SVIBOR - Project code: 3-01-203

MINISTRY OF SCIENCE AND TECHNOLOGY

Strossmayerov trg 4, HR - 10000 ZAGREB
tel.: +385 1 459 44 44, fax: +385 1 459 44 69
E-mail: ured@znanost.hr

SVIBOR

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Project code: 3-01-203


PATOPHYSIOLOGY AND TREATMENT OF URAEMIA


Main researcher: MILUTINOVIĆ, SLOBODAN (44001)


Assistants
Type of research: applied
Duration from: 07/15/91. to 12/31/95.
Papers on project (total): 167
Papers on project quoted in Current Contents: 14
Institution name: Bolnica "Sveti duh", Zagreb (129)
Department/Institute: Department of Nephrology and dialysis Internal Clinics Sveti Duh Hospital
Address: Ulica Sveti Duh 64,
City: 10000 - Zagreb, Croatia
Communication
Phone: 385 (0)41-579-252
Phone: 385 (0)41-171-111 / 290,258,387
Fax: 385 (0)41-570-240
Summary: We performed clinical and in vitro investigations on the role of hormonal, biochemical and toxicological alterations in developpment of complications in chronic uremic patient including parathyroid glands, bone and connective tissue, peripheral nerves,cell-mediated immunity and peripheral insulin receptors. The most significant scientific contributions are the following: several guanidino substances from uremic plasma inhibit insulin receptor binding contributing to uremic glucose intolerance; the risk of diabetic uremic patients (pts) to developp aluminum intoxication is increased compared to nondiabetic uremics due to an increased aluminum absorption from the gut; inflammation of parathyroid glands could bring about a remission of secondary hyperparathyroidism; pulse therapy with calcitriol can controll secondary hyperparathyroidism; long-term dialysis markedly increases the risk of carpal tunnel syndrome,dialysis amyloidosis and peripheral neuropathy; the most sensitive and specific electrophysiologic parameter of uremic neuropathy is the amplitude of F-wave and H-wave, rather than motor conduction velocity; the prevalence of hypertension in erythropoietin-treated uremic pts is markedly increased in spite of use of small doses to avoid a rapid increase in hematocrit;calcium blocker amlodipin is markedly more efficient than ACE inhibitor enalapril in controlling hypertension i volume and sodium overloaded uremic patients. The prevalence of hepatitis C in dialysed pts is increasing. Uremia, and dialysis as well, inhibits monocyte phagocytosis, the number and activity of natural killer cells what could be associated with increased prevalence of infection ; secretion of tumor necrosis factor and interleukin-1 by macrophages is increased what could be associated with chronic inflammatory response in uremia and amyloidosis. The presence of P-fimbriae on Esch coli markedly increases the bacteriological failure rate after antibiotics therapy. Monotherapy of uremic pts with severe bacterial infection is efficient with new cefalosporin cefpiramide as well as with ceftazidime.Farmacokinetics of ceftriaxone is markedly changed in uremia; there is a small subpopulation of patients who can not compensate the reduced renal elimination by increased hepatic clearance and in these patients a marked plasma cummulation of the drug takes place. Taken altogether, the results increase our understanding of the role of specific patophysiological factors in developpment of chronic complications of uremic patients.

Keywords: Uremia, hemodialysis, hyperparthyroidism, insulin receptors,dialysis amyloidosis,carpal tunnel syndrom,TNF, Interleukin-1,Natural killer cells, hypertension, erythropoietin, guanidino-substances, oxalosis, ticlopidin, cefpiramide, P-fimbriae, uremic neuropathy

Research goals: The aim is to investigate the prevalence, transmission pathways and clinical picture of hepatitis C in 140 regularly dialysed pts. To proceed with investigation of cell immunity of monocytes connected with higher infections rate of uremic pts; to investigate secretion of tumor necrosis factor and Interleukin-1 in connection with enhanced catabolic rate of uremic pts, and with increased beta-2-microglobulin and dialysis amyloidosis. To find out the prevalence of dialysis amyloidosis related to aluminum cummulation and secondary hyperparathyroidism.To find out the most sensitive and specific electroneurologic parameter to detect and follow-up uremic neuropathy. To investigate pharmacokinetics, efficacy and safety of drugs especially in relation to interindividual variability, influence of uremia-related changes in hepatic drug metabolism and of residual renal clearance. To investigate the pharmacotherapeutic intervention to increase the efficacy of dialysis. To evaluate the efficacy of cefpiramide monotherapy in uremic pts with severe bacterial infections. To evaluate the functional and morphological alteration of myocard in uremia,with respect to potentially reversible cardiovascular risk factors in uremia. Altogether the aim is to improve evaluation of the quality of life of dialysed uremic, by establishing relevant set of parameters to follow up the adequacy of medical interventions in dialysis.

COOPERATION - PROJECTS


  1. Name of project: 3-01-038 Biomehanika muskulo-skeletnog sustava u različitim uvjetima
    Name of institution: Zavod za anatomiju Medicinskog fakulteta Sveučilišta u Zagrebu
    City: 10000 - Zagreb, Croatia

  2. Name of project: 3-01-199 Značenje P-fimbrija E.coli u određivanju terapije uroinfekta
    Name of institution: Znanstvena jedinica bolnice "Sveti Duh"
    City: 10000 - Zagreb, Croatia

  3. Name of project: 3-01-483 Utjecaj poremećaja mineralnog metabolizma na morfologiju i funkciju srca u uremiji
    Name of institution: Znanstvena jedinica Bolnice Sveti Duh
    City: 10000 - Zagreb, Croatia

  4. Name of project: 3-01-147 Uloga guanidina i purina u etiologiji dijabetesa
    Name of institution: Zavod za dijabetes
    City: 10000 - Zagreb, Croatia

COOPERATION - INSTITUTIONS


  1. Name of institution: Zavod za anatomiju Medicinskog fakulteta Sveučilišta u Zagrebu
    Type of institution: Economical/Production
    City: 10000 - Zagreb, Croatia

  2. Name of institution: Zavod za dijabetes Medicinskog fakulteta u Zagrebu
    Type of institution: University/Faculty
    Type of cooperation: Joint publishing of scientific papers
    City: 10000 - Zagreb, Croatia

  3. Name of institution: Zavod za farmakologiju Medicinskog fakulteta
    Type of institution: University/Faculty
    Type of cooperation: Systematic exchange of information
    City: 10000 - Zagreb, Croatia

  4. Name of institution: Zavod za farmakologiju Farmaceutskog fakulteta
    Type of institution: University/Faculty
    Type of cooperation: Systematic exchange of information
    City: 10000 - Zagreb, Croatia

  5. Name of institution: Institut za medicinska istraživanja
    Type of institution: State institute
    Type of cooperation: Occasional exchange of information
    City: 10000 - Zagreb, Croatia
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Last update: 10/16/95
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