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Biomedical subjects

F Dumler

Publications and source records attributed to F Dumler.

At least 19 recordsLinked to original sources
PubMed1997

Gynecologic and reproductive issues in women on dialysis.

Most women on dialysis are amenorrheic and do not ovulate, but little information about menstrual patterns in women on dialysis exists, especially since the introduction and use of recombinant human erythropoietin, a therapy that may improve sexual interest and function. In this study, women who were < or = 55 years of age at the start of dialysis (n = 76) completed questionnaires and form the study group. Women older than 55 years at the start of dialysis did not complete the entire questionnaire (n = 115), but their medication records were reviewed for estrogen replacement therapy. The questionnaire asked about pregnancies, menstrual periods (regularity, frequency, duration, character of flow, menopause), and menopause before beginning dialysis and currently. Women also responded to questions about sexual activity, use of birth control, contraception counseling by physicians, yearly Papanicolaou smears, and mammograms. Demographic data (age, race, age at the time dialysis started, mode of dialysis, use of recombinant human erythropoietin, and history of renal transplant) were also obtained through the questionnaires. Fifty-nine percent of the 76 women who completed the study were white and had been on dialysis a median of 3 years (range, 0.1 to 18 years). The median age was 43 years, 68% were on hemodialysis, 90% were receiving recombinant human erythropoietin, and 70% had been pregnant (a total of 179 pregnancies; four pregnancies in four women occurred after the start of dialysis). Significantly more women were menstruating before dialysis started than currently (63% v 42%; P < 0.025), but the difference could be explained by patient age: currently menstruating women were younger (37 +/- 9 v 46 +/- 11 years; P = 0.0002). More women reported menstrual regularity before beginning dialysis (75% v 42% currently; P < 0.005), but there were no differences in number of days between or number of days of menstruation before beginning dialysis and currently. Menstrual flow was reported as heavier currently by more women (64% heavy flow with clots v 38% before dialysis started; P < 0.05). The median age at menopause was 47 years; 28% of the women were postmenopausal. Fifty percent of the women were sexually active, but only 36% used birth control. Discussions between the women and their nephrologist about possible pregnancy and contraception were reported by only 13% of women. Sixty-three percent of the women reported having yearly Papanicolaou smears and 73% had had a mammogram. Only 5% of the 113 women who were older than 55 years when they began dialysis were receiving estrogen replacement therapy. Amenorrhea was reported in this study by a smaller proportion of women than in studies conducted before the introduction of recombinant human erythropoietin. The possibility that erythropoietin may restore normal hormonal cyclic function in women with end-stage renal disease requires further study. Nephrologists as well as primary care physicians and gynecologists need to focus more on the gynecologic concerns of women on dialysis, including the potential for pregnancy. The effects of estrogen replacement on atherosclerosis and osteoporosis, and consideration of such therapy in women on dialysis warrants attention.

Adolescent↗
PubMed1996

Impact of peritoneal dialysis modality on nutritional and biochemical parameters.

Several lines of evidence suggest that continuous ambulatory peritoneal dialysis (CAPD) and continuous cycling peritoneal dialysis (CCPD) may differ in glucose, amino acid, and protein mass transfer. Thus, depending on modality, variances in protein and caloric balance could affect nutritional parameters. We prospectively followed 58 patients on CAPD (n = 36) or CCPD (n = 22) for 21 months (age: 54 +/- 14 years; weight: 76 +/- 16 kg; body mass index: 25.8 +/- 5.1 kg/m2). Twenty-four-hour dialysate effluent (Kpt/V) and normalized protein catabolic rate values were comparable in both CAPD and CCPD patients (0.23 +/- 0.05 vs 0.20 +/- 0.05 and 0.93 +/- 0.23 vs 0.87 +/- 0.21 g/kg/day, respectively). At the last trimester, CAPD patients had greater body weight and body mass index increases than those on CCPD (1.6 +/- 1.1 vs 0.3 +/- 1.1 kg and 0.53 +/- 0.42 vs 0.06 +/- 0.35 kg/m2, respectively), which did not reach statistical significance. No differences were noted in serum protein, albumin, or cholesterol levels (6.5 +/- 0.1 vs 6.5 +/- 0.2 g/dL; 3.5 +/- 0.1 vs 3.7 +/- 0.1 g/dL; and 211 +/- 10 vs 209 +/- 10 mg/dL for CAPD and CCPD, respectively). In summary, this study demonstrates that CAPD and CCPD, when delivered in equal amounts, result in similar weight gains and maintain comparable biochemical nutritional parameters.

Adult↗
PubMed1996

Impact of acidosis on nutritional status in chronic peritoneal dialysis patients.

Malnutrition is a well-recognized risk factor for survival in chronic dialysis patients. Experimental evidence links acidosis to decreases in albumin synthesis and increased breakdown. We studied serum bicarbonate, albumin, and total protein concentrations in 79 peritoneal dialysis patients (mean age 53 +/- 14 years) during a 21-month observation period. No changes were observed in blood urea nitrogen (66 +/- 19 vs 61 +/- 18 mg/dL), serum creatinine (9.8 +/- 4.5 vs 10.7 +/- 4.5 mg/dL), serum bicarbonate (25 +/- 3 vs 25 +/- 3 mEq/L), anion gap (16 +/- 3 vs 17 +/- 3 mEq/L), and serum albumin (3.6 +/- 0.6 vs 3.6 +/- 0.6 g/dL) concentrations between the first and last trimester of follow-up. A poor correlation was also found between serum albumin concentration and anion gap (R = -0.373) and bicarbonate (R = -0.172) concentrations. Finally, when grouped by acid-base status, serum protein (6.5 +/- 0.7 vs 6.5 +/- 0.8 g/dL) and albumin (4.0 +/- 0.4 vs 3.9 +/- 0.4 g/dL), concentrations were similar in patients with serum bicarbonate levels < or > or = 22 mEq/L, respectively. In conclusion, a mild to moderate degree of acidosis is not associated with decreases in serum albumin concentrations in stable chronic peritoneal dialysis patients.

Acid-Base Equilibrium↗
PubMed1995

Vancomycin removal by high-flux polysulfone hemodialysis membranes in critically ill patients with end-stage renal disease.

To define the pharmacokinetics of vancomycin in patients undergoing maintenance hemodialysis in an acute care setting and to characterize the rebound phenomenon occurring after hemodialysis, vancomycin t1/2 during the interdialytic and intradialytic phases and intradialytic clearance were measured in eight critically ill patients undergoing high-flux hemodialysis using F-80 or F-60 polysulfone dialyzers. Intradialytic clearance was determined using the recovery method. In patients dialyzed with F-80 dialyzers, interdialytic and intradialytic t1/2 for vancomycin were 162 +/- 69.8 hours and 4.7 +/- 1.3 hours, respectively. Intradialytic clearance was 108.5 +/- 16.3 mL/min, and 238 +/- 55 mg of vancomycin was recovered in the dialysate. In patients dialyzed with F-60 dialyzers, interdialytic and intradialytic t1/2 were 211.0 +/- 166.8 and 4.6 +/- 0.4 hours, respectively. Intradialytic clearance was 100.6 +/- 18.3 mL/min and the amount of vancomycin recovered was 252 +/- 79 mg. Vancomycin concentrations rebounded by 16% to 37% between 3 and 6 hours in patients dialyzed with the F-80 dialyzer and 15% to 38% between 2 and 3 hours in patient dialyzed with F-60 dialyzers. Hemodialysis with high-flux polysulfone dialyzers removes significant amounts of vancomycin in patients dialyzed in an acute care setting. A suggested scheme for vancomycin dosage adjustments in these patients is presented.

Adult↗
PubMed1995

Electrolyte disturbances in elderly patients with severe diarrhea due to cholera.

The purpose of this clinical study was to evaluate prospectively electrolyte disturbances in elderly patients with severe diarrhea due to cholera. A total of 20 adult (Group I; < 60 yr) and 22 elderly (Group II; > or = 60 yr) patients were studied. In all patients, extracellular fluid (ECF) volume reexpansion was achieved with normal saline at 50 mL/kg per hour. Once a diuresis of 40 mL/h was achieved, intravenous therapy was discontinued and patients' ECF volumes were reexpanded orally with a polyelectrolyte solution. Blood and urine samples were obtained on admission, at the time when adequate diuresis ensued, and after 12 h of oral ECF volume reexpansion. On admission, both groups had severe ECF volume contraction but only mild increases in osmolality (308 +/- 12 and 310 +/- 13 mosmol/kg for Groups I and II respectively; P = NS). Acidemia (pH) was equally severe in both (Group I: 7.13 +/- 0.11; Group II: 7.11 +/- 0.09; P = NS), and the anion gap was comparably increased in both groups (30 +/- 8 and 26 +/- 7 mmol/L for Groups I and II, respectively; P = NS). None of the patients was hypokalemic at the time of admission (Group I: 4.3 +/- 0.5 mmol/L; Group II: 4.5 +/- 0.5 mmol/L; P = NS). Adequate diuresis was achieved at 2.0 +/- 0.7 h in both groups. At the end of the rapid ECF volume reexpansion phase, the anion gap normalized in both groups (Group I: 15.6 +/- 3.7 mmol/L; Group II: 14.4 +/- 2.8 mmol/L; P = NS), and serum potassium concentrations remained normal (Group I: 4.4 +/- 0.4 mmol/L; Group II: 4.1 +/- 0.4 mmol/L; P = NS). We conclude that use of aggressive intravenous hydration with normal saline followed by oral ECF volume reexpansion allows prompt correction of electrolyte abnormalities in adult and elderly patients with severe diarrhea as a result of cholera.

Adolescent↗
PubMed1995

Thyroid function surveillance in CAPD patients.

We monitored thyroid function in 75 peritoneal dialysis patients (55 +/- 15 years). A total of 20 (27%) were hypothyroid; 9 were diagnosed about the time of initiation of dialysis, and 11 prior to onset of renal failure. Thyroid function surveillance found an increase in serum thyrotropin (TSH) concentration to hypothyroid values in only one patient. On replacement therapy serum thyroxine was similar in euthyroid and hypothyroid patients (6.94 +/- 1.69 vs 6.52 +/- 1.65 micrograms/dL, respectively; p = 0.380), but TSH was higher in hypothyroid patients (5.61 +/- 5.67 vs 2.59 +/- 1.49 microU/mL, respectively; p = 0.001). Serum creatinine (8.6 +/- 3.1 vs 11.4 +/- 5.1 mg/dL, respectively; p = 0.049) and albumin concentrations (3.76 +/- 0.47 vs 3.33 +/- 0.71 g/dL, respectively; p = 0.006) were lower in hypothyroid than euthyroid patients. Hyperthyroid patients had higher serum triglyceride concentrations than euthyroid patients (306 +/- 176 vs 189 +/- 122 mg/dL, respectively; p = 0.013). Parathyroid hormone (PTH) was lower in hypothyroid than normothyroid patients (108 +/- 80 vs 261 +/- 265 pg/mL, respectively; p = 0.032). No differences were observed in serum calcium, phosphorus, and alkaline phosphatase. We conclude that hypothyroidism is common in peritoneal dialysis patients, usually antedates dialysis therapy, results in lower serum albumin and creatinine concentrations and higher serum triglyceride concentrations, is associated with lower serum PTH concentrations, and that thyroid function surveillance is not necessary in the absence of symptoms suggestive of hypothyroidism.

Alkaline Phosphatase↗
PubMed1995

The method used for volume estimation significantly influences KprT/V results in peritoneal dialysis patients.

We studied 51 patients (age 50 +/- 15 years; weight 75 +/- 17 kg; blood urea nitrogen 62 +/- 20 mg/dL), 61% of whom were obese. The volume of distribution of urea was estimated by anthropometric formulas (Watson and Hume) and as 58% of actual and ideal body weight. Volumes derived from use of 58% of actual body weight were highest (43.4 +/- 10.0 kg; p = 0.0005); no differences were noted between Watson and Hume volumes and those obtained using 58% of ideal body weight (38.5 +/- 8.0, 39.4 +/- 7.5, and 37.0 +/- 5.6 kg, respectively). Normalized daily urea clearance (KprT/V) was lowest and highest when using 58% of actual and ideal body weight, respectively (0.251 +/- 0.081 and 0.290 +/- 0.091; p < 0.0001). KprT/V values derived using the Watson and Hume methods were similar (0.279 +/- 0.081 and 0.274 +/- 0.083, respectively), but significantly lower than those obtained using actual body weight (p < 0.0001). Differences were magnified in obese patients. A subset of patients underwent hemodialysis for urea volume measurement by urea kinetic modeling. Volume estimates using bioelectrical impedance showed the least bias when compared to values calculated during a hemodialysis treatment. We conclude that KprT/V is very dependent on body habitus and the method used for volume determination. Standardization of the volume parameter is essential to defining therapeutic guidelines and for meaningful comparisons between centers.

Body Composition↗
PubMed1993

Predictability of creatinine clearance estimates in critically ill patients.

OBJECTIVES: a) To evaluate the predictive ability of different creatinine clearance methods as compared with the criterion standard, inulin clearance; and b) to determine which of the predictive methods yields the most accurate estimation of creatinine clearance. DESIGN: Prospective study. SETTING: Medical intensive care unit (ICU) of a university-affiliated tertiary care hospital. INTERVENTIONS: Glomerular filtration rate was measured by the criterion standard, inulin clearance. PATIENTS: Twenty mechanically ventilated adults. MEASUREMENTS: Renal function was assessed by the following procedures: inulin clearance using a standard protocol, 30-min creatinine clearance, 24-hr creatinine clearance, and creatinine clearance estimates by the Cockcroft-Gault equation. Ideal body weight, total body weight or lean body mass with actual serum creatinine or serum creatinine concentration corrected to 1 mg/dL (85 mumol/L) in cachectic patients were sequentially incorporated into the Cockcroft-Gault equation. RESULTS: The Cockcroft-Gault equation, using ideal body weight and the corrected serum creatinine concentration, was the best predictor of inulin clearance with the smallest bias (9.7 +/- 8.6, 95% confidence interval 5.7 to 13.8). The bias encountered with the 30-min creatinine clearance was not different from that value with the 24-hr creatinine clearance (21.6 +/- 33.0, 95% confidence interval 6.2 to 37.1 vs. 25.4 +/- 28.3, 95% confidence interval 11.8 to 42.9). Good correlations existed between inulin clearance and the Cockcroft-Gault equation, using ideal body weight and the corrected serum creatinine concentration (r2 = .81; p = .0001), as well as between inulin clearance and the Cockcroft-Gault equation, using the lower of ideal or total body weight and the higher of the actual serum creatinine concentration or corrected serum creatinine (r2 = .75; p = .0001). The 30-min creatinine clearance and the 24-hr creatinine clearance had poorer agreement with inulin clearance. The incorporation of a corrected serum creatinine value into the Cockcroft-Gault equation consistently led to better predictions and higher correlation coefficients. CONCLUSIONS: The utilization of the Cockcroft-Gault equation as used clinically (the lower of ideal or total body weight and the higher of actual serum creatinine or corrected serum creatinine concentration to 1 mg/dL [85 mumol/L]) results in more accurate predictions of glomerular filtration rate in the medical, critically ill patient than urine creatinine clearance measures. If creatinine clearance measures are used, the 30-min collection provided results not different from those results obtained with 24-hr urinary collections.

Adult↗
PubMed1993

Influence of the pretransplant hematocrit level on early graft function in primary cadaveric renal transplantation.

Although use of human recombinant erythropoietin has alleviated symptoms of anemia in renal failure, effects of increased hematocrit (HCT) on early post-transplant renal function are unknown. Of 244 consecutive primary cadaveric kidney recipients transplanted over 74 months, 43% had HCT > or = 30% and 57% had HCT < 30% at transplantation. The incidence of delayed graft function (DGF) was greater in recipients with HCT > or = 30% (61%) than in recipients with HCT < 30% (33%; P = 0.0001). Ten percent of recipients with HCT > or = 30% experienced primary nonfunction (PNF) of the allograft (P = 0.0001). No recipient with HCT < 30% had PNF. Absolute rises in HCT over the 3 months preceding transplantation were greatest in those with PNF (2.5 +/- 2.4) followed by those with DGF (2.0 +/- 3.1) and immediate graft function (IGF) (0.2 +/- 5.2; P = 0.0328). Logistic regression analysis identified HCT > or = 30% (P = 0.0014), cold storage > or = 24 hr (P = 0.0006) and rising HCT (P = 0.0090) as independent predictors of DGF with relative risks of 3.1-, 3.3-, and 2.7-fold, respectively. Recipients with rising pretransplant HCTs who underwent dialytic fluid removal within 24 hr before transplantation had DGF with greater frequency (67%) than nondialyzed recipients with rising HCTs (45%). Primary cadaveric kidney recipients with HCT > or = 30% at transplantation have significantly greater risk for DGF and PNF. Rising pretransplant HCT levels may predispose recipients to DGF; this risk may be heightened in those undergoing hemodialysis shortly before transplantation.

Adult↗
PubMed1993

Indirect measures of total body water may confound precise assessment of peritoneal dialysis adequacy.

Urea kinetic modeling (UKM) has yet to be optimized as a practical tool for assessing adequacy of therapy in continuous ambulatory peritoneal dialysis (CAPD) patients. Watson equation (WV) and 58% body weight (58%WT) estimates of total body water (TBW) are indirect measures likely to yield imprecise estimates of Kt/V. Bioelectrical impedance (BEI) measures body composition as a function of electrical conductance, minimizing fat contribution to TBW. TBW values were highest when measured as 58% WT and lowest when calculated from WV. These differences were most striking in patients with overweight body habitus. BEI-derived TBW correlated best with UKM values. The relationship between BEI-derived and anthropometrically derived TBW was best in patients of normal habitus. Kt/V values were highest when calculated from WV-derived volumes and significantly differed from Kt/V values calculated from BEI-derived and 58%WT volumes. When segregated by habitus, however, only in overweight patients was this pattern of clinical significance. Serial body weight, lean body mass, and TBW remained stable in patients of normal habitus. Overweight patients increased weight by 5%, lean mass by 2%, and TBW by 5%, 3%, and 2% when measured by 58%WT, WV, and BEI respectively. BEI measures of TBW exclude fat mass and thus strengthen the use of Kt/V for assessing dialysis adequacy in CAPD patients of all body weights.

Adult↗
PubMed1993

Abbreviated method for urea kinetic modeling in continuous ambulatory peritoneal dialysis patients.

Urea kinetic modeling (UKM) is an established method for quantitating hemodialysis, with target values clearly defined. Precise methods for measuring continuous ambulatory peritoneal dialysis (CAPD) prescriptions are less well-defined, and 24-hour collections of dialysate effluent are logistically impractical. UKM parameters derived from an abbreviated (4-hour) collection period were compared with simultaneously obtained 24-hour collections of urine and dialysate effluent in 22 CAPD patients. Daily Kt/V was calculated from total (residual renal and peritoneal) urea clearance and an anthropometric-derived total body water volume. Results yielded from the 24-hour collection included a mean Kt/V of 0.29 +/- 0.09, and mean protein catabolic rate (PCR) of 0.84 +/- 0.24 g/kg/day. Daily Kt/V values were calculated from each individual dialysate cycle. The first morning cycle after an overnight dwell correlated best with results obtained using 24-hour collections (r = 0.921; p < 0.0001) with no significant differences in Kt/V found (p = 0.454) between the short and 24-hour methods. Daily Kt/V values converted by exponential transformation to a thrice-weekly hemodialysis value yielded a Kt/V equivalent of 1.02 +/- 0.40. UKM using an abbreviated collection period is an accurate and practical tool for quantitating CAPD adequacy in a routine clinical setting.

Blood Urea Nitrogen↗
PubMed1993

Effective continuous ambulatory peritoneal dialysis following abdominal aortic aneurysm repair.

OBJECTIVE: To review a single center's experience with the initiation and maintenance of continuous ambulatory peritoneal dialysis (CAPD) in 8 patients with a history of abdominal aortic aneurysm repair (AAAR). DESIGN: Retrospective case review with long-term follow-up. PATIENTS (OR PARTICIPANTS): Eight patients with multiple medical problems including a history of abdominal aortic aneurysm repair and end-stage renal failure who received peritoneal dialysis catheters between December 1986 and July 1991. MAIN OUTCOME MEASURES: Success of catheter implantation and maintenance of continuous ambulatory peritoneal dialysis; incidence of peritoneal infection and long-term complications; overall clinical course. RESULTS: Over five years 8 patients with a history of reconstructed abdominal aortic aneurysm received peritoneal dialysis catheters without complication and dialyzed successfully for 88 patient-months in total. Three patients had a total of five episodes of peritonitis, at an incidence of 0.68 episodes per patient per year, a rate not significantly different from that of our overall CAPD patient population (1.09) and that reported by other groups. CONCLUSION: Our experience suggests that historical AAAR poses no significant risk to and should not preclude the implementation of continuous ambulatory peritoneal dialysis. Indeed, CAPD offers a safe and optimal dialytic alternative for patients with historical abdominal aortic aneurysm repair in whom compromised cardiovascular hemodynamics may significantly influence morbidity and survival.

Aged↗
PubMed1992

Clinical experience with short-time hemodialysis.

After at least 6 months on conventional hemodialysis (cellulosic dialyzers, acetate dialysate, and a 3- to 4-hour treatment time), 56 patients were changed to short-time hemodialysis (less than 180 minutes) using polysulfone dialyzers and bicarbonate-containing dialysate. Treatment time decreased (191 +/- 5 v 147 +/- 5 min; P = 0.001), while Kt/V (1.22 +/- 0.04 v 1.29 +/- 0.06; P = NS) and normalized protein catabolic rate (pcr) (1.10 +/- 0.05 v 1.10 +/- 0.07 g/kg/d; P = NS) remained constant. When compared with the conventional period, 30 months of short-time hemodialysis resulted in no changes in predialysis blood pressure (BP) (151 +/- 2/84 +/- 1 v 151 +/- 2/86 +/- 1 mm Hg), postdialysis BP (144 +/- 2/81 +/- 1 v 143 +/- 3/84 +/- 1 mm Hg), interdialytic weight gain (2.4 +/- 0.1 v 2.7 +/- 0.2 kg), or blood urea nitrogen (BUN) (26.1 +/- 0.71 v 25.3 +/- 1.07 mmol/L [73 +/- 2 v 71 +/- 3 mg/dL]). Shorter treatment times were not associated with an increase in intradialytic complications. Actually, the frequency (%) of dialysis treatments associated with nausea (5.94 +/- 1.33 v 2.21 +/- 0.52), vomiting (3.12 +/- 0.87 v 0.54 +/- 0.14; P less than 0.05), headaches (5.60 +/- 1.13 v 2.03 +/- 0.52; P less than 0.05), and back pain (0.91 +/- 0.25 v 0.05 +/- 0.05; P less than 0.05) was decreased.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetates↗
PubMed1992

Mesangial cell killing by leukocytes: role of leukocyte oxidants and proteolytic enzymes.

Mesangial cells from human and rat kidney were examined for sensitivity to killing by neutrophils. Cells from both species were sensitive to killing by phorbol myristate acetate-stimulated neutrophils. Catalase was highly protective while superoxide dismutase was less protective and a number of protease inhibitors were not protective. Strong protection was also observed with the iron chelators, deferoxamine and phenanthroline, and with the hydroxyl radical scavengers, dimethylthiourea and 5,5-dimethyl-1-pyrroline N-oxide. Pretreatment of the mesangial cells with deferoxamine followed by washing also provided protection. Mesangial cells were also killed by reagent hydrogen peroxide (H2O2) but were much less sensitive to injury by direct application of proteolytic enzymes. The ability of H2O2 to injure mesangial cells was prevented by pre-incubation of the H2O2 with human leukocyte myeloperoxidase. These data suggest that killing is due primarily to the generation of H2O2 by the stimulated neutrophils and its further reduction in an iron-catalyzed reaction. The hydroxyl radical may be the reduction product that actually mediates lethal injury but lack of scavenger specificity prevents definitively concluding this. Mesangial cell killing by activated neutrophils could be significantly inhibited by monoclonal antibodies to CD11/CD18 molecules, suggesting that close contact between the target and effector cells is required for cytotoxicity. Although qualitatively similar to endothelial cells, the mesangial cells appeared to be quantitatively more oxidant sensitive than previously examined human and rat endothelial cells. Taken together, these data show that mesangial cells from rat and human are sensitive to leukocyte-induced injury and that injury results via an oxidant pathway.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Intraglomerular pressure and mesangial stretching stimulate extracellular matrix formation in the rat.

To define the interplay of glomerular hypertension and hypertrophy with mesangial extracellular matrix (ECM) deposition, we examined the effects of glomerular capillary distention and mesangial cell stretching on ECM synthesis. The volume of microdissected rat glomeruli (Vg), perfused ex vivo at increasing flows, was quantified and related to the proximal intraglomerular pressure (PIP). Glomerular compliance, expressed as the slope of the positive linear relationship between PIP and Vg was 7.68 x 10(3) microns 3/mmHg. Total Vg increment (PIP 0-150 mmHg) was 1.162 x 10(6) microns 3 or 61% (n = 13). A 16% increase in Vg was obtained over the PIP range equivalent to the pathophysiological limits of mean transcapillary pressure difference. A similar effect of renal perfusion on Vg was also noted histologically in tissue from kidneys perfused/fixed in vivo. Cultured mesangial cells undergoing cyclic stretching increased their synthesis of protein, total collagen, and key components of ECM (collagen IV, collagen I, laminin, fibronectin). Synthetic rates were stimulated by cell growth and the degree of stretching. These results suggest that capillary expansion and stretching of mesangial cells by glomerular hypertension provokes increased ECM production which is accentuated by cell growth and glomerular hypertrophy. Mesangial expansion and glomerulosclerosis might result from this interplay of mechanical and metabolic forces.

Animals↗