Beta2-microglobulin and cystatin C in type 2 diabetes: assessment of diabetic nephropathy.

BACKGROUND: Changes in glomerular filtration rate (GFR) provide a valuable indicator of the progression of diabetic nephropathy (DN). This study was designed to demonstrate the clinical values of serum cystatin C (Cys C) and beta2-microglobulin in the assessment of renal function in type 2 diabetics by comparing them with the GFR, estimated from the uptake phase of 99 m technetium dimetiltriamino pentaacetic acid renogram (GFR-DTPA) and creatinine clearances. MATERIALS AND METHODS: 68 type 2 diabetic patients with (urinary albumin excretions (UAE) 30 - 300 mg/24 h) (n = 39) and without (UAE < 30 mg/24 h) (n = 29) microalbuminuria and 32 controls were enrolled in the study. Serum Cys C, beta2-microglobulin, creatinine, urinary microalbumin levels, creatinine clearances and GFR-DTPA values were determined in all groups. Non-parametric ROC curves, using a cut-off GFR-DTPA of 60 mL/min/1.73 m (2), were obtained for these markers. RESULTS: Serum Cys C, beta2-microglobulin, glucose and HbA1c concentrations were significantly higher in the group with diabetes compared to controls. In the patients with microalbuminuria, serum Cys C and glucose concentrations increased significantly in comparison to patients with normoalbuminuria, while no differences were observed for beta2-microglobulin levels. Serum creatinine concentrations, GFR-DTPA values and creatinine clearances were not different between both diabetic groups and controls. Cys C was positively correlated with beta2-microglobulin and creatinine and negatively with GFR values; beta2-microglobulin was also positively correlated with serum creatinine in microalbuminurics. A significant inverse correlation was found between beta2-microglobulin and GFR values in both microalbuminurics and normoalbuminurics. CONCLUSIONS: Increased Cys C and beta2-microglobulin in diabetics may be early indicators of incipient DN. The diagnostic accuracies of Cys C and beta2-microglobulin are superior to that of serum creatinine in distinguishing between mild and moderately reduced GFR.     

Serum level of immunoreactive gastrin: influence of kidney function.

Serum gastrin levels have been studied in 70 patients with chronically reduced glomerular filtration rate (GFR) as estimated by 51Cr-EDTA clearance, creatinine, and beta2-microglobulin values. A strong dependence upon GFR was found, although the correlation between gastrin levels and GFR was not as high as that between beta2-microglobulin and GFR, indicating the existence of extrarenal factors regulating the levels of circulating gastrin. In a separate group of 31 patients on maintenance dialysis the mean gastrin level was 65.9 pmol/l--that is, a fourfold increase compared to healthy subjects. Three of the uraemic patients had pronounced rises in serum gastrin in the range 800-1800 pmol/l. Finally, the influence of acute alterations of kidney function on serum gastrin was studied in 11 patients undergoing renal transplantation. In addition to a GFR dependence the results indicate the existence of feedback mechanisms in gastrin homeostasis. Although the clinical importance of the increased gastrin levels in renal failure is unknown, hypergastrinaemia occurs with sufficient frequency to be involved in upper gastrointestinal complications of uraemic patients.     

Haptoglobin Prevents Renal Dysfunction Associated with Intravariceal Infusion of Ethanolamine Oleate

Endoscopic injection sclerotherapy (EIS) with ethanolamine oleate was performed in patients with esophageal varices either with (18 patients) or without (19 patients) pretreatment with haptoglobin. The serum levels of urea nitrogen, creatinine, and beta 2-microglobulin, the creatinine clearance, and the urinary levels of N-acetyl-beta-D-glucosaminidase and urinary beta 2-microglobulin were measured before and after EIS. Indices of the glomerular filtration rate (serum levels of urea nitrogen, creatinine, beta 2-microglobulin; creatinine clearance) showed no significant changes after EIS in either the haptoglobin-treated or untreated groups. However, the increase in the urinary parameters after EIS (which are indices of renal tubular function) was suppressed in the haptoglobin-treated group (p less than 0.005 for urinary beta 2-microglobulin). Our results indicated that the administration of haptoglobin has a prophylactic effect on renal tubular dysfunction associated with the use of ethanolamine oleate in EIS.     

Evaluation of kidney damage in patients with acute lymphoblastic leukemia in long-term follow-up: value of renal scan

In order to evaluate potential long-term kidney damage of childhood leukemia and risk factors affecting renal damage, we studied 116 children treated for acute lymphoblastic leukemia (ALL) using the St. Jude Total XI and XIII protocols in 1991-1998. The median follow-up period after the completion of treatment was 35 months. The following parameters were examined: urinalysis, urinary creatinine (Cr), calcium (Ca), phosphorus, beta2-microglobulin, glomerular filtration rate (GFR), tubular phosphorus reabsorption (TPR), and renal function tests. Radiological evaluation included renal ultrasonography (US), and renal scans with DMSA or MAG-3 were performed. Blood chemistry and renal US patients were normal in all patients except two. GFR, TPR, urinary Ca/Cr, beta2-microglobulin, and renal scan were abnormal in 19.0%, 16.4%, 13.8%, 6.0%, and 40.5% of patients, respectively. The abnormality rate in GFR was significantly higher in patients <2 years of age. TPR abnormality was found to be significantly higher in patients who did not have G-CSF. An abnormal renal scan was associated with Hb < 10 g/dL, kidney infiltration, or hypertension at presentation and also occurred patients who underwent methotrexate treatment with frequent intervals during the follow-up period. Patients should be followed-up after cessation of therapy with the conventional tests mentioned above. In case of any abnormality, further detailed tests should be performed; renal scan seems to be more predictive for renal damage.     

Increased urinary beta 2-microglobulin after cancer chemotherapy

The serum and urinary concentrations of beta 2-microglobulin (beta 2-m) and creatinine and the urinary concentration of albumin and IgG were measured in 14 patients with hematologic malignancies before and during chemotherapy. There was a transient increase in urinary beta 2-m in nine of the 14 patients during chemotherapy. All of the nine patients but only one of the other five patients had had recent multiple chemotherapy. The urinary beta 2-m increased in 24 courses of chemotherapy given to these nine patients and was already abnormal before 13 of these courses. The increase in urinary beta 2-m was not associated with an increase in serum beta 2-m or a significant increase in urinary albumin or IgG excretion. These results suggest that chemotherapy causes a marked transient tubular proteinuria, particularly in patients who have had previous chemotherapy.     

Urinary neutrophil gelatinase associated lipocalin (NGAL), a marker of tubular damage, is increased in patients with chronic heart failure

Renal impairment, as measured by reduced glomerular filtration rate (GFR) and increased urinary albumin excretion (UAE), is prevalent in patients with chronic heart failure (CHF) and is associated with reduced survival. The prevalence of structural tubular damage in CHF is unknown. We investigated 90 CHF patients and 20 age and sex matched healthy controls, and determined estimated GFR, UAE, N terminal-pro brain natriuretic peptide (NT-proBNP) and urinary neutrophil gelatinase associated lipocalin (NGAL) as a marker for tubular damage. CHF patients had significantly lower averaged estimated GFR (64+/-17 vs 90+/-12 mL/min/1.73 m(2), P<0.0001), but higher NT-proBNP and UAE levels (both P<0.0001). Median urinary NGAL levels were markedly increased in CHF patients compared to controls (175 (70-346) vs 37 (6-58) microg/gCr, P<0.0001). Both serum creatinine (r=0.26, P=0.006) and eGFR (r=-0.29, P=0.002) were significantly associated with urinary NGAL levels as were NT-proBNP and UAE but to a lesser extent. In conclusion, renal impairment in CHF patients is not only characterised by decreased eGFR and increased UAE, but also by the presence of tubular damage, as measured by increased urinary NGAL concentrations.     

糖尿病患者血、尿微球蛋白变化及血微球蛋白与肾小球滤过率的相关性研究

目的　观察糖尿病患者血、尿 β2 微球蛋白 (β2 MG)、尿α1 微球蛋白 (α1 MG)水平变化 ,探讨血 β2 MG与肾小球滤过率 (GFR)之间的相关关系。方法　采用放射免疫分析法及99Tcm—二乙三胺五醋酸 (99Tcm—DTPA)肾动态显像法对 44例糖尿病患者和 2 0名正常人进行血 β2 MG、尿 β2 MG、尿α1 MG及GFR检测及对照分析。结果　 (1)病程 <1年和 >10年糖尿病患者血 β2 MG与GFR有明显的负相关性 (P <0 .0 1) ;(2 )糖尿病患者血、尿 β2 MG及尿α1 MG水平均高于对照组 ,其尿α1 MG水平增高更明显 (P <0 .0 1) ;(3)病程 <1年的糖尿病患者其GFR值高于对照组 ,病程 >10年者其GFR低于对照组。结论　GFR与血 β2 MG具有一定相关性 ,尿α1 MG作为早期诊断糖尿病肾病的指标其灵敏性高于血、尿 β2 MG。     

酶联免疫吸附法测定尿中性肽链内切酶及其临床意义

目的:建立尿中性肽链内切酶(NEP)检测的酶联免疫吸附(ELISA)法,探讨该检测的临床意义。 方法:将研究组分为对照组(n=100) 、单纯肾小球疾病组(n=31)、急性肾小管损伤组(n=44)、慢性肾小管损伤组(n=48)、马兜铃酸肾病组(n=13)、慢性肾功能衰竭(CRF)组(n=13)。收集各组患者晨尿,用ELISA法测得尿NEP的浓度,并用相应尿肌酐值予以标化。同时检测各组患者的尿微量蛋白。 结果:急性肾小管损伤组尿NEP明显高于正常对照组(P=0.0001), 慢性肾小管损伤组、马兜铃酸肾病组、CRF组尿NEP均明显低于正常对照组(P均< 0.01),而单纯肾小球疾病组尿NEP与正常对照组无差异(P =0.3027)。急性组尿NEP与尿NAG呈正相关,与其他几种尿微量蛋白间无相关性。在其他几组内,尿NEP与肌酐清除率(Ccr)呈正相关,与尿微量蛋白呈负相关。在肾小球疾病组内尿NEP与尿微量蛋白无明显相关性。 结论:本研究首次建立了尿NEP检测的ELISA法,并用于临床研究。对尿NEP的检测,提供了一种快速、非损伤性测量手段,籍此帮助诊断近端肾小管损伤及判断病程。     

Comparative toxicity of gentamicin and cefotetan

In a prospective, randomized, comparative study, the renal, hepatic and gastrointestinal toxicity and effects on the vitamin K dependent coagulation factors of gentamicin and cefotetan were compared. Gentamicin, which in all but one patient was combined with a penicillin, was found to cause a significant decrease of glomerular filtration rate (GFR) after 1 week of treatment. In 6/14 patients a further decrease of GFR was found during the week following the last treatment day. The renal proximal tubular cells were affected by gentamicin, as evident from significant increases in urinary activity of 2 tubular enzymes, alanine aminopeptidase (AAP) and N-acetyl-beta-D-glucosaminidase (NAG), as well as rises of urinary beta 2-microglobulin. Changes in GFR and tubular function were reversible. No statistically significant changes of these variables were seen with cefotetan. One cefotetan treated patient developed diarrhoea of moderate severity and 2 patients in the same group developed minor increases of liver transaminases. A small but statistically significant decrease of the activity of the vitamin K dependent coagulation factors occurred during cefotetan treatment. No gastrointestinal or hepatic adverse reactions were observed in the gentamicin treated patients.     

N-acetyl-beta-glucosaminidase and beta 2-microglobulin. Their urinary excretion in patients with renal parenchymal disease

The urinary excretion of N-acetyl-beta-glucosaminidase (NAG) and beta 2-microglobulin (beta 2M) was studied in 43 patients with various forms of renal parenchymal disease. Patients with membranous nephropathy, membranoproliferative glomerulonephritis, focal segmental glomerulosclerosis, obstructive pyelonephritis, nephrosclerosis, and minimal change nephropathy generally had urinary NAG and beta 2M levels more than 3 SDs above those seen in normal subjects. Patients with progressive renal disease averaged higher NAG and beta 2M urinary levels than those with the same renal lesion and stable function. Since elevated urinary levels of NAG and beta 2M suggest renal tubular injury or dysfunction, our observations suggest tubulointerstitial involvement in a wide variety of renal diseases.     

Effect of add-on direct renin inhibitor aliskiren in patients with non-diabetes related chronic kidney disease

ABSTRACT: BACKGROUND: The renin-angiotensin-aldosterone system (RAAS) plays an important role in the progression of chronic kidney disease (CKD). Although dual RAAS inhibition results in worse renal outcomes than monotherapy in high risk type 2 diabetes patients, the effect of dual RAAS inhibition in patients with non-DM CKD is unclear. The aim of this study was to evaluate the potential renoprotective effect of add-on direct renin inhibitor in non-DM CKD patients. METHODS: We retrospectively enrolled 189 non-DM CKD patients who had been taking angiotensin II receptor blockers (ARBs) for more than six months. Patients were divided into an add-on aliskiren group and an ARB monotherapy group. The primary outcomes were a decline in glomerular filtration rate (GFR) and a reduction in urinary protein-to-creatinine ratio at six months. RESULTS: The baseline characteristics of the two groups were similar. Aliskiren 150 mg daily reduced the urinary protein-to-creatinine ratio by 26% (95% confidence interval, 15 to 37%; p < 0.001). The decline in GFR was smaller in the add-on aliskiren group ([MINUS SIGN]2.1 vs. -4.0 ml/min, p = 0.038). Add-on aliskiren had a neutral effect on serum potassium in the non-DM CKD patients. In subgroup analysis, the proteinuria-reducing effect of aliskiren was more prominent in patients with a GFR less than 60 ml/min, and in patients with a urinary protein-to-creatinine ratio greater than 1.8. The effect of aliskiren in retarding the decline in GFR was more prominent in patients with hypertensive nephropathy than in those with glomerulonephritis. CONCLUSION: Add-on direct renin inhibitor aliskiren (150 mg daily) safely reduced proteinuria and attenuated the decline in GFR in the non-DM CKD patients who were receiving ARBs.     

Urinary albumin and beta 2-microglobulin excretion rates in patients with systemic lupus erythematosus

The daily urinary albumin and beta 2-microglobulin excretion rates were measured with sensitive radioimmunoassays in 14 patients with systemic lupus erythematosus (SLE). The duration of SLE ranged from 0.5 to 18 years, mean 10 years. The mean age was 37 years. All patients except 5 received prednisone, 5-20 mg/day. None of the patients had proteinuria as judged by the "Albustix" test, and all had normal serum creatinine. The daily urinary albumin and beta 2-microglobulin excretion rates were nearly the same as those previously found by us in 27 adult control subjects with a mean age of 44 years. Our study shows that SLE patients without clinical proteinuria have a completely normal renal glomerular and tubular protein handling, irrespective of the duration of the disease.     

beta 2-Microglobulin levels in serum and urine of rheumatoid arthritis patients on gold therapy.

The levels of beta 2-microglobulin (beta 2-m) in serum and urine of 24 seropositive patients with rheumatoid arthritis (RA) treated with regular gold (sodium aurothiomalate) injections have been investigated. The values obtained were compared with levels from 20 seropositive patients with RA treated only with nonsteroidal anti-inflammatory drugs and 20 age and sex matched normal controls who had received no medication. A significant increase of urinary beta 2-m levels was found in the gold-treated RA group. No correlation between dose of gold received and the levels of beta 2-m in the urine could be established. There was also no correlation between the erythrocyte sedimentation rate (ESR) or total lymphocyte count and beta 2-m levels in serum or urine. We conclude that serum and urinary beta 2-m levels appear to be poor indices of joint inflammation, but sequential urinary beta 2-m levels may prove valuable in monitoring the development of renal tubular lesions due to gold therapy.     

The midnight-to-morning urinary cortisol increment method is not reliable for the assessment of hypothalamic-pituitary-adrenal insufficiency in patients with end-stage kidney disease

A previous study reported that the midnight-to-morning urinary cortisol increment method could be used to reliably assess the insufficiency of the hypothalamic-pituitary-adrenal (HPA) axis. The principal aim of the present study is to verify whether the midnight-to-morning urinary cortisol increment is a reliable method for the assessment of the HPA axis in patients with various degrees of impaired kidney function. Fifty-six clinically stable patients with chronic kidney disease (CKD) and 14 healthy subjects were enrolled in the present study. Patients with CKD were divided on the basis of glomerular filtration rate (GFR) into the following arbitrary groups: mild (GFR: 60-89 ml/min/1.73 m2, no.=15), moderate (GFR: 30-59 ml/min/1.73 m2, no.=12) and severe kidney insufficiency (GFR: 15-29 ml/min/1.73 m2, no.=13), and hemodialysis patients. Plasma cortisol and ACTH levels were measured. The HPA axis was assessed by short Synacthen test and overnight dexamethasone suppression test. Double voided urine samples were collected at midnight and waking in the patients and the controls. Urinary free cortisol (UFC) and creatinine levels were measured and the UFC/creatinine ratio (Cort/Cr) was calculated. Then, the Cort/Cr increment was calculated as the morning Cort/Cr minus the midnight Cort/Cr. Baseline plasma cortisol levels were not significantly different between two groups. However, we found that CKD patients had significantly greater plasma ACTH levels than controls. The patients with CKD had also significantly lower morning UFC levels than controls and there was a progressive fall in morning UFC levels with decreasing GFR. The assessment of the HPA axis in patients with GFR lower than 29 ml/min was hampered by falsely abnormal responses to the midnight-to-morning urinary cortisol increment method. Plasma cortisol responded normally to exogenously administered ACTH, while plasma cortisol was suppressed by overnight dexamethasone administration in all patients with CKD. In conclusion, this method is not a reliable test for assessment of the HPA insufficiency in patients with GFR lower than 29 ml/min.     

Tubular dysfunction in the deeply jaundiced patient with hepatorenal syndrome

We examined beta 2-microglobulin (B2MG) excretion, an index of tubular function, in patients with hepatorenal syndrome, in whom tubular function is generally regarded as normal. Urine B2MG was significantly higher in these patients than in control patients with normal serum creatinine concentration. Patients with high urine B2MG concentration had markedly higher serum bilirubin than did patients with normal values (31 +/- 3 vs. 10 +/- 8 mg%, p less than 0.001), whereas prothrombin activity, serum albumin and serum B2MG concentration were similar. A "threshold" serum bilirubin concentration of about 23 mg% differentiated patients with normal and high urine B2MG values. Renal morphology at autopsy was unremarkable in both groups. Tubular dysfunction, manifested by increased urinary excretion of B2MG, occurs in patients with hepatorenal syndrome and deep jaundice. This measurement cannot, therefore, be used to make a diagnosis of acute tubular injury, as due to aminoglycosides, in such patients.     

Liver transplantation in a 23-year-old tyrosinaemia patient: Effects on the renal tubular dysfunction

Orthotopic liver transplantation was performed on a 23-year-old female with hereditary tyrosinaemia. The disorder was diagnosed at 7 years of age due to severe rickets, and the patient was treated with a diet restricted in phenylalanine and tyrosine. Nineteen months before the transplantation she had an acute episode of diffuse gastrointestinal bleeding due to portal hypertension. Three subsequent bleeding episodes with accompanying ascites and signs of encephalopathy were considered life-threatening. Nine months after the liver transplantation the patient is well, but serum transaminases are slightly elevated. Without dietary restrictions serum tyrosine and inorganic phosphate are normalized, no succinylacetone can be detected in serum, and urinary excretion of p-hydroxyphenyllactate and p-hydroxyphenylpyruvate is normal. Excretion of amino acids, glucose and beta 2-microglobulin decreased significantly after the transplantation but is still elevated. The succinylacetone concentration in urine is about 20% of the preoperative level. After an oral tyrosine load, succinylacetone excretion increased sevenfold but no deterioration of the renal tubular function was observed and no tyrosine metabolites were detectable in serum. The findings indicate that the defective tyrosine metabolism occurs in the kidneys, but does not produce tubular dysfunction. The residual tubular dysfunction of the patient is probably due to irreversible damage of the tubular epithelium.     

Study of renal function by creatinine clearance

This paper was designed to investigate the correlation between the renal clearance and the plasma concentration of creatinine. Of the curve obtained, three segments were studied: 1 - When the glomerular filtration rate (GFR) was greater than 60 ml per min. the plasma concentration fluctuated between 0.44 and 1.59 mg/dl. 2 - When GFR was between 30 and 60 ml per min. the plasma concentration reached 2.4 mg/dl, and 3 - When GFR was less than 30 ml per min. the plasma level increased to values as high as 28 ml/min. The urinary concentration of creatinine can be divided into two broad groups depending on the GFR. The boundary of this division is around 60 ml per min. This suggests that when GFR is depressed there would exist a limitation of the tubular secretion of creatinine or urinary dilution problems. It is demonstrated that there is a poor correlation between creatinine clearance and its plasma concentration, and hence the repeated measurement of creatinine clearance becomes imperative in the follow-up of patients.     

Serum beta-2-microglobulin in disorders of myeloid proliferation

Serum beta-2-microglobulin (beta 2-m) was measured on 182 samples from 98 patients with diseases characterized by proliferation of predominantly non-lymphoid marrow elements. Raised levels were found in myeloproliferative disorders, chronic granulocytic leukaemia, acute myeloid leukaemia and in many patients with myelodysplastic syndromes. The most striking elevation was seen in acute and chronic myelomonocytic leukaemia. These raised serum levels are probably derived from increased cell turnover, and it is suggested that cells of monocyte-macrophage series are particularly high producers of beta 2-m.     

Glomerular filtration rate is increased in man by the infusion of both D,L-3-hydroxybutyric acid and sodium D,L-3-hydroxybutyrate

A high glomerular filtration rate (GFR) is often found early in insulin-dependent diabetes mellitus (IDDM). It has been suggested that high circulating glucose, glucagon, and GH levels could play a role in this increase in GFR. On the other hand, patients with IDDM in poor metabolic control also have high circulating ketone body levels. This study was undertaken to determine whether exogenous D,L-3-hydroxybutyric acid at two infusion rates (40 and 30 mumol kg-1 min-1) for 180 min altered renal plasma flow (RPF), GFR, and the excretion rate of total protein, beta 2-microglobulin, and albumin in 11 normal (N) subjects and 11 IDDM patients in whom euglycemia was achieved and maintained using the insulin-glucose clamp technique. RPF and GFR were measured by a priming-continuous infusion of [125I]hippurate and [51Cr]EDTA, respectively. The 40 mumol kg-1 min-1 D,L-3-hydroxybutyric acid infusion increased RPF and GFR in both N and IDDM subjects. Mean RPF increased from 588 +/- 78 (+/- SD) to 706 +/- 129 mL min-1 1.73 m-2 in N and from 671 +/- 101 to 781 +/- 99 in IDDM. GFR increased from 121 +/- 11 to 151 +/- 15 ml min-1 1.73 m-2 in N and from 136 +/- 11 to 191 +/- 16 in IDDM. The filtration fraction also was significantly higher in IDDM than in N during the D,L-3-hydroxybutyric acid infusion. The 30 mumol kg-1 min-1 D,L-3-hydroxybutyric acid infusion increased RPF and GFR to a somewhat lesser extent in both groups. D,L-3-hydroxybutyric acid infusions increased the tubular reabsorption rate of ketone bodies and sodium. The increase in tubular sodium reabsorption rate was correlated significantly to that in the tubular ketone body reabsorption rate. A significant decrease in urinary pH was found during the D,L-3-hydroxybutyric acid infusion. D,L-3-Hydroxybutyrate sodium salt (30 mumol kg-1 min-1) also was infused in 5 of the 11 diabetic patients. A similar increase in GFR and RPF occurred. Both total protein and beta 2-microglobulin, but not albumin, excretion rates increased during D,L-3-hydroxybutyric acid (40 mumol kg-1 min-1) infusion in N and IDDM subjects. D,L-3-Hydroxybutyric acid infusion did not change plasma glucagon, GH, or renin activity.(ABSTRACT TRUNCATED AT 400 WORDS)     

The acute effect of insulin on renal haemodynamics and protein excretion in diabetics

Summary The effect of IV injection of 7 to 8 I. U. of insulin on renal haemodynamics and on urinary excretion of beta-2-microglobulin and of albumin was examined in 5 juvenile diabetics. Plasma glucose decreased from a mean value of 250 mg/100 ml to 117 mg/100 ml during the first 85 min after insulin. None of the patients had symptoms of hypoglycaemia and plasma adrenaline did not increase. There was no change in arterial blood pressure after insulin whereas pulse rate increased from 66/min to a maximum of 75/min. Glomerular filtration rate (GFR) and renal plasma flow (RPF) were decreased by 9 per cent and 13 per cent, respectively, during the first 90 min after insulin (2p < 0.01). There was also a statistically significant decrease in urine flow and urine secretion of several electrolytes, while filtration fraction remained almost constant. IV insulin decreased urinary excretion of beta-2-microglobulin and increased albumin excretion (2 p < 0.05). The albumin excretion induced by insulin is most likely due to increased amounts of filtered albumin, the mechanism of which remains unexplained.