 0·01). These data demonstrate that IGF-I, like insulin, has a dose dependent effect on protein metabolism and that combined insulin and IGF-I infusions have additive effects on protein metabolism.     

Kinetics of circulating hyaluronan in humans

Abstract The elimination of intravenously injected hyaluronan (HA) from the blood was investigated in 12 healthy volunteers. Three consecutive 30 min infusions of HA were given, separated by 90 min washout periods. Blood samples were taken before, during and after each infusion and the plasma HA concentration was determined. The deposition of HA was modelled according to a Michaelis–Menten kinetic model which included natural synthesis of HA. K_m and V_max was estimated to 0·34 ± 0·13 μgml^-1 and 3·48 ± 0·97/μmin^-1kg^-1 b.w., respectively. The endogenous input was calculated to be 24 ± 11 μg min^-1 and was found to correlate to the age of the subjects ( P < 0·05). As the baseline HA concentration was 0·031 ± 0·21 μg ml^-1, the rate of elimination was linear in the normal concentration range. The calculated V_d was about 75% higher than a weight-estimated plasma volume. The total amount of HA excreted by the kidneys during the study period was 394 ± 77 μg, which corresponded to approximately 1·7% of the total input of HA into the circulation during the experiment.     

The individual variation in pharmacokinetics and pharmacodynamics of furosemide in young normal male subjects

Abstract. Following a 24 h control period in the ward 80 mg furosemide was injected intravenously to ten young healthy, male volunteers. The serum clearance of furosemide (Cl_s) was between 140 and 201 ml min^-1 and on the average the renal clearance was 66% of Cl_s. During the initial 30 min period a maximum additional excretion rate of sodium of 3·3 mmol min^-1 was reached at an excretion rate of 0·8 mg furosemide min^-1. A marked initial drop in creatinine clearance (Cl_cr) was noted and Cl_{cr(24 h)} showed an average decrease of 12% after the drug administration. The serum concentration of potassium was decreased at 1 and 2 h after the injection and of sodium from 2 h and on. The concentration of albumin in serum increased by 3% ( P < 0·05) already after 5 min. After 2 h a maximum increase of 14% was reached. After 8 min diastolic blood pressure was increased by 13% ( P < 0·05), whereas systolic blood pressure reached a significant decrease gradually (7% after 3 h).     

Time course of haemodynamic changes after maximal exercise

Abstract. The haemodynamic changes during 4 h following maximal upright bicycle exercise were evaluated in six normals in a randomized controlled crossover design. Total peripheral resistance was reduced to 2 h (-6·7 mmHgmin l^-1, P < 0·05); exercising and non-exercising vascular beds were vasodilated for 2h (-24·1 and -23·8 mmHg min ml^-1 100ml^-1 tissue, respectively, P < 0·05), associated with reductions in systolic (-5·8 mmHg, P < 0·05) and diastolic pressure (-8·3mmHg, P < 0·05). Rise in cardiac index for 1 h (+0·51min^-1 m^-2, P < 0·05) was accounted for by an elevated heart rate (+14·4 beats min^-1, P < 0·01) as stroke volume was unchanged. Body temperature was elevated until 40min (+0·20°C, P < 0·05). The return of all haemodynamic variables to control by 3h suggests a 3 h limit for a hypotensive effect of exercise. Rise in body temperature is not the only factor responsible for the hypotension.     

Tubular site of renal sodium retention in ascitic liver cirrhosis evaluated by lithium clearance

Abstract. Renal tubular sodium handling was evaluated in 27 non-azotemic cirrhotic patients with ascites and positive sodium balance and in 17 controls after at least 5 days of a constant sodium intake using the lithium clearance as an index of fluid delivery to the distal tubule. Plasma renin activity and plasma aldos-terone were also evaluated. Sodium fractional excretion, filtered sodium load, absolute sodium distal delivery, lithium fractional excretion and absolute distal sodium reabsorption were significantly lower in cirrhotics than in controls (0.58 ± 0.11 vs. 1.29 ± 0.12%, < 0.001; 12529± 677 vs. 15707±796 μEq min^-1 1.73 m^-2 BSA, <0.005; 2384±135.2 vs. 3685±219.3 μEq min^-1 1.73 m^-2 BSA, < 0.001; 19.5±1.0 vs. 24.2±l.3%, < 0.01; 2299±127 vs. 3485±214 μEq min^-1 1.73 m^-2 BSA, <0.001, respectively). A correlation was found between lithium clearance and sodium clearance only in cirrhotic patients ( r = 0.62; <0.01). Distal sodium reabsorption evaluated as a per cent of filtered sodium load was lower in cirrhotics than in controls (19.1 ±1.0 vs. 22.4±1.2%, <0.05) while distal sodium reabsorption evaluated as a per cent of sodium distal delivery was higher in cirrhotics than in controls (96.7 ± 0.4 vs. 94.4± 0.5%,< 0.005). In both groups a correlation was found between log plasma aldosterone and distal sodium reabsorption evaluated as a per cent of absolute sodium distal delivery ( r = 0.61, <0.01 and r =0.52,<0.05 respectively).
Our study indicates that a decrease in filtered sodium load and an increase in proximal sodium reabsorption play a critical role in the impairment of renal sodium handling in non-azotemic cirrhotic patients with ascites.     

The pharmacokinetics of porcine glucose-dependent insulinotropic polypeptide (GIP) in man

Abstract. The pharmacokinetics of porcine glucose-dependent insulinotropic polypeptide were investigated in six healthy volunteers. At the maximum infusion dose (0·5 pmol kg^-1 min^-1) a plateau concentration of 115 ± 5·0 pmol/l plasma was obtained. On discontinuation of the infusion, the half-time of disappearance was calculated to be 20·3 ± 1·2 min. The metabolic clearance rate was 2·6 ± 0·1 ml kg^-1 min^-1 and the apparent space of distribution was 75·8 ± 5·7 ml kg^-1. Blood glucose, pancreatic and gastrointestinal hormones remained at basal concentrations throughout. No side effects were noted by any of the subjects studied.     

Protoporphyrinogen oxidase and porphobilinogen deaminase in variegate porphyria

Abstract. Two enzymes of the haem biosynthetic pathway were investigated in patients with variegate porphyria. Protoporphyrinogen oxidase in cultures of Epstein-Barr virus transformed lymphoblasts from twenty-seven patients showed a mean maximal velocity ( V _max) of 0·39 ± 0·08⁺ nmol of protoporphyrin mg protein^-1 h^-1, a 52% reduction ( P < 0·001) from a non-porphyric control group (0·82 ± 0·10). K _m values (1·00 ± 0·27 μ M) did not differ significantly ( P > 0·05) from control values in any of the patients. The mean V _max of porphobilinogen deaminase in the cultures was 1·50 ± 0·18 nmol of uroporphyrin mg protein^-1 min^-1, a 24% reduction ( P < 0·001) from controls (1·94 ± 0·14). Mean porphobilinogen deaminase activity in the erythrocytes of twenty-one patients with variegate porphyria was 8·37 ± 1·99 nmol of uroporphyrin 1 erythrocytes^-1 s^-1, a 28% reduction ( P < 0·001) from normal (11·98 ± 2·11). The reduced activities of these two enzymes comply with the expression of variegate porphyria during its quiescent and acute phases.     

Smoking attenuates the vasoconstrictor response to noradrenaline in type I diabetic patients and normal subjects: possible relevance to diabetic nephropathy

Abstract Exaggerated vascular reactivity has been implicated in the pathogenesis of diabetic nephropathy, and several studies suggest that smoking accelerates its progression. We therefore assessed the vasoactive effects of smoking by comparing noradrenaline-induced vasoconstriction in dorsal hand-veins between smoking and non-smoking groups of Type I diabetic patients with and without microalbuminuria and in non-diabetic subjects. Smokers had a significantly higher dose causing 50% vasoconstriction (reduced sensitivity to noradrenaline) in all three groups: microalbuminuric diabetic smokers vs. non-smokers, 20·2(4·6) (SEM) vs. 6·6(2·3) ng min^-1 (P = 0·02); normoalbuminuric, 76·9(29·4) vs. 22·8(9·1) ng min^-1 (P = 0·03); non-diabetic subjects, 97·8(30·0) vs. 38·0(12·8) ng min^-1 (P = 0·01). Both microalbuminuric diabetic groups showed significantly greater sensitivity to noradrenaline-induced vasoconstriction than the other smoking and non-smoking groups, respectively (P<0·01).
Vasoconstrictor responses to noradrenaline are attenuated in smokers, possibly due to α-adrenoceptor down-regulation. Smoking could increase urinary albumin losses and accelerate renal damage through catecholamine surges which raise systemic and, perhaps, intraglomerular blood pressure. This hypothesis deserves further consideration.     

Effect of long-term starvation on acetate and ketone body metabolism in obese patients

Abstract. The turnover of ketone bodies and acetate was evaluated as well from the disappearance rate of (3-¹⁴C)acetoacetate or (1-¹⁴C)acetate respectively as from the conversion of FFA into these metabolites in normal weight and obese overnight-fasted and in obese long-term starved patients. The disappearance rate of (1-¹⁴C)oleate was the same in all three groups.
Long-term starvation enhanced ketone body turnover almost 10-fold, whereas the disappearance rate for ketone bodies decreased from 0·035 to 0·015 min^-1. Under the same circumstances the turnover of acetate was about 1 μmol g^-1 min^-1 accounting for about 5% of FFA turnover.
Long-term starvation decreased the conversion of (1-¹⁴C)oleate into triglycerides by almost 50% and increased the (2-C)-(4-C)/(1-C) ratio of radioactivity in ketone bodies. The reincorporation of radioactivity from the (1-C)position of (1-¹⁴C)oleate into the ((2-C)-( n -C)) position of FFA, which is a measure of the reutilization of acetyl-CoA for FFA synthesis decreased significantly during long-term starvation.     

Hypotensive and renal effects of Captopril

Abstract. The effects of Captopril on blood pressure and renal function were evaluated in ten patients with different degrees of hypertension. In seven, blood pressure was reduced after 7 weeks of therapy; in three it remained practically unchanged. No correlation was found between the standing plasma renin activity before treatment and the hypotensive response. Plasma renin activity increased significantly from the median value of 5.4 (range 1–16.7) to 9.5 (range 2.6–19.8)ngml¹ h¹ (P< 005) and urine aldosterone significantly fell from 13 (range 2–3–52–5) to 7.4 (range 1.6–14) μg 24 h^-1 (P<001) during therapy. Renal plasma flow decreased from 534 (range 300–616) to 471 (range 333–606) ml min^-1, but the difference was not significant, and glomerular filtration rate fell significantly form 122 (range 64–143) to 88 (range 71–116) ml min^-1 (P<0–05). No urinary excretion of alpha₂-macroglobulin was observed during Captopril. 24 h proteinuria, albumin and transferrin clearance, alanine-amino transferase, gammaglutamyl transfer-ase and alpha glucosidase excretion rate and malate-dehydrogenase clearance remained unaltered throughout the treatment. This indicates that neither glomerular permeability nor renal tubular function were affected by the drug.     

Erythropoietic activity and iron metabolism in autologous blood donors during recombinant human erythropoietin therapy

Abstract. The use of recombinant human erythropoietin (rhEPO) to intensify the erythropoietic response in autologous donors may reduce homologous blood requirement. We studied the effect of subcutaneous rhEPO (500 U kg^-1 body weight twice weekly during a 3 week period) on variables of erythropoiesis and iron metabolism in 62 autologous blood donors, of whom 32 received rhEPO (epo group) and 30 did not (control group). Patients donated only 2 units of blood and received oral iron in order to restrict phlebotomyinduced decrease of iron stores. Pre-phlebotomy haemoglobin concentration (14·0±0·8 g dl^-1) was completely regenerated in the epo group at surgery (13·7±1·3 g dl^-1); haemoglobin concentration in the control group fell from 13·5±1·4 g dl^-1 to 11·6±1·4 g dl^-1 after the phlebotomies and did not improve during the pre-operative phase. Total erythropoietic activity expressed as serum transferrin receptor concentration (sTfR) showed a 4-fold increase from 3·8±0·9 μ g ml^-1 to 14·9±4·8 μ g ml^-1 in the epo group. Effective erythropoietic activity measured by absolute reticulocyte count, however, declined after the fourth rhEPO injection in the epo group. Serum ferritin was lower in the epo group, but no differences in serum iron, transferrin concentration and transferrin saturation were observed between the groups. A marked increase in free erythrocyte protoporphyrin (FEP) was observed in the epo group, whereas FEP levels in the controls remained within normal ranges. Despite oral iron supplementation and the limited number of phlebotomies, the effect of rhEPO therapy in autologous donors is restricted by iron depletion.     

Triglyceride metabolism in human liver: studies on hepatic phosphatidic-acid phosphatase in obese and non-obese subjects

Abstract. According to current concepts, soluble phosphatidic-acid phosphatase, converting phosphatidic acid into a diglyceride, is a rate-limiting enzyme in the hepatic biosynthesis of triglycerides. The present paper is the first report on this enzyme in human liver. The enzyme activity was assayed in ammonium sulphate precipitates of cytosol obtained from human liver biopsies. The activity was stimulated by preincubation with alkaline phosphatase and inhibited by Mg-ATP, suggesting that phosphorylation-dephosphorylation may be of some importance for the expression of the activity of the enzyme. When assayed under optimal conditions, the activity obtained in liver biopsies from normal-weight gallstone patients averaged 12·8 ± 2·0 nmol min^-1 (mg protein)^-1 (mean ± SEM) ( n = 17). The enzyme activity was slightly higher in liver biopsies from morbidly obese subjects 16·4 ± 2·8 nmol min^-1 (mg protein)^-1 ( n = 14). The difference between the two groups of subjects was probably in part sex-dependent and was not statistically significant. A similar small and insignificant difference between the two groups of subjects was found when the enzyme activity was assayed in the maximally stimulated state—i.e. after incubation with alkaline phosphate.
These findings suggest that an increased capacity of the soluble phosphatidic-acid phosphatase is not of major importance for the increased triglyceride synthesis known to occur in obesity. Other factors (i.e. availability of substrate and cofactors) may be of greater importance.     

A study of factors governing fluid filtration in the diabetic foot

Abstract. The effect of lowering the foot on the factors governing fluid filtration in the foot were studied in 12 male insulin-dependent diabetic subjects and 10 controls. Toe skin blood flow, measured by laser Doppler flowmetry, was significantly higher during dependency in the diabetic group. In the control subjects, the colloid osmotic pressure of venous blood sampled from the foot rose to 47·7 mmHg (range 45·1–53·8) after 50 min of foot dependency. In the diabetic group, colloid osmotic pressure failed to rise to the same extent (median 36·7 mmHg; range 28·6–43·0; P < 0·001). Capillary pressure, measured directly by the Landis microinjection technique, was significantly higher in the diabetic group (85·3±1·7 ( n = 6) vs. 92·2±4·6 cm H₂O ( n = 6); P < 0·007), as was foot swelling rate determined by mercury strain gauge plethysmography (0·069±0·022 vs. 0·099±0·025 ml min^-1 100ml^-1; P < 0·02). These results suggest an impairment of the oedema-preventing mechanisms in diabetic subjects which may contribute to the risks of ulceration in the diabetic foot.     

Seeking clues for a positive diagnosis of the irritable bowel syndrome

Abstract. Despite its high prevalence the irritable bowel syndrome (IBS) lacks acceptable pathophysio-logical markers and its diagnosis largely depends on the exclusion of underlying organic disease. Systemic acid-base balance, serum electrolytes and the composition of faecal water (electrolytes and organic anions), were studied in thirty-eight diarrhoeal patients out of a series of ninety-three consecutive IBS patients. Only patients with diarrhoea as the predominant symptom were included in the study to evaluate whether this subgroup could provide the clue for a positive diagnosis of the syndrome. Serum electrolytes and systemic acid–base balance were within the normal range. Faecal electrolytes were also normal (Na 26·6 pL 19·3 SD; K 66·8 pL 28·3; Cl 19·1 pL 15·2 mEq l^-1), despite the finding of a moderately increased 24-h faecal output. The K: Na ratio was also within the normal range. These data are in agreement with the lack of systemic changes observed in IBS patients even with profuse or longstanding diarrhoea. Both faecal short chain fatty acids and lactic acid were increased in patients vs. controls, but a considerable overlap with normal values was observed (131·4 pL 62·6 SD vs. 108·5 pL 58·3 mEq l^-1). Only lactic acid concentration was significantly higher than in controls (1·3 pL 1·2 vs. 0·5 pL 0·2). Despite these findings it is concluded that the subgroup of IBS patients with diarrhoea also appears to lack a pathophysiological marker and does not provide clues for a positive diagnosis of this syndrome.     

Metabolic clearance rate of immunoreactive vasopressin in man

Abstract. Metabolic clearance of synthetic arginine vasopressin (AVP) has been measured in sixteen healthy subjects and ten uraemic patients on maintenance haemodialysis. Plasma AVP was measured using a specific radioimmunoassay at different intervals after a single injection of 2 μg AVP. The theoretical curve which fitted best with the disappearance curve was the sum of two exponentials in twenty-two subjects and of three exponentials in the other four. Metabolic clearance rate and the volume of fast initial distribution were 287·1 ml min^-1 (m²)^-1 and 219·3 ml/kg b.w., respectively, in normal subjects. Metabolic clearance rate was considerably lower in the uraemic group. This emphasizes the role of kidneys in the degradation of AVP and may account, at least in part, for the higher basal plasma value of this hormone observed in uraemic patients.     

Effect of activation of protein kinase A and of protein kinase C on the kinetics of the renal basolateral PAH transporter

Summary— The aim of the present study was to examine the effect of activation of the protein kinase A (PKA) and protein kinase C (PKC) pathways on ³H-p-aminohippurate (PAH) uptake of isolated S₂ segments of proximal tubules, microdissected from rabbit kidneys without the use of enzymatic agents. Because the tubules were not perfused, and hence were collapsed, the tubular uptake of ³H-PAH reflects transport across the basolateral membrane. The phorbol ester phorbol 12-myristate 13-acetate (PMA) (10 ⁷ M), an activator of PKC, significantly increased tubular ³H-PAH uptake with steady state conditions (by 115%), whereas dibutyryl cyclic adenosine monophosphate (db-cAMP) (10^-4 M) and forskolin (10^-4 M) significantly inhibited it (by 42% and 52%, respectively). Kinetic data, which were based on 15 sec PAH uptake measurements, revealed that PMA, after a 10 min incubation period, significantly enhanced Km and Vmax of the PAH transporter (Km from 174 ± 22 to 447 ± 91 μM, Vmax from 2.76 ± 0.24 to 16.67 ± 1.85 pmol nL^-1 min^-1), whereas db-cAMP significantly decreased Vmax (from 2.76 ± 0.24 to 1.82 ± 0.19 pmol nL^-1 min^-1). The Km value was also numerically lowered by dibutyryl-cAMP (from 174 ± 22 to 139 ± 21 μM), but this change did not reach statistical significance. The data provide evidence that short time activation of the PKC pathway 1) enhances the effectiveness of PAH transport into proximal S₂ segments across the basolateral cell membrane, 2) increases the maximum transport rate of the PAH transporter and 3) decreases its affinity for PAH. Activation of the cAMP/PKA pathway induces the opposite effects.     

Effects of cyclooxygenase inhibitors, prostaglandins F2α and I2, on isolated coeliac and basilar arteries of alloxan-diabetic dogs

Abstract. The effects of prostaglandin synthetase inhibitors PGF_2α and PGI₂ on the tone of isolated basilar and coeliac arteries were studied in healthy and alloxan-diabetic dogs. PGF_2α (1 μmol l^-1) produced a significantly higher tone in diabetic basilar arteries (1·15 ± 0·16 mN) than in normal cerebral vessels (0·7 + 0·10 mN). By contrast, the contractile responses of normal and diabetic coeliac arteries to PGF_2α did not differ. The cyclooxygenase inhibitors indomethacin (3 μmol l^-1) and suprofen (0·58 μmol l^-1) potentiated the PGF_2α-evoked contractions in all of the vessels studied. The percent potentiation was greater (50–60%) in the basilar arteries from alloxan-treated dogs than in normal basilar vessels (22–30%). There was not such a difference between diabetic and normal coeliac arteries. Prostacyclin produced a concentration-related relaxation in the presence of indomethacin or indomethacin + PGF_2α. The relaxant potencies of PGI₂ were similar in the vessels from metabolically healthy and diabetic dogs. The IC₅₀ values for PGI₂ were 11·6 ± 1·3 and 11·8 ± 1·8 nmol l^-1 in normal and diabetic basilar arteries, respectively; they were 25·4 ± 3·2 and 26·2 ± 3·9 nmol l^-1 in control and alloxan-treated coeliac vessels. These results indicate that normal and diabetic vessels may have differential reactivity to cyclooxygenase inhibitors, this difference being dependent on the vascular region.     

Urinary excretion of bile alcohols in normal children and patients with α1-antitrypsin deficiency during development of liver disease

Abstract. Healthy infants and children were found to excrete bile alcohol glucuronides in urine. Following isolation and hydrolysis, the bile alcohols were estimated by capillary gas-liquid chromatography. The daily urinary excretion of the major compound, 27-nor-5 β -cholestane-3α,7α,12α,24ξ,25ξ-pentol (a C₂₆ bile alcohol), ranged from 0·1 to 1·1 μmol/24 h per m² body surface area for healthy infants and children. Two groups of patients with α₁-antitrypsin deficiency (phenotype PiZ) were also studied during infancy and childhood, and biochemical liver function tests and liver morphology were compared to the excretion of bile alcohols. The highest excretion of the C₂₆ bile alcohol in urine was found in patients with α₁-antitrypsin deficiency and juvenile cirrhosis (2·1–8·4 μmol 24 h^-1 m^-2) regardless of preceding neonatal cholestasis. Patients with α₁-antitrypsin deficiency, neonatal cholestasis and subsequent fibrosis or normal liver morphology excreted bile alcohols within the normal range. The C₂₆ bile alochol constituted an average of 36% of the total bile alcohols in forty-three urine samples. This percentage was about the same in the three groups studied. The findings suggest that determination of urinary bile alcohols may be a valuable non-invasive diagnostic tool for patients with or at risk of developing liver cirrhosis.     

Effects on renal tubular protein reabsorption of the infusion of free haemoglobin

Abstract. Hydroxy-ethyl-starch cryopreserved blood with a mean free haemoglobin content of 260 μmol/l (SD 57 μmol/l) was infused into five normal volunteers. The renal clearance of six proteins of differing molecular weight was measured together with an analysis of the qualitative changes in protein excretion during the infusion and over the following 48 h. Other aspects of renal tubular function were assessed by the measurement of urinary N -acetyl-β- D -glucosaminidase, phosphate and amino acids. Increased clearance of low molecular weight proteins and N -acetyl-β- D -glucosaminidase occurred during the 12 h following infusion. β₂ microglobulin clearance × 10³ creatinine clearance rose from a mean of 0·4 (SD 0·1) to a mean of 74·5 (SD 32·3) and N -acetyl-β- D -glucosaminidase from 54·2 units/mmol creatinine (SD 18·0) to 1525 units/mmol creatinine (SD 2318). Increased amounts of low molecular weight proteins were detected in the urine by crossed immunoelectrophoresis. Creatinine clearance remained unaltered. It is argued that these changes may be caused by the competitive inhibition of low molecular weight protein reabsorption in the renal tubule by filtered haemoglobin.