Urinary PC-1 and N-acetyl-beta-D-glucosaminidase activity in patients with type 2 diabetes treated with metformin, gliclazide or glibenclamide.

BACKGROUND: Insulin resistance is a key feature of type 2 diabetes mellitus. Plasma cell differentiation antigen (PC-1) is an inhibitor of insulin receptor tyrosine kinase, and has been implicated in the pathogenesis of insulin resistance. METHODS: Urinary excretion of PC-1 was determined in 45 newly detected, obese diabetic patients treated with metformin (16 patients), gliclazide (14 patients) or glibenclamide (15 patients). Urinary N-acetyl-beta-D-glucosaminidase (NAGA), a lysosomal enzyme, was determined as a marker of tubular damage in diabetes. RESULTS: Basal urinary PC-1 excretion in all three groups of diabetic patients was at the level of healthy controls. Treatment with oral hypoglycaemic drugs did not change significantly the group level or the number of patients in each group with increased PC-1 activity. Urinary excretion of NAGA in patients with type 2 diabetes was not statistically different from the control level. Metformin and gliclazide treatment did not change significantly the group levels of NAGA excretion. However, glibenclamide treatment produced an increased urinary NAGA excretion in the whole group, and in about twice as many patients as in the pre-treatment period.

The predictive value of 131I-hippurate clearance in the prognosis of acute renal failure.

The aim of this investigation was to study the validity of the radionuclide methods in the estimation of kidney function, for prognosis and follow-up of acute renal failure (ARF). In thirty-one ARF patients, the evaluation of glomerular filtration rate (GFR) by 99mTc-DTPA clearance and effective renal plasma flow (ERPF) by 131 I-ortoiodohippurate (131I-OIH) clearance was performed within 7 days and after 6 months from ARF onset. All patients were divided in three groups according to 131I-OIH clearance values obtained within 7 days: group 1, under 150 mL/min; group 2, 150-250 mL/min; and group 3, over 250 mL/min. Seven days clearance values of both radiopharmaceuticals were found to be very low, however, GFR was found more severely impaired than ERPF. Clearance values obtained after 6 months demonstrated no recovery of renal function in the first group, partial recovery in the second and almost complete recovery in the third group. Patients with the lowest 131I-OIH clearance values at the ARF onset had no recovery of renal function, while in the other two groups recovery corresponded to initial 131I-OIH clearance values. In patients with ARF both, 99mTc-DTPA and 131I-OIH clearances were shown suitable for the follow up of renal function, however, only 131I-OIH clearance had a strong predictive prognostic value for renal function recovery in ARF.

Radionuclide voiding pattern in children with unstable bladder.

BACKGROUND: The purpose of this study was to investigate bladder function parameters by means of quantitative radionuclide cystography (QRC) in anxious, irritable children with unstable bladder. METHODS: Quantitative radionuclide cystography was performed in 18 children aged between 8 and 12 years, without evidence of neurologic and nephrologic disorders. Findings were compared with those obtained in 10 healthy children aged between 7 and 10 years. The dynamics of the bladder emptying were studied after intravenous injection of 37 MBq/10 kg b.w. 99mTc-diethylenetriaminepentaacetic acid (DTPA) in the posterior views. Images of 90 frames every 2 sec. were stored in the 64 x 64 computer matrix during voiding. The patients voided into a container and the volumes were measured. RESULTS: The parameters evaluated were: functional bladder capacity (ml)--FBC, expected bladder capacity (ml)--EBC, percentage of EBC (%), voided urine volume (ml)--VV, residual urine (ml)--RU, voiding time (sec)--VT, average flow rate (ml/sec)--AFR and peak flow rate (ml/sec)--PFR. There was a statistically significant difference between controls and children with unstable bladder in the following parameters: FBC 288 +/- 33 vs. 244 +/- 27 ml (p < 0.001), % of EBC 99 +/- 6 vs. 82 +/- 6% (p < 0.0001), VV 265 +/- 37 vs. 202 +/- 35 ml (p < 0.0001), RU 22 +/- 11 vs. 48 +/- 19 ml (p < 0.007), AFR 13 +/- 5 ml/sec vs. 9 +/- 4 ml/sec. (p < 0.01) and PFR 19 +/- 2 vs. 13 +/- 3 ml/s (p < 0.0001), respectively. The VT obtained from the control group of 23 +/- 9 s did not differ significantly from the value of children with unstable bladder of 28 +/- 14 s. CONCLUSION: The results show that quantitative radionuclide cystography is a simple, noninvasive method, which allows a good separation of patients with unstable bladder from the children with normal voiding pattern.

[Functional and morphologic study of kidneys using radioisotope methods]. / Funkcijska i morfoloska ispitivanja bubrega radioizotopskim metodima.

This survey of investigation of renal function and morphology by radionuclides. Radiopharmaceuticals with different pathways of renal excretion or fixation, and methods of their use are presented. These methods assess separate kidney function, as well as blood and urine flow by a noninvasive way.

Cytokine levels in patients with urinary tract cancer.

It is known that cytokine exert cytotoxic effect on certain tumor cell lines, as well as that cytokines production might be influenced by tumor cells. Therefore, serum and urine levels of TNF and IL-1 were determined by RIA in 20 patients with upper urinary tract cancer, 26 with urinary bladder cancer, and compared with those of 52 healthy blood bank donors. Serum levels of TNF in cancer patients were found moderately increased, and those of IL-1 unchanged. Conversely, urinary excretion of TNF was shown decreased in both upper urinary tract and urinary bladder cancer patients, while IL-1 excretion was not significantly changed. Tumor grade was not found to influence serum and urine levels of the cytokines studied. Unstimulated and PHA- and Con A-stimulated production of TNF by peripheral blood mononuclear cells was within the normal range, suggesting that other sources such as tumor cells have to be considered for the increase in the serum level. Basal production of IL-1 was lowered in patients with upper urothelial cancer. Further investigation are required to ascertain and reveal the possible mechanism of the decreased urinary excretion associated with increased serum levels of TNF in urinary tract cancer.

[The role and significance of integrins as cell surface receptors]. / Uloga i znacaj integrina kao receptora.

Integrins are transmembrane glycoproteins occurring in cell membranes as hetorodimers made of two subunits, alpha and beta, associated with noncovalent bonds. Ligands of these receptors are several proteins from the interstitial tissue as well as adhesive proteins from the surface of neighbouring cells. Linking of the corresponding ligands to different integrins influence the adhesion but also the functional state of the cell with these integrins. The paper deals with basic properties of integrins as cell receptors, division into the main subgroups as well as a review of adhesive proteins, important for integrin function. The important role of integrin function in some pathologic states is emphasized.

[Use of angiotensin converting enzyme inhibitors in nephrology]. / Primena inhibitora enzima konverzije angiotensina u nefrologiji.

A survey of the use of angiotensin converting enzyme inhibitors in nephrology is presented. Angiotensin converting enzyme inhibitors were used in hypertensive glomerular disease, as well as with particular success in prevention and treatment of diabetic nephropathy. Malignant hypertension generally responds to angiotensin converting enzyme inhibitors. Guidelines for treatment of hypertension in chronic renal failure, and in end-stage-kidney disease patients on chronic dialysis or after kidney transplantation, with angiotensin converting enzyme inhibitors are reviewed.

[Mesangium: interactions between mesangial cells and extracellular matrix]. / Mezangijum: odnosi mezangijskih celija i ekstracelijskog matriksa.

This is a survey of the recent data on glomerular mesangium. Besides its structural role as the main part of the capillary network, mesangial cells play a certain role in the formation and degradation of the extracellular matrix, in the spread and processing of circulating macromolecules, and in the regulation of glomerular capillary flow and filtration through its contractile characteristics. Mesangial cells possess a variety of receptors for hormones and autacoids, and are equipped with ectoenzymes whose function may be the control of available autacoids and hormones at their receptor sites. Mesangial cells secrete several cytokines and growth factors, and are their target. Interactions between mesangial cells, soluble cytokines and extracellular matrix could promote cell proliferation and unregulated deposition of extracellular matrix resulting in progressive mesangial and glomerular sclerosis.

Myoglobin elimination in end stage kidney disease patients on renal replacement treatment.

Increased serum myoglobin levels were previously found in patients with chronic renal failure. In this report we have studied the effects of dialysis on myoglobin elimination in patients on CAPD, IPD, cuprophan and polyacrylonitrile (PAN) membrane hemodialysis. Peritoneal dialysis removed a significant amount of myoglobin, CAPD 480 +/- 65 micrograms/day, IPD 270 +/- 25 micrograms/12 h treatment, while with cuprophan dialysis none, and with PAN dialysis only an insignificant amount of myoglobin. The serum myoglobin levels were 250 +/- 18 and 264 +/- 14 micrograms/l on cuprophan and a 3 month dialysis on PAN membrane, respectively. Markedly increased serum levels were also found in CAPD and IPD patients on peritoneal dialysis, 227 +/- 25 and 286 +/- 32 micrograms/l respectively. This study has shown that there is an increased serum myoglobin concentration in end-stage kidney disease patients on dialysis. Although peritoneal membrane is permeable to myoglobin, a relatively small amount is removed, and the serum level in CAPD and IPD patients was not significantly different from the serum myoglobin concentration in hemodialysis patients. Furthermore myoglobin could not be removed by hemodialysis membrane and an analysis of its important extrarenal catabolism level points were analyzed.

[Fixation of tubules with radioactive technetium dimercaptosuccinate in parenchymal diseases of the kidney]. / Fiksacija u tubulima dimerkaptosukcinata oblezenog radioaktivnim tehnecijumom u parenhimskim oboljenjima bubrega.

In order to evaluate tubular function 99mTc-DMS dynamic kidney scintigraphy and 99mTc-DMS uptake determinations were performed in 55 patients with endemic nephropathy, diabetic nephropathy and glomerulo nephritis. From 64-656th segment of computerized radiorenograms 99mTc-DMS uptake and curve slope were assessed and compared with the corresponding parameters of 20 healthy subjects. Both parameters were decreased in patients of all three groups. Tubular uptake of 99mTc-DMS measured during 60 sec. 4 hours after 99mTc-DMS administration, was decreased in endemic nephropathy and diabetic nephropathy, but without a significant difference in glomerulonephritic patients. The study of the relationship between 4 hour 99mTc-DMS tubular fixation and glomerular filtration rate, estimated by 99mTc-DTPA clearance, showed a positive correlation only in patients with diabetic nephropathy. Patients with renal failure from all three groups had more seriously impaired tubular handling of 99mTc-DMS, that correlated with reduction of the glomerular filtration rate. The present data showed more severe impairment of tubular function in patients with endemic nephropathy and diabetic nephropathy than in glomerulonephritic patients. The method was suitable for estimation of the tubular function.

Beta 2-microglobulin elimination in end-stage renal disease patients on renal replacement therapy.

beta 2-microglobulin (beta 2M) is a small molecular mass protein associated with dialysis amyloidosis. We have studied beta 2M elimination in end-stage renal disease (ESRD) patients treated by peritoneal dialysis. In 12 patients on continuous ambulatory peritoneal dialysis (CAPD) and 7 patients on intermittent peritoneal dialysis (IPD) 30.4 +/- 4.2 mg/day and 21.3 +/- 1.8 mg/12 hour of beta 2M, respectively, were removed by dialysis fluid. Approximately the same amount of beta 2M was removed by each of four 2-L exchanges in CAPD; however, the most efficient removal of beta 2M was in the first IPD exchange. Serum beta 2M levels in these patients were 25.7 +/- 4.4 and 31.4 +/- 5.2 mg/L, respectively. In 24 patients on hemodialysis using cuprophan membrane the serum level of beta 2M was 55.1 +/- 4.1 mg/L. After a 3-month dialysis on polyacrylonitrile (PAN) membrane, the serum beta 2M level decreased to 45.0 +/- 2.3 mg/L. A substantial amount of beta 2M was removed by urine, 14.6 +/- 2.3 mg/L, and saliva, 2.3 +/- 0.4 mg/L. This study has shown markedly increased beta 2M levels in patients on conventional hemodialysis treatment, predisposing to beta 2M-related amyloidosis. A significant amount of beta 2M was removed during both CAPD and IPD treatment.

Thyroid hormone profiles in experimental acute renal failure.

Thyroid hormone profiles were determined in two groups of dogs made uremic, either by i.v. uranyl nitrate 10 mg/kg BW injection or by bilateral ureteral ligation, and in one group of sham-operated animals. Each group consisted of 6 dogs and served as its own control. From blood samples taken in 12-h intervals up to 144 h for uranyl nitrate-injected dogs and 96 h for operated dogs, serum levels of T4, T3, fT4, fT3, rT3, and cortisol were measured by radioimmunoassays. The results obtained in both groups of uremic dogs showed an initial sharp fall of T4, T3, fT4, and fT3 followed by a plateau or retarded decrease. In sham-operated dogs the fall of these hormones was slight and of short duration. Reverse T3 had a tendency to increase in all groups examined, but a significant elevation was recorded only after bilateral ureteral ligation. In this group cortisol serum levels were found the highest, being also significantly increased in the other two groups. The temporal coincidence of the most marked alterations in T3, rT3, and cortisol serum concentrations indicates a significant role of stress in thyroid dysfunction. Although serum creatinine rise and weight loss were not parallel with thyroid hormone alterations, the involvement of uremic compounds and malnutrition in this process is also quite clear. Thus, the data presented suggest simultaneous influences of uremic toxins, stress, and malnutrition on the induction of thyroid dysfunction in dogs made uremic by uranyl nitrate injection or bilateral ureteral ligation.(ABSTRACT TRUNCATED AT 250 WORDS)

[Diurnal changes in the levels of immunoreactive parathyroid hormone and calcitonin in patients with chronic renal insufficiency]. / Dnevne promene koncentracije imunoreaktivnog paratireoidnog hormona i kalcitonina bolesnika s hronicnom bubreznom insuficijencijom.

The circadian rhythms of the serum immunoreactive parathyroid hormone (iPTH) and calcitonin concentration were examined in 6 patients with chronic renal failure (CRF) not treated by haemodialysis. In 3 patients on haemodialysis the influence of haemodialysis with cuprophan and polyacrylonitrile membranes (in a.m. and p.m. periods of day) on serum concentration of these was investigated. The results demonstrate that in patients with CRF in predialysis period the circadian rhythm of serum iPTH concentration is at least partially preserved. However, the effect of dialysis on serum C-terminal iPTH concentration showed a sharp progressive fall of the concentration during haemodialysis on polyacrylonitrile membranes. The study of the circadian rhythm of serum calcitonin concentration in CRF patients with the six hours intervals between blood sampling could not reveal changes which favour the opinion of the existence of circadian rhythmicity. In patients on haemodialysis during haemodialysis with cuprophan membranes a rise of serum calcitonin concentration was observed.

[Atrial natriuretic peptide. Mechanisms of its action]. / Atrijumski natriureticki peptid. Mehanizmi delovanja.

A survey of the mechanisms of stimulation of secretion and of atrial natriuretic peptide (ANP) and its action is presented. Action of this hormone is particularly important on the kidney, the cardiovascular system and on some endocrine tissues. Major secretory organs are atrial myocytes, with an increased intra-atrial pressure as the stimulus. Under the action of ANP occurs dilatation of arterial blood vessels, often masked in vivo by a secondary increase in the sympathetic tone. ANP decreases the venous return with consecutive lowering of cardiac output. In a kidney an increase in diuresis and natriuresis occurs. Among the actions on the endocrine tissues inhibition of aldosterone secretion and, most probably, inhibition of renin secretion, are the most important.

[Cortisol and aldosterone plasma levels in patients with acute renal insufficiency]. / Nivoi kortizola i aldosterona u plazmi bolesnika sa akutnom bubreznom insuficijencijom.

The paper deals with the study of cortisol and aldosterone plasma levels in patients with acute and chronic renal insufficiency. Various degrees of supranormal cortisol levels were found in all 6 examined patients with acute renal insufficiency in oligonauric phase of the disease. A gradual decrease was observed in diuretic stade. However, during the recovery period they were within normal limits. In 3 of 4 patients in whom acute changes changed to chronic renal insufficiency increased cortisol levels were registered. In one patient the elevated cortisol level achieved the upper limit of normal values. In both groups of examined patients, but not in all of them, moderately increased aldosterone plasma levels were found. The obtained results speak in favour of an important role of stress factors in patients with acute renal insufficiency.

[The effect of thyroxine on renal function in experimental acute renal insufficiency]. / Dejstvo egzogenog tiroksina na funkciju bubrega u eksperimentalnoj akutnoj bubreznoj insuficijenciji.

The aim of the study was to investigate the influence of exogenous thyroxine upon the kidney function in the experimental renal failure induced by the uranyl acetate application. Acute renal failure was induced by uranyl acetate in 32 rats, divided into 4 groups, each consisted of 8 rats. The group of untreated animals and the group of animals treated with thyroxine only were used as controls. Then glomerular filtration rate was determined in all the rats taken in the experiment. The comparison was made between the control or the group with acute renal failure without the thyroxine treatment and the groups treated with a single application of thyroxine before, simultaneously and after the uranyl acetate injection. An improvement of the glomerural filtration rate and a decrease of the blood nitrogen retention were obtained in rats with acute renal failure pretreated with thyroxine. Necrotic alterations of the kidney cortex were less marked in this group than in the group without thyroxine treatment. The improvements of the kidney function and morphology in acute renal failure suggest the possibility of the protective effect of thyroxine.

[Serum myoglobin levels in patients with acute and chronic renal insufficiency]. / Ispitivanje nivoa mioglobina u serumu bolesnika sa akutnom i hronicnom bubreznom insuficijencijom.

The serum level of myoglobin was studied in 20 patients with acute renal failure, in 16 chronic renal failure patients and in 94 patients on maintenance haemodialysis. The serum myoglobin level was significantly increased in the oligoanuric phase of acute renal failure, rapidly decreased during diuretic phase and attained apparently normal values in the recovery phase. In patients with chronic renal failure the serum myoglobin level correlated with serum creatinine and creatinine clearance as a measure of the glomerular filtration rate, indicating a major role of kidney in the metabolism of this low-molecular weight protein. It was established that myoglobin could not be removed by dialysis membrane and analysis of the myoglobin level in endstage kidney disease patients on maintenance hemodialysis has shown an important extrarenal catabolism of this protein.