Kidney function and size in normal subjects before and during growth hormone administration for one week

Abstract. Kidney function and size were studied in seven normal male subjects before and after administration of highly purified human growth hormone for 1 week. Glomerular filtration rate, renal plasma flow (steady-state infusion technique with urinary collections using ¹²⁵I-iothalamate and ¹³¹I-hippuran) kidney size (ultrasonic scanning) and urinary excretion rates of albumin and β₂-microglobulin (radioimmunoas-says) were measured. Highly purified growth hormone was injected subcutaneously, 2 IU in the morning and 4 IU in the evening. Glomerular filtration rate increased from (mean ± SEM) 114 ± 5 to 125±4ml/min x 1.73 m² ( P <0.01) and renal plasma flow increased from 554 ±30 to 601 ±36 ml/min ×1.73 m²( P < 0.01). Kidney size and urinary excretion rates of albumin and β₂-microglobulin did not change significantly.
Our results show that raising plasma growth hormone into a range similar to that found in insulin-dependent diabetics enhances glomerular filtration rate and renal plasma flow, while kidney size remains unchanged. Increased renal plasma flow is the major determinant of growth hormone induced elevation in glomerular filtration rate. Growth hormone may thus contribute to the enhancement of glomerular filtration rate and renal plasma flow typically found in insulin-dependent diabetics.     

Renal excretion of proteins and enzymes in workers exposed to cadmium

The proteinuria rate and the relative clearances of beta 2-microglobulin, orosomucoid, albumin, transferrin and IgG were measured in forty-two workers exposed to cadmium and in seventy-seven control workers. A tubular type proteinuria with an increased excretion of beta 2-microglobulin and often also a glomerular type proteinuria with an increased excretion of orosomucoid, albumin, transferrin and IgG were observed mainly in workers exposed to cadmium for more than 25 years and whose cadmium concentration in blood exceeded 1 microgram Cd/100 ml and that in urine 10 microgram Cd/g creatinine. The glomerular dysfunction was also suggested by an increased plasma level of beta 2-microglobulin and creatinine. Both tubular and glomerular impairments occurred with the same prevalence and were not necessarily associated. The increased release of beta-galactosidase by the kidney suggested that cadmium can damage some epithelial cells.     

尿蛋白与血尿酸对运动性肾损害评价的互补性研究

目的探讨尿蛋白与血尿酸联合检测对评价运动性肾损害的互补意义。方法问卷调查某部经2周训练后的新战士167名,并同步检测尿常规、血尿酸和血肌酐。用双向无序分类资料关联性检验方法分析尿蛋白与血尿酸联合检测对评价运动性肾损害的互补性。结果经双向无序分类资料关联性检验,χ2=2.39,P0.05;尿蛋白阳性与血尿酸增高关系密切,程度的Pearson列联系数C=0.1188。结论运动性肾损害可能存在肾小管和肾小球两种不同病理机制损害方式,尿蛋白阳性与肾小球损害密切,而血尿酸增高与肾小管损害更为密切。联合检测尿蛋白与血尿酸对评价运动性肾损害具有一定的互补性,有利于早期发现运动性肾损害及评价运动训练强度,可以科学指导运动训练以及防止运动性急性肾功能衰竭的发生。     

Atrial natriuretic peptide increases albuminuria in type I diabetic patients: evidence for blockade of tubular protein reabsorption

BACKGROUND: It has been suggested that atrial natriuretic peptide (ANP) contributes to the glomerular hyperfiltration of diabetes mellitus. Infusion of ANP increases the urinary excretion of albumin in patients with type I diabetes mellitus (IDDM). Although the increased albuminuria is attributed to a rise in glomerular pressure, alterations in tubular protein handling might be involved. PATIENTS AND METHODS: We have studied the effects of ANP in nine microalbuminuric IDDM patients. After obtaining baseline parameters, ANP was infused over a 1-h period (bolus 0.05 microgram kg-1, infusion rate 0.01 microgram kg-1 min-1). Renal haemodynamics, sodium and water clearance and tubular protein handling were studied. RESULTS: The glomerular filtration rate (GFR) increased from 116.4 +/- 8.9 to 128.3 +/- 8.8 mL min-1 1.73 m-2, whereas the effective renal plasma flow (ERPF) decreased from 534.3 +/- 44.3 to 484.9 +/- 33.3 mL min-1 1.73 m-2 (P < 0.05). As a result, the filtration fraction was significantly higher during infusion of ANP. ANP attenuated proximal tubular sodium reabsorption. Urinary albumin excretion rose from 87.57 +/- 21.03 to 291.40 +/- 67.86 micrograms min-1 (P < 0.01). Changes in the urinary excretion of beta 2-microglobulin and free kappa light chains were more marked, the excretion of beta 2-microglobulin increasing from 0.28 +/- 0.21 to 51.87 +/- 10.51 micrograms min-1 (P < 0.01), and of free kappa-light chains from 4.73 +/- 1.74 to 46.14 +/- 6.19 micrograms min-1 (P < 0.01). CONCLUSIONS: The observed rise in albuminuria during infusion of ANP does not simply reflect a change in glomerular pressure, but might at least partly result from an attenuation of tubular protein reabsorption.     

Behaviour of urinary excretion of lysozyme in renal diseases and in urinary tract infections (author's transl)]

Urinary excretion of lysozyme was investigated in a group of 66 patients with various renal diseases, nephrolitiasis and urinary tract infections. The results obtained demonstrate that the amount of the enzyme excreted is related to the entity of tubular damage whereas is not with glomerular damage. No correlation was found between lysozyme excretion neither to the degree of proteinuria neither to the amount of leukocytes and bacteria in the urine. In patients with urinary infections urinary lysozyme increases only when there is a tubular injury of some entity. In 90 pediatric patients with urinary infection and pyelonephritis lysozyme in the urine was found only in two cases. Therefore urinary lysozyme determination cannot be considered for the detection of early tubular injury and is not a helpful diagnostic tool in urinary tract infections.     

Dose-response study of atrial natriuretic peptide bolus injection in healthy man

Abstract. The effects of human atrial natriuretic peptide (ANP) on glomerular filtration rate (GFR), renal plasma flow (RPF), urinary flow rate, urinary sodium excretion, tubular function estimated by lithium clearance, and plasma levels of sodium and water homeostatic hormones were studied in a dose-response study with 50 healthy subjects. Placebo or ANP 0.5, 1.0, 1.5, or 2.0 μg kg^-1bwt was given as an intravenous bolus injection to five different groups. GFR rose after ANP, whereas no immediate change in RPF was observed. Significant increases with no distinct additional effect of ANP doses higher than 1.0 μg kg^-1were detected in filtration fraction, urinary flow rate and urinary excretion rate of sodium. Both proximal and distal fractional reabsorption of sodium was reduced and the effect seemed to flatten out at doses higher than 1 0 μ g kg ^-1. Dose-dependent increases in cyclic guano-sine monophosphate in urine and plasma were found after ANP bolus injection, and the rise in both was correlated with the increase in urinary sodium excretion. ANP caused a dose-dependent decrease in blood pressure and an increase in pulse rate. Plasma concentrations of angiotensin II and arginine vasopressin did not change after ANP.
In summary, we found that ANP bolus injection caused a natriuresis and diuresis in healthy man with a threshold at a dose of 1.0 μg kg^-1. No distinct further renal effects were observed with higher doses despite dose-dependent increases in urinary cGMP excretion and plasma cGMP. Inhibition of both proximal and distal tubular fractional sodium reabsorption by ANP contributed to the natriuretic effect. The correlation between the rise in cGMP and the increase in urinary sodium excretion is concordant with cGMP being a secondary messenger for ANP in man.     

93例肾脏疾病患者SDS-AGE非浓缩尿蛋白电泳分析

目的观察十二烷基硫酸钠-琼脂糖凝胶(SDS-AGE)非浓缩尿蛋白电泳在肾脏疾病诊断中的价值。方法采用SDS-AGE非浓缩尿蛋白电泳技术对93例肾脏疾病患者的蛋白尿进行分析。结果 93例肾病患者尿蛋白电泳中,肾小球性蛋白尿50例,肾小管性蛋白尿6例,混合型蛋白尿9例,白蛋白尿24例。结论 SDS-AGE非浓缩尿蛋白电泳的检测对明确肾病患者尿蛋白的性质、来源及各种蛋白的含量,判断肾脏损伤类型及程度具有较高的临床应用价值,且取材简便,敏感性高。     

Assessment of renal function: selected developments

Tests commonly used to assess the glomerular filtration rate (GFR) and to detect renal tubular damage are critically reviewed. Creatinine clearance which is frequently used for assessment of the GFR is prone to several errors. The plasma creatinine can be used to provide a rough guide but for reliable measurement of the GFR, 51Cr-EDTA clearance is recommended. Measurements of the urinary excretion of low molecular weight proteins, enzymes and kidney tissue proteins have been used to detect tubular damage. Of the low molecular weight proteins excreted, beta-2-microglobulin is unstable and measurement of retinol-binding protein or alpha-1-microglobulin is recommended for the detection of chronic renal tubular malfunction. Of the many enzymes that have been studied, urinary N-acetyl-beta-D-glucosaminidase or alanine aminopeptidase are recommended as being the most useful for the early detection of acute renal tubular damage. Among renal tissue proteins that have been measured in urine adenosine-deaminase-binding protein, a tubular brush border antigen appears to have considerable potential for providing early warning of renal allograft rejection.     

Serum and urinary proteins, lysozyme (muramidase), and renal dysfunction in mono- and myelomonocytic leukemia

Serum levels, urinary excretion, and clearances of several proteins of different molecular weights were studied in 18 patients with mono- and myelomonocytic leukemia. Nine patients had normal renal function (group A) and nine had impaired renal function with azotemia (group B). The majority of patients in both groups had increased concentration of immunoglobulins, particularly IgG, IgA, and IgM; IgD level was normal. Serum transferrin and alpha(2)-macroglobulin were frequently reduced while the level of ceruloplasmin was often increased, especially in patients with azotemia. The activity of lysozyme in the serum was high in all patients, but was considerably higher in group B.Proteinuria was found in most patients but was more prominent in group B. Almost invariably albumin constituted less than 25% of the total protein excreted. Qualitative analysis of various urinary proteins by immunochemical techniques and clearance studies suggested the presence of glomerular as well as tubular dysfunction. Determination of urinary lysozyme frequently showed no direct correlation between the serum level of the enzyme and its concentration in the urine or its clearance by the kidney. In addition to glomerular filtration, impaired tubular reabsorption may account for the high level of lysozyme in the urine. It is postulated that the very high level of lysozyme in the glomerular filtrate and possibly hypergammaglobulinemia may play a role in the induction of tubular damage. Renal impairment has been correlated with histological changes in the kidneys. From a comparative study of various leukemias, it seems that the combined glomerular-tubular dysfunction is a manifestation unique to mono- and myelomonocytic leukemia.     

Use of Paricalcitol as Adjunctive Therapy to Renin-Angiotensin-Aldosterone System Inhibition for Diabetic Nephropathy: A Systematic Review of the Literature

PurposeDiabetic nephropathy (DN) is a major complication of diabetes. Paricalcitol is a vitamin D analog that is typically used for secondary hyperparathyroidism in patients with chronic kidney disease but may have some beneficial effect on DN. This review evaluates the effect of paricalcitol in combination with renin-angiotensin-aldosterone system inhibitor therapy in managing DN.MethodsA literature search was conducted of PubMed and ClinicalTrials.gov. Limits were set to include only clinical trials in humans written in English. The search terms used were paricalcitol and diabetic nephropathy. The following outcomes of kidney function and damage as well as adverse drug events were assessed and included: 24-h urine albumin excretion, serum phosphorus and calcium concentrations, urinary albumin excretion rates, estimated glomerular filtration rate, and markers of inflammation and endothelial function.FindingsFour studies with a total of 389 patients were identified for review through the process described above. Two of the 6 studies provide evidence of the effect of paricalcitol on DN by way of reduction in urine albumin to creatinine ratio and urinary albumin excretion rate when compared with placebo. One study reported an increase in serum phosphorous, 1 study observed a decrease in estimated glomerular filtration rate, and 1 study reported no effect on inflammatory markers or endothelial function.ImplicationsThe number of clinical trials examining the effect of paricalcitol in DN is small. The studies that have been completed enrolled <300 patients. Paricalcitol can reduce protein in the urine, but there is no compelling evidence that it preserves kidney function.     

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.     

Compensatory Adaptation of Bicarbonate Excretion Following Acute Contralateral Kidney Exclusion in the Dog

Changes in the excretion of bicarbonate, sodium and potassium in one kidney after exclusion (complete sudden ligation of renal pedicle) of its partner have been studied in 16 dogs undergoing bicarbonate diuresis. Fluid balance, haematocrit, plasma electrolyte and protein concentrations were maintained constant throughout the experiment. Acute contralateral renal pedicle ligation lead to an immediate increase in bicarbonate as well as water, sodium and potassium excretion by the remaining kidney. The rapid and immediate increase in the fractional and absolute rates of bicarbonate excretion was observed at varying levels of bicarbonate loading, with the greatest response occurring at the highest infusion rate. Sodium, potassium and water excretion also increased in parallel with urinary bicarbonate loss. The increase in bicarbonate excretion was not accounted for by changes in extracellular fluid volume, plasma composition, glomerular filtration rate, effective renal plasma flow, aldosterone and vasopressin. In 8 sham-operated animals, no abrupt increase in sodium and bicarbonate excretion occurred despite similar continued infusion of sodium bicarbonate. It was concluded that exclusion of one kidney induces immediate adaptive excretory changes for sodium and bicarbonate in the remaining kidney, and that these changes are not accounted for by any of the known factors normally regulating sodium and bicarbonate excretion.     

A Micropuncture Study of Potassium Excretion by the Remnant Kidney

In order to study the mechanism of enhanced potassium excretion by the remaining nephrons of the remnant kidney, micropuncture and clearance experiments were carried out in rats after surgical ablation of 3/4 of the total renal mass. The potassium intake in all animals was approximately 5 meq/day. Animals were studied 24 h and 10-14 days after 3/4 nephrectomy. Balance measurements in the chronic animals before micropuncture study indicated that 24 h K(+) excretion by the remnant kidney was equal to that of the two kidneys before ablation of renal mass. Measurements of distal tubular inulin and potassium concentrations revealed progressive reabsorption of potassium in this segment of the nephron in both the 24-h and chronic 3/4-nephrectomized rats, as well as in normal control rats. A large increase in tubular fluid potassium content occurred between the end of the distal tubule and the final urine in the 3/4-nephrectomized rats, but not in the normal controls. These observations suggest that the segment of the nephron responsible for enhanced potassium excretion by remaining nephrons was the collecting duct.In additional experiments, potassium was completely eliminated from the diet of chronic 3/4-nephrectomized rats before micropuncture study. In these animals, no addition of K(+) occurred beyond the distal tubules. Normal rats infused with 0.15 M KCl to acutely elevate serum K(+) concentration, demonstrated reabsorption of K(+) in the distal tubule and a large addition of K(+) to the urine beyond the distal tubule.We conclude that the collecting duct is the major site of regulation of urinary potassium excretion in normal rats and is responsible for the adaptation to nephron loss by the remnant kidney.     

Renal toxicity of cadmium-metallothionein and enzymuria in rats

The mechanism of cadmium metallothionein (Cd-MT)-induced renal toxicity was studied in rats using urinary enzyme excretion as a marker for cellular damage. Animals were injected with either saline or Zn (20 mg of Zn as ZnSO4/kg b.wt.) at 0.5, 4 or 24 hr before injection of Cd-MT (0.3 mg of Cd as Cd-MT/kg b.wt. i.p.). Activities of two brush border enzymes, alkaline phosphatase (ALP) and gamma-glutamyl-transpeptidase (GGT), and a lysosomal enzyme, N-acetyl-beta-D-glucosaminidase (NAG), were measured in 24-hr urine collections. Urinary excretion of all three enzymes was increased significantly after Cd-MT injection. Both ALP and GGT excretions reached a maximum at 24 hr whereas NAG excretion reached peak values at 48 hr after Cd-MT injection. The excretion of all three enzymes decreased to the control level by the 3rd day. Zn pretreatment alone had no effect on urinary enzyme excretion. Pretreatment with Zn salts at 0.5 and 2 hr before Cd-MT injection did not show any difference in the urinary excretion of the enzymes as compared with the saline-treated controls. However, injection of Zn salts at 24 hr before Cd-MT injection resulted in a significant decrease in the excretion of the lysosomal enzyme NAG whereas both ALP and GGT excretions were unchanged. Extensive proximal tubular damage was observed morphologically in all the rats injected with Cd-MT, but the cellular damage was less in rats pretreated with Zn sulfate 24 hr before Cd-MT injection.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of antipyrine and phenobarbital on renal gamma-glutamyltransferase excretion in human urine

Serum gamma-glutamyltransferase is used as a marker of hepatic enzyme induction. The kidney contains high activities of gamma-glutamyltransferase in the brush border membrane of the proximal tubule, from which it is released into urine. This study investigated the effect of phenobarbital and antipyrine, two inducers of hepatic monoxygenases and gamma-glutamyltransferase, on the urinary excretion of renal gamma-glutamyltransferase. Three groups (n = 6) of healthy male volunteers received 100 mg phenobarbital for 7 and 14 days and 1200 mg antipyrine for 7 days, respectively. Antipyrine and phenobarbital increased antipyrine elimination, serum gamma-glutamyltransferase, and the urinary excretion of renal gamma-glutamyltransferase, whereas urinary beta-N-acetylglucosaminidase, beta-glucuronidase, and total protein and glucose excretion were unchanged. No correlation was found between serum and urinary gamma-glutamyltransferase or both enzymes and antipyrine elimination. Increases in antipyrine elimination were positively correlated to increases in serum, but not urinary gamma-glutamyltransferase. The findings suggest that antipyrine and phenobarbital increase urinary gamma-glutamyltransferase excretion. However, the increase in urinary gamma-glutamyltransferase does not reflect the magnitude of hepatic enzyme induction.     

Human neutral brush border endopeptidase EC 3.4.24.11 in urine, its isolation, characterisation and activity in renal diseases

Human neutral brush border endopeptidase (NEP) was purified from the urine of patients suffering from acute toxic tubulointerstitial nephropathy. An enzyme preparation with specific activity of 102 Ug(-1) protein was obtained. The urinary activities of neutral endopeptidase and alanine aminopeptidase were measured in patients with renal disease and in 30 control patients, resulting in a reference range from 0.1 to 0.7 Ug(-1) creatinine and 1.4-14.1 Ug(-1) creatinine, respectively. Urine enzyme activities were highest in patients with acute tubulotoxic renal diseases. Neutral endopeptidase and alanine aminopeptidase activities were found to be 6.5- and 10-fold higher than the upper value of the reference range, respectively. Smaller increases in the rate of excretion of these enzymes (2.5- and 3.5-fold), respectively, were observed in patients suffering from acute tubular insufficiency and even lower increases, 2- and 1.5-fold, respectively, were observed in patients with chronic renal diseases. In diabetics and kidney transplant patients the enzyme excretion rates were within the reference range. Assay of both transmembrane metalloproteinases in urine may prove valuable in serving as markers for renal toxicity. Together with beta-NAG these enzymes could be employed as differentiation markers between acute and chronic tubular insufficiency.     

Biomarkers of acute renal injury and renal failure

Acute renal failure (ARF) is a frequent problem in the intensive care unit and is associated with a high mortality. Early recognition could help clinical management, but current indices lack sufficient predictive value for ARF. Therefore, there might be a need for biomarkers in detecting renal tubular injury and/or dysfunction at an early stage before a decline in glomerular filtration rate is noted by an increased serum creatinine. A MEDLINE/PubMed search was performed, including all articles about biomarkers for ARF. All publication types, human and animal studies, or subsets were searched in English language. An extraction of relevant articles was made for the purpose of this narrative review. These biomarkers include tubular enzymes (alpha- and pi-glutathione S-transferase, N-acetyl-glucosaminidase, alkaline phosphatase, gamma-glutamyl transpeptidase, Ala-(Leu-Gly)-aminopeptidase, and fructose-1,6-biphosphatase), low-molecular weight urinary proteins (alpha1- and beta2-microglobulin, retinol-binding protein, adenosine deaminase-binding protein, and cystatin C), Na+/H+ exchanger, neutrophil gelatinase-associated lipocalin, cysteine-rich protein 61, kidney injury molecule 1, urinary interleukins/adhesion molecules, and markers of glomerular filtration such as proatrial natriuretic peptide (1-98) and cystatin C. These biomarkers, detected in urine or serum shortly after tubular injury, have been suggested to contribute to prediction of ARF and need for renal replacement therapy. However, excretion of these biomarkers may also increase after reversible and mild dysfunction and may not necessarily be associated with persistent or irreversible damage. Large prospective studies in human are needed to demonstrate an improved outcome of biomarker-driven management of the patient at risk for ARF.     

Immunological and ultrastructural analysis of loss of tubular membrane-bound enzymes in patients with renal damage

The pathophysiological background of shedding of membrane-bound enzymes from the proximal tubule was assessed in urine specimens of patients with renal damage applying immunospecific affinity-chromatography, immunotitration, ultracentrifugation, electroimmunodiffusion, immunohistology, as well as negative staining technique. Compared to healthy controls, patients with kidney injury, e.g. after administration of potentially nephrotoxic drugs (cytostatics, contrast media) revealed an increased excretion rate of vacuolar membrane fragments (50-500 nm) into urine. The brush border (BB) of the proximal tubule was identified as a main source of urinary blebs as concluded from immunoelectrophoretic and immunohistochemical analysis. In addition, the marker enzyme profile of urinary vacuolar blebs was similar to that of the BB membrane from human kidney. The results further evidenced that, during the initial phase of tubular injury, 5-10 nm surface glycoproteins of the BB, among them Ala-Leu-aminopeptidase and portions of gamma-glu-transpeptidase, are released into urine; this might be followed by increased blebbing of macromolecular BB fragments, indicating more severe membrane disruption.     

Urinary excretion of epidermal growth factor in living human kidney donors and their recipients

Abstract. Epidermal growth factor (EGF) is a growth-promoting peptide that is synthesized in the distal tubules of the kidney and excreted in urine. EGF has been suggested to play a role in the repair after renal tissue damage, as well as in compensatory growth of the remaining kidney after uninephrectomy. The present study examined the urinary EGF excretion after uninephrectomy and transplantation among relatives. The urinary EGF excretion rate and the glomerular filtration rate (GFR) were followed for 26–54 days in 16 healthy kidney donors and nine recipients. After uninephrectomy the median urinary EGF excretion rate in the donors was not 50% of the pre-operative value, but around 65% (95% confidence limits of the median on the fifth post-operative day: 59–72%). This suggests that there is a compensatory increase in the EGF excretion rate from the remaining kidney of around 30% after uninephrectomy. A similar compensatory increase was demonstrated for GFR, indicating that the compensatory changes in EGF excretion rate and GFR might be correlated. In the transplanted kidneys, GFR was consistently around 15% lower and EGF excretion rate around 40% lower than in the corresponding kidneys remaining in the donors. This might reflect ischaemic and drug-induced damage of the transplanted kidneys. The present study demonstrated a compensatory increase of around 30% in urinary EGF excretion from the remaining kidney after uninephrectomy in healthy humans. Whether EGF plays a role in the adaptive processes in the remaining kidney or whether changes in EGF excretion are merely of a secondary nature is still uncertain.     

Low concentrations of intravenous polygelines promote low-molecular weight proteinuria

BACKGROUND: Previously we observed that atrial natriuretic peptide (ANP)-induced albuminuria was accompanied by an increase in urinary excretion of the low-molecular weight protein (LMW protein) beta2-microglobulin (beta2-m), suggesting that the albuminuria may at least partly be the result of blockade of tubular protein reabsorption. However, in our experiments ANP was dissolved in the polygeline Haemaccel (Hoechst, Behring-Werke, Marburg Germany) to prevent adhesion of ANP to the infusion system. Anecdotal reports have shown that high dosages of polygelines such as Haemaccel or Gelofusine (Braun NPBI Oss, the Netherlands) may influence tubular protein handling. In the present study we have evaluated the effect of a low and high doses of the polygeline Haemaccel on proteinuria. In addition, we have reassessed the effects of ANP. MATERIALS AND METHODS: We measured urinary beta2-microglobulin (beta2-m) and albumin excretion in healthy volunteers after infusion of a high-dose pure Haemaccel (0.04 mL kg(-1) min(-1) for 60 min), a low-dose Haemaccel (0.01 mL kg(-1) min(-1) for 60 min followed by infusion of 0.02 mL kg(-1) min(-1) for 60 min) and a low-dose Gelofusine (dose comparable to the low-dose Haemaccel). In addition we performed similar studies using ANP dissolved in saline and Haemaccel. RESULTS: Infusion of Haemaccel caused a dose-dependent increase in urinary excretion of beta2-m. There were no differences between Haemaccel and Gelofusine. After infusion of ANP dissolved in Haemaccel urinary beta2-m excretion increased from 0.05 +/- 0.03 microg min(-1) to 27 +/- 10 microg min(-1) and urinary albumin excretion increased from 4.5 +/- 1.1 microg min(-1) to 9.7 +/- 6.3 microg min(-1) (P<0.05). During ANP + saline infusion, urinary beta2-m excretion did not change, whereas the urinary albumin excretion increased from 5.3 +/- 1.5 microg min(-1) to 7.9 +/- 2.4 microg min(-1) (P<0.05). CONCLUSIONS: Our study demonstrates that even low doses of the polygelines Haemaccel and Gelofusine profoundly attenuate the tubular reabsorption of the low-molecular weight protein beta2-m. Atrial natriuretic peptide does not affect tubular protein reabsorption. Therefore, the rise in albuminuria during ANP infusion most likely reflects alterations in glomerular permeability.