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Title: End stage renal disease serum contains a specific renal cell growth factor

Abstract

End stage renal disease (ESRD) kidneys display abnormal growth characterized by a continuum of cystic disease, adenoma and carcinoma. This study evaluates the hypothesis that serum of patients with ESRD contains increased amounts of a growth factor which specifically induces proliferation of renal cells. ESRD sera compared to sera from normal controls induced a two to three-fold increase in the proliferative rate of renal cell carcinoma cell lines and normal kidney explants compared to cell lines from other sites. The increased proliferative activity of ESRD sera on renal cells was paralleled by an increase in cytosolic free calcium. The growth factor activity was encoded by a polypeptide of between 15 and 30 kd. The activity of ESRD sera on renal cells was not mimicked or inhibited by epidermal growth factor, basic fibroblast growth factor and platelet derived growth factor indicating that the renal cell specific growth factor activity in ESRD is different from these factors.

Authors:
; ;  [1]
  1. (Univ. of Toronto, Ontario (Canada))
Publication Date:
OSTI Identifier:
6271969
Resource Type:
Journal Article
Resource Relation:
Journal Name: Journal of Urology; (USA); Journal Volume: 145:1
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; ANIMAL CELLS; CELL PROLIFERATION; GROWTH FACTORS; BIOCHEMICAL REACTION KINETICS; UROGENITAL SYSTEM DISEASES; PATHOGENESIS; CALCIUM ISOTOPES; CARCINOMAS; KIDNEYS; PATIENTS; THYMIDINE; TRACER TECHNIQUES; TRITIUM COMPOUNDS; ALKALINE EARTH ISOTOPES; AZINES; BODY; DISEASES; HETEROCYCLIC COMPOUNDS; HYDROGEN COMPOUNDS; ISOTOPE APPLICATIONS; ISOTOPES; KINETICS; MITOGENS; NEOPLASMS; NUCLEOSIDES; NUCLEOTIDES; ORGANIC COMPOUNDS; ORGANIC NITROGEN COMPOUNDS; ORGANS; PROTEINS; PYRIMIDINES; REACTION KINETICS; RIBOSIDES; 550901* - Pathology- Tracer Techniques

Citation Formats

Klotz, L.H., Kulkarni, C., and Mills, G.. End stage renal disease serum contains a specific renal cell growth factor. United States: N. p., 1991. Web.
Klotz, L.H., Kulkarni, C., & Mills, G.. End stage renal disease serum contains a specific renal cell growth factor. United States.
Klotz, L.H., Kulkarni, C., and Mills, G.. Tue . "End stage renal disease serum contains a specific renal cell growth factor". United States. doi:.
@article{osti_6271969,
title = {End stage renal disease serum contains a specific renal cell growth factor},
author = {Klotz, L.H. and Kulkarni, C. and Mills, G.},
abstractNote = {End stage renal disease (ESRD) kidneys display abnormal growth characterized by a continuum of cystic disease, adenoma and carcinoma. This study evaluates the hypothesis that serum of patients with ESRD contains increased amounts of a growth factor which specifically induces proliferation of renal cells. ESRD sera compared to sera from normal controls induced a two to three-fold increase in the proliferative rate of renal cell carcinoma cell lines and normal kidney explants compared to cell lines from other sites. The increased proliferative activity of ESRD sera on renal cells was paralleled by an increase in cytosolic free calcium. The growth factor activity was encoded by a polypeptide of between 15 and 30 kd. The activity of ESRD sera on renal cells was not mimicked or inhibited by epidermal growth factor, basic fibroblast growth factor and platelet derived growth factor indicating that the renal cell specific growth factor activity in ESRD is different from these factors.},
doi = {},
journal = {Journal of Urology; (USA)},
number = ,
volume = 145:1,
place = {United States},
year = {Tue Jan 01 00:00:00 EST 1991},
month = {Tue Jan 01 00:00:00 EST 1991}
}
  • Children with ESRD, age 5-19 years, were supplemented with zinc acetate (2 mg/kg BW, maximum 40 mg/da/child) to determine if zinc supplements (ZS) would improve growth and bone maturation. Twelve children completed the study. Three of the 12 did not receive ZS. Seven of the 9 ZS children were followed for 1 year pre- and 1 yr during-ZS. Two subjects were followed for shorter periods of time. Heights, weights, and hand wrist radiographs were taken at the beginning of the study, just pre-ZS, and at the end of the study. Blood was analyzed for serum alkaline phosphatase and albumin monthly.more » Alkaline phosphatase was elevated in 7 of 12 subjects pre-ZS and in 5 of 9 subjects post-ZS. Albumin levels were below normal in 7 subjects pre-ZS and 4 subjects post-ZS. Mean plasma Zn and Cu levels, 97+/-17 and 164+/-42 mcg/dl, pre-ZS, and 102+/-30 and 173+/-46 mcg/dl post-ZS, respectively, were similar. Growth velocity in males (4.1+/-2.2 cm/yr, 3.0+/-2.3 cm/yr) and females (3.9+/-0.7, 3.3+/-2.1 cm/yr) pre- and post-ZS, respectively, were similar. Bone maturation per chronological age improved after ZS in 4 of 6 subjects, 1 matured at the same rate, and one at a slower rate. It appears that ZS of children with ESRD increased the rate of bone maturation but not linear growth.« less
  • Low cell calcium level is essential for preservation of red blood cell (RBC) membrane deformability and survival. RBCs from patients with end-stage renal disease (ESRD) demonstrate reduction in membrane deformability, possibly as a result of increased RBC cellular calcium level. To evaluate calcium homeostasis in RBCs from patients with ESRD, we measured cell calcium level, basal and calmodulin-stimulated calcium-stimulated Mg-dependent ATPase (CaATPase) activity, and calcium 45 efflux were measured before and after hemodialysis. The in vitro effect of uremic plasma and of urea on CaATPase activity of normal RBCs was tested, and 45Ca influx into RBCs of patients undergoing hemodialysismore » also was determined. A morphologic evaluation of red cells from patients with ESRD was performed with a scanning electron microscope. RBC calcium level in patients (mean +/- SEM 21.2 +/- 2.8 mumol/L of cells; n = 28) was higher than in controls (4.9 +/- 0.3 mumol/L of cells; n = 24; p less than 0.001). Hemodialysis had no effect on cell calcium level. Both basal and calmodulin-stimulated RBC CaATPase activities in patients with ESRD (n = 9) were reduced by approximately 50% (p less than 0.01), but after hemodialysis, enzyme activity returned to normal. 45Ca efflux from calcium-loaded cells, which was 2574.0 +/- 217.0 mumol/L of cells per 0.5 hours before hemodialysis, increased to 3140.7 +/- 206.8 mumol/L of cells per 0.5 hours after hemodialysis (p less than 0.005). In vitro incubation of normal RBCs with uremic plasma depressed CaATPase activity, but incubation with urea had no effect. RBCs of patients with ESRD revealed increased 45Ca influx, 7.63 +/- 1.15 mumol/L of cells per hour versus 4.61 +/- 0.39 mumol/L of cells per hour (p less than 0.025). RBCs of patients revealed a high incidence of spherocytosis and echynocytosis, which correlated with a high cell calcium level (r = 0.894, p less than 0.01).« less
  • This study assessed the usefulness of thallium stress testing as a predictor of perioperative cardiovascular risk in diabetic patients with end-stage renal disease undergoing cadaveric renal transplantation. Demographic factors influencing the exercise performance in these patients were also examined. The medical records of 189 consecutive patients with diabetic nephropathy who were evaluated for cadaveric renal transplantation were reviewed. Thallium stress testing was the initial examination of cardiovascular status in 141 patients. An adequate examination was one in which at least 70% of maximum heart rate was achieved. A thallium stress test was normal if there were no ST segment depressionsmore » on the electrocardiogram and no perfusion abnormalities on the thallium scan. Forty-four patients underwent cardiac catheterization as the initial evaluation (Group C) and four patients underwent transplantation without a formal cardiovascular evaluation (Group D). Sixty-four of the 141 patients undergoing thallium stress testing had an adequate and normal examination (Group A). The incidence of perioperative cardiac events in this group was 2%. Seventy-seven patients (Group B) had an abnormal (n = 41) or an inadequate (n = 36) thallium stress test and most (n = 61) then underwent coronary angiography. The use of beta-blockers was the only predictor of an abnormal or inadequate thallium stress test. Forty-three percent of patients with inadequate or abnormal thallium stress tests had significant coronary artery disease on cardiac catheterization. The perioperative risk of cardiac events was not different in Group A versus Groups B, C, and D combined. Survival of Group A and B patients was not different but was significantly longer than that of Group C patients.« less
  • Eighty patients with type I diabetes and end stage renal disease were prospectively evaluated for coronary artery disease with dipyridamole-thallium-201 scintigraphy and quantitative coronary angiography. Forty patients received dipyridamole orally, and 40 received it intravenously. The prevalence of coronary artery disease was 53%. There were no significant differences in the accuracy of the two dipyridamole tests (sensitivity = 85%, specificity = 85%, accuracy = 85% for the oral group; sensitivity = 86%, specificity = 72%, accuracy = 79% for the intravenous group). Combining the 80 patients into a single group gave a sensitivity of 86%, a specificity of 79%, andmore » an accuracy of 83% for the detection of coronary disease. Although the accuracy of this test in this patient population was similar to that previously reported for other groups, the prevalence of disease was high and resulted in a low predictive value of a negative test (83%).« less
  • The efficacy of dipyridamole single photon emission computed tomography (SPECT) thallium as a screening test for coronary artery disease (CAD), was studied in 45 patients with end-stage renal failure undergoing evaluation for renal transplantation. Coronary arteriography, dipyridamole SPECT thallium imaging and clinical follow-up were performed in all patients. Nineteen patients (42%) had an obstruction of 50% or more in at least one coronary artery. Fourteen patients had a positive thallium scan, but 7 of these were false-positives (sensitivity 37%, specificity 73%). The sensitivity was considerably lower than that quoted for non-ESRF patients in the literature, and significantly lower than amore » control group of 19 patients without ESRF having comparable severity and distribution of CAD. Five of the 6 patients who died of cardiac causes over a mean follow-up period of 25 months had normal thallium imaging, but all had significant coronary artery disease at cardiac catheterization. Dipyridamole SPECT thallium imaging has not proved a useful screening test for angiographically significant CAD, and does not predict cardiac prognosis in this population.« less