Margaret L. MacDougall

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.

Effect of Angiotensin-Converting Enzyme Inhibition on Renal Function and Albuminuria in Normotensive Type I Diabetic Patients

Normotensive patients with insulin-dependent (type l) diabetes mellitus (n = 18) were given 25 mg captopril (b.i.d.) and placebo for 3 mo in a randomized double-blind crossover study. Patients had normal renal function, and none had retinopathy. Albuminuria was <20 μg/min in 12 patients and between 20 and 200 μg/min in the other 6. Patients were examined at the end of the placebo and captopril phases. Captopril caused little reduction in blood pressure obtainedby 24-h ambulatory monitoring (systolic 126.0 ± 2.7 to 123.9 ± 2.4 mmHg, P< 0.08; diastolic 74.2 ± 1.9 to 72.1 ± 1.9 mmHg, P < 0.09). Captopril lowered glomerular filtration rate from 99.5 ± 7.7 to 71.0 ± 5.5 ml · min−1 · 1.73 m−2(P < 0.01), whereas renal plasma flow (443.9 ± 15.2 ml.min−1. 1.73 m−2) remained unchanged. Filtration fraction was reduced from 22.4 ± 1.4 to 17.4 ± 1.4% (P < 0.01). Urinary albumin excretion was reduced from 59.1 ± 0.15 to 27.7 ± 13.9 μg/min (P < 0.1). Reduction was relatedto the extent of initial albuminuria (r = 0.997, P < 0.001), a relationship that remained significant after logarithmic transformation (r = 0.540, P < 0.02). Dextran clearance was used to determine glomerular capillary function. Angiotensin inhibition caused reduction in effective glomerular pore size and also reduced flow via the nondiscriminatory shunt. Angiotensin inhibition in normotensive patients with type I diabetes was well tolerated. Reduction in albuminuria is mediated by a combination of hemodynamic changes and alterations in glomerular capillary function.

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.

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.

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.

Effects of Misoprostol on Contrast-Induced Renal Dysfunction.

Radiographic contrast-induced nephropathy (RCIN), defined by a variable rise in serum creatinine, occurs in up to 40% of contrast radiologic procedures. A prospective, randomized double-blind study was done to determine whether misoprostol prevented or modified RCIN. Patients with a serum creatinine less-than-or-equal2.0 mg dl(minus sign1), who were scheduled to undergo a radiologic contrast procedure (N = 125), were randomized to receive placebo (N = 62) or misoprostol (N = 63) given at 200 &mgr;g Q.I.D. for 72 h prior to contrast and for 48 h after contrast. Contrast significantly decreased creatinine clearance, and misoprostol significantly diminished the dysfunction. The effect was more pronounced in patients with diabetes mellitus (N = 24) and patients on nonsteroidal anti-inflammatory drugs (NSAIDs) (N = 47). Our findings are consistent with a functional role of prostaglandins in the renal response to contrast. We conclude that short-term administration of misoprostol is a useful adjunct for contrast procedures, especially in patients with diabetes and patients on NSAIDs.

Controlled Changes in Chronic Dietary Protein Intake Do Not Change Glomerular Filtration Rate

The effect on renal function (creatinine clearance [Ccreat] and inulin clearance [Cinulin]) of changes in chronic dietary protein intake was studied in seven healthy male subjects. Serial 24-hour urine collections were used to determine creatinine excretion (UcreatV) and Ccreat. Subjects were examined after ad libitum (ad lib) food intake and after 2-week periods of high protein diet ([HPD] 1.6 g/kg body weight [BW] per day) and low protein diet ([LPD] 0.5 g/kg BW per day). Inulin clearance (Cinulin) was determined at the end of each 2-week diet period. UcreatV increased from 1,838.8 +/- 97.2 mumol/kg (20.8 +/- 1.1 mg/kg) BW to 2,068.6 +/- 106.1 mumol/kg (23.4 +/- 1.2 mg/kg) BW daily during HPD and decreased significantly to 1,555.9 +/- 167.9 mumol/kg BW per day (17.6 +/- 1.9 mg/kg BW per day) with beginning of LPD. Ccreat rose from 1.54 +/- 0.09 mL/s 1.73 m2 (92.5 +/- 5.5 mL/s.1.73 m2 (104.7 +/- 4.9 mL/min/1.73 m2) during HPD and decreased to 1.23 +/- 0.04 mL/s.1.73 m2 (74.0 +/- 2.2 mL/min/1.73 m2) with initiation of LPD. There was no difference between Cinulin after HPD (1.42 +/- 0.12 mL/s.1.73 m2; 84.9 +/- 7.2 mL/min/1.73 m2) and after LPD (1.36 +/- 0.05 mL/s.1.73 m2; 81.4 +/- 2.9 mL/min/1.73 m2). This study confirms the effect of protein intake on Ccreat and UcreatV, but fails to show an effect of changes in chronic protein intake on glomerular filtration rate (GFR). Ccreat during dietary protein restriction to 0.5 g/kg/d is similar to Cinulin and may be a useful measure of GFR under circumstances where more specific inulin or isotope studies are not available.

Evidence that inhibition of hepatic drug oxidation by tumors is mediated by a circulating humor.

Summary Transplantation of a nonme-tastasizing fibrosarcoma into one member of a parabiotic pair of rats produced inhibition of hepatic microsomal drug oxidation in both members. This observation is considered evidence that this tumor secretes a circulating substance which inhibits hepatic drug metabolism.

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.

The effect of water loading on albumin excretion in Type I diabetes mellitus

An increased albumin excretion rate is recognized as an important early marker for incipient kidney disease in patients with diabetes mellitus. Many different techniques have been used, and a single void technique has been proposed as the simplest method for screening for increased albumin excretion. We evaluated a previous observation that single void samples during water diuresis yield increased albumin excretion rates. Timed day, night, and 24 hour albumin excretion rates (AER) were obtained in 35 patients with Type I diabetes mellitus. This was followed by examination of 8 consecutive half-hour specimens obtained during continued water diuresis. We compared 26 patients with low AER (less than 20 micrograms/min/24 hr sample) to 9 patients with high AER (greater than 20 and less than 200 micrograms/min/24 hr). Sampling began 60 min after the initiation of the waterload. At first, the AER in the low AER group was significantly higher than it was at night, but it decreased over 60 to 90 min of sampling to levels comparable with daytime AER. This was paralleled by a similar pattern in urine flow rate, sodium, and solute excretion. The AER in the high AER group did not increase with the water load and remained high throughout the study periods. The pattern of urine flow rate, sodium, and solute excretion was similar to that of the group with low AER. The study demonstrates that early sampling after water-induced diuresis leads to overestimation of AER in patients with low AER as compared to patients with high AER.(ABSTRACT TRUNCATED AT 250 WORDS)