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Biomedical subjects

T B Wiegmann

Publications and source records attributed to T B Wiegmann.

At least 37 records · Page 2Linked to original sources

In vitro effects of cyclosporine on glomerular function.

Cyclosporine A (CsA) causes vasoconstriction and decrease in glomerular filtration rate. Experiments were conducted in isolated glomeruli to study effects of CsA of glomerular perfusion and independent of systemic or renal factors. CsA caused a dose dependent decrease in glomerular volume consistent with mesangial contraction. The ultrafiltration coefficient Kf was significantly lower after incubation in 4 X 10(-4) M CsA when compared to control (2.81 +/- 0.2 vs 5.19 +/- 0.5 nl/min X mm Hg; p less than 0.001). Hydraulic conductivity Lp was diminished by CsA from 2.69 +/- 0.11 to 1.41 +/- 0.05 microliter/min X mm Hg X cm2 (p less than 0.001). These findings demonstrate a direct effect of CsA on the glomerulus which must be considered in addition to drug-induced changes in perfusion and tubular function.

Animals↗

Glomerular effects of angiotensin II require intrarenal factors.

Glomerular ultrafiltration coefficient (Kf) of glomeruli isolated from kidneys of normovolemic rats decreases following infusion of angiotensin II (ANG II). Kf from isolated glomeruli after ANG II infusion in vivo and from isolated perfused kidneys following infusion of ANG II in vitro was measured to determine whether the decrease required the presence of systemic factors. Filtration was induced in vitro and the maximum rate of change in glomerular volume was used to calculate Kf. Glomerular capillary hydraulic conductivity (Lp) was calculated from Lp = Kf/A where the basement membrane area A was calculated as 3 X pi X D2. ANG II infusion in vivo in rats diminished Lp from 3.19 +/- 0.19 to 1.96 +/- 0.13 and to 1.82 +/- 0.11 microliters.min-1.mmHg-1.cm-2, respectively. ANG II infusion into isolated kidneys caused a similar decrease in Lp (3.55 +/- 0.11 to 2.37 +/- 0.07). ANG II infusion either in vivo or during isolated kidney perfusion decreases Kf and Lp. ANG II effects do not require the presence of extrarenal factors but depend on perfusion in situ since incubation of isolated glomeruli with ANG II did not alter Kf.

Angiotensin II↗

Prediction of carcinoma in acquired cystic disease as a function of kidney weight.

Acquired renal cystic disease occurs in up to 80% of patients on chronic dialysis and is complicated by renal adenocarcinoma in about 6% of cases. This report suggests that acquired cystic kidneys weighing more than 150 g are six times more likely to contain carcinoma than are kidneys of smaller size. This relationship is true whether or not the large kidney contains a radiologically detectable tumor. Therefore, even in the absence of demonstrable tumor mass, strong consideration should be given to the removal of large acquired cystic kidneys.

Carcinoma, Renal Cell↗

Recognition of hypertension and abnormal blood pressure burden with ambulatory blood pressure recordings in type I diabetes mellitus.

Ambulatory blood pressure (AMBP) measurements were obtained at 20-min intervals for 24 h in 25 subjects with insulin-dependent (type I) diabetes mellitus and 21 control subjects. The diabetic patients had normal kidney function (glomerular filtration rate 112.1 +/- 7.2 ml.min-1.1.73 m-2, renal plasma flow 459.0 +/- 23.4 ml.min-1.1.73 m-2) and were normotensive according to standard sphygmomanometer examinations. Mean +/- SE AMBP (systolic/diastolic in mmHg) measurements in diabetic patients (24 h, 131.7/77.2 +/- 2.9/1.8; 0600-2200, 132.3/78.4 +/- 2.9/3.4; 2200-0600, 125.1/75.7 +/- 3.9/3.4) significantly exceeded control values during all times (24 h, 121.8/70.3 +/- 2.9/1.9; 0600-2200, 120.7/71.8 +/- 2.6/2.0; 2200-0600, 108.2/61.5 +/- 6.6/2.7). Mean 24-h AMBP exceeded 135/85 mmHg in 49% of diabetic patients. The same threshold of 135/85 mmHg was used to determine the prevalence of abnormal measurements per time period (pressure burden). Pressure burden was increased twofold in diabetic patients compared with control subjects. Mean AMBP was significantly reduced at night in control subjects but not in diabetic patients. Changes in blood pressure were not related to kidney function in diabetic patients. AMBP recordings uncovered an increased prevalence of abnormal mean blood pressure, increased pressure burden, and a lack of diurnal variation of blood pressure in subjects with type I diabetes mellitus. These findings have important implications for early intervention strategies in diabetes mellitus because AMBP recordings correlate well with end-organ damage.

Adult↗

Comparison of albumin excretion rate obtained with different times of collection.

This study was undertaken to assess the usefulness of different techniques for determination of albumin excretion rate (AER). Ninety patients with type I (insulin-dependent) diabetes mellitus and 45 with type II (non-insulin-dependent) diabetes mellitus, with AER/24 h of less than 200 micrograms/min, were included. All patients were free of major systemic complications of diabetes and overt kidney disease (mean serum creatinine 1.1 +/- 0.1 mg/dl, range 0.4-1.2 mg/dl). We compared timed day, night, and 24-h specimens, as well as timed spot specimens during water-induced diuresis. Most patients with type I (75 of 90) and type II (30 of 45) diabetes had AER less than 20 micrograms/min and showed significant differences in AER that were dependent on the collection time. Differences were diminished or absent with AER less than 20 micrograms/min. Sensitivity, specificity, and prediction rates of AER in different specimens were evaluated against 24-h AER. Use of albumin concentrations and albumin-creatinine ratios did not improve test performance in comparison with AER. Sampling time and the overall rate of AER influenced measurement of urinary albumin excretion. Day or 24-h AER is most useful to determine the presence of abnormal AER. AER and albumin concentration in spot samples are of limited use for initial screening and frequently require day or 24-h specimens of AER for confirmation. Day or 24-h AER should be used for long-term follow-up of the diabetic patient.

Adolescent↗

Malabsorption of calcium and phosphate in chronic renal failure: 32P and 45Ca studies in dialysis patients.

A modified double-isotope method was used to determine the absorption of calcium and phosphate in patients with chronic renal failure. Eight hemodialysis patients and six healthy control subjects received an intravenous dose of 45calcium and 32phosphate and an oral tracer dose of 45Ca and 32P was administered two weeks later. Timed plasma samples were obtained on each occasion to determine fractional absorption rates and cumulative absorption of either tracer from both tracer sets with deconvolution analysis. Stool collections were analyzed. Calcium absorption in normal subjects peaked at 12% over fifteen minutes at one hour and declined rapidly thereafter. Absorption was essentially complete at four hours and cumulative absorption at this time was 72 +/- 6%. The pattern of phosphate absorption was similar and cumulative absorption at 4 hours was 80 +/- 3%. Calcium absorption in dialysis patients was significantly impaired with a flattened profile, a maximal 15-min absorption rate of 2% and cumulative 4-h absorption of 20 +/- 2%. Phosphate absorption in dialysis patients was also impaired to a comparable degree with a maximal rate of 3.6% and a more delayed cumulative total of 35 +/- 5%. Stool data showed good agreement with deconvolution analysis in volunteers but always overestimated absorption in patients. Sequential double isotope analysis provided a simple and convenient method for the concurrent estimation of calcium and phosphate absorption in humans.

Aged↗

Urate excretion by the isolated perfused rat kidney and modification by drugs.

Urate excretion in the isolated perfused rat kidney was studied over a wide range of perfusate urate concentrations (13.9-376.8 microM). Fractional excretion of urate (FEurate) averaged 57.9 +/- 2.0% (range, 58.5-59.6%), showed marked interanimal variability, but was not dependent on the perfusate-free urate concentration. In paired experiments, the effects of five drugs (probenecid, pyrazinoate, furosemide, salicylate, and oxonate) on FEurate were evaluated. A low concentration of pyrazinoate (0.2 mM) decreased FEurate (62.0 +/- 1.9 vs 53.8 +/- 2.4%, P less than 0.05), as did 0.8 mM pyrazinoate (59.5 +/- 2.4 vs 48.4 +/- 2.7%, P less than 0.05). Probenecid (1 mM) decreased FEurate (59.3 +/- 3.1 vs 52.0 +/- 2.5%, P less than 0.05) but 2.5 mM probenecid did not alter FEurate (48.0 +/- 6.3 vs 47.8 +/- 6.9%). Oxonate (0.1 mM) also decreased FEurate (75.8 +/- 4.2 vs 67.1 +/- 2.1%, P less than 0.05) while 0.2 mM oxonate had no effect (66.4 +/- 3.5 vs 61.5 +/- 4.6%). Neither salicylate nor furosemide affected FEurate, although both drugs caused a saliuresis and diuresis. Thus, urate transport in rat kidneys in vitro is not dependent on urate concentration, unlike man. Some drugs known to affect urate excretion in humans and rats did not have similar effects in isolated kidneys. Isolated organ studies provide additional information is understanding renal urate handling.

Animals↗

Dialysis leukopenia, hypoxemia, and anaphylatoxin formation: effect of membrane, bath, and citrate anticoagulation.

The goal of these prospective studies was to determine the effect of different dialyzer membranes and dialysate composition on leukopenia and hypoxemia during hemodialysis with citrate anticoagulation. Significant early leukopenia was found with a cuprophane membrane, while a cellulose acetate membrane was associated with mild early leukopenia. Bath composition had no effect. Bicarbonate dialysate, compared with acetate, eliminated hypoxemia in cellulose acetate membranes and reduced its degree and duration with cuprophane. Membrane composition had no effect on hypoxemia during acetate dialysis. The findings indicate that leukopenia is directly and exclusively related to membrane composition while hypoxemia only relates in part to membrane effects. Serial determinations of complement components C3a and C5a showed significant increases in parallel with leukopenia during heparin anticoagulation, but the anaphylatoxin concentration changes were dissociated during dialysis with citrate anticoagulation. The concentrations of anaphylatoxins C3a and C5a appear not to be directly related to dialysis-induced leukopenia. The dissociation between anaphylatoxin concentrations and leukopenia may be related to changes in generation or unmasked changes in leukocyte response. Citrate anticoagulation may provide a useful probe for further studies on membrane-leukocyte interactions in vivo.

Acetates↗

Excretion of para-aminohippurate in the isolated perfused rat kidney: net secretion and net reabsorption.

1. The excretion of para-aminohippurate (PAH) in the isolated perfused rat kidney was examined over a wide range of perfusate PAH concentrations (15 microM to 6 mM). PAH excretion increased steadily over the range of perfusate concentrations, reaching a maximal excretion rate of 3.28 mumol/min at a free-PAH concentration of 6 mM. 2. Tubular transport of PAH was evaluated from the difference between ultrafiltered PAH and excreted PAH. Net PAH secretion was observed at low perfusate free PAH concentrations. Net PAH transport was zero at a perfusate free PAH concentration of 2.1 mM. Above this level there was progressive net reabsorption. 3. Probenecid (2.5 mM) decreased PAH secretion to 18% of the initial value at 129 microM-free PAH (P less than 0.05). Probenecid had no effect on net reabsorption of PAH at high perfusate levels of the anion. 4. Alanine (5 mM) decreased net PAH secretion by 50% at low free PAH concentrations (P less than 0.05) and decreased net PAH reabsorption by 50% at at a free PAH concentration of 6 mM (P less than 0.05). These effects could not be related to effects of PAH, probenecid or alanine on glomerular filtration rate (GFR), vascular resistance or electrolyte excretion. 5. The results confirm the existence and integrity of the proximal tubular organic anion secretory system in the isolated kidney. In addition, net PAH reabsorption occurs at high perfusate levels.

Absorption↗

Renal adenocarcinoma and acquired cystic disease in chronic hemodialysis patients.

Three chronic hemodialysis patients developed renal cell adenocarcinoma with evidence of acquired cystic disease in two. The incidence of renal cancer in this study population of 0.27% per year is 50 times greater than that expected in general. The cancers appeared to develop at different rates. In one patient examined by serial computed tomography (CT) over 2.5 years, the tumor progressed rapidly. In the other two patients, the process was more idolent. On the basis of our experience, we recommend that dialysis patients be screened for acquired cystic kidney disease (ACKD) and renal tumors by sonography or CT. Patients with ACKD should be observed at regular intervals by CT for the development of possible tumor.

Adult↗

Long-term comparisons of citrate and heparin as anticoagulants for hemodialysis.

Citrate was compared to heparin as an anticoagulant during chronic hemodialysis. A randomized crossover design was used in six stable male dialysis patients. There were no measurable crossover effects. Use of citrate as the sole anticoagulant for periods of 2 months was easily accomplished, free of complications, and resulted in comparable clearance of solutes. Major laboratory parameters were similar with both anticoagulants. Importantly, there was no significant citrate accumulation. The results also indicate that recurrent use of heparin during dialysis has no measurable effect on lipid metabolism in stable patients.

Anticoagulants↗

Percutaneous transluminal angioplasty in transplant renal artery stenosis: experience and review of the literature.

Percutaneous transluminal angioplasty (PTA) was performed in five instances of renal transplant artery stenosis (RTAS) in four patients. Hypertension was present in all cases and improved after angioplasty together with reduction in medicine requirements. Abnormal renal function in four instances also improved after PTA. This reflects the current literature in which 76 of 90 patients were successfully treated by PTA (follow-up to 24 months), with two cases of recurrent stenosis, no mortality, and only a single case of graft loss. Vascular surgical repair succeeded in 130 to 180 patients, but graft loss occurred in 20 cases and recurrent stenosis in 11. Mortality was reported in five cases. Our review of the literature and experience suggests that PTA may be preferred in the treatment of RTAS.

Adult↗

Effective use of streptokinase for peritoneal catheter failure.

The fibrinolytic enzyme streptokinase (streptase) was infused into the peritoneal catheter in 19 episodes of catheter failure in 16 patients. Intraabdominal bleeding prior to infusion was seen in seven of these episodes. Fibrin strands and clots were present in four additional successful cases. Streptokinase successfully relieved the obstruction in 13 episodes in 11 patients. The procedure failed in two cases of omental ingrowth and in another with catheter malposition. Streptokinase infusion also failed in two patients with Pseudomonas aeruginosa and one patient with Staphylococcus epidermidis peritonitis. Intraperitoneal streptokinase infusion is simple and free of side effects. Its use should be considered in peritoneal catheter failure, particularly in cases where bleeding or fibrin accumulation may play a role.

Adult↗

Legionnaires' disease associated with rash and renal failure.

Legionnaires' disease is recognized as a multisystemic illness. Afflicted patients may have pulmonary, gastrointestinal tract, and central nervous system complications. However, dermal involvement is not well documented and renal insufficiency is uncommon and usually of mild severity. We report two consecutive cases of proven Legionella infection that were unusual in that a macular rash and profound renal failure requiring hemodialysis were noted. Skin biopsy specimens of the rash and autopsy findings suggest that these atypical features may have been mediated by the Legionella infection. Although it is not entirely clear from these two cases, we suggest that the skin and renal involvement may have been mediated by either a "toxin" elaborated by the organism, an immunologic response of the host to the organism, or some other unidentified mechanism.

Acute Kidney Injury↗