The role of disease duration and hypertension in albumin excretion of type I diabetes mellitus.

The objective of this study was to examine the relationship between blood pressure, albumin excretion, and renal function in patients with type I diabetes mellitus. The study design was as follows: nonselected consecutive patients with type I diabetes mellitus were divided into three groups by level of albumin excretion rate (AER): less than 20 micrograms/min, 20 to 200 micrograms/min, and greater than 200 micrograms/min. The setting for the study was an outpatient diabetic clinic in a tertiary referral center. There were 166 patients studied: 53% men, 47% women, 86% white, 17% treated for hypertension. Seventy-six percent had an AER less than 20 micrograms/min, 18% had an AER of 20 to 200 micrograms/min, and 6% had an AER of greater than 200 micrograms/min. Glycosylated hemoglobin did not differ between groups. AER was increased with age and disease duration (P less than 0.005 by analysis of variance) after 10 yr of disease. Serum creatinine (P less than 0.005) and systolic (P less than 0.005) and diastolic (P less than 0.01) blood pressures were also increased with AER. Serum creatinine and blood pressure were found to be increased in parallel after 10 yr of disease, but both remained within the normal range overall. A comparison of individual blood pressures in patients not taking antihypertensive drugs (N = 138) with age-related blood pressures of nondiabetic subjects revealed increased systolic and diastolic blood pressures at all ages. Group comparison demonstrated a significant link between increased AER and serum creatinine (declining renal function) and increased blood pressure after a latent period of 10 yr. Blood pressure appears to be increased from the earliest age in diabetes compared with healthy populations.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of angiotensin-converting enzyme inhibition on renal function and albuminuria in normotensive type I diabetic patients.

Normotensive patients with insulin-dependent (type I) 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 less than 20 micrograms/min in 12 patients and between 20 and 200 micrograms/min in the other 6. Patients were examined at the end of the placebo and captopril phases. Captopril caused little reduction in blood pressure obtained by 24-h ambulatory monitoring (systolic 126.0 +/- 2.7 to 123.9 +/- 2.4 mmHg, P less than 0.08; diastolic 74.2 +/- 1.9 to 72.1 +/- 1.9 mmHg, P less than 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 less than 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 less than 0.01). Urinary albumin excretion was reduced from 59.1 +/- 0.15 to 27.7 +/- 13.9 micrograms/min (P less than 0.1). Reduction was related to the extent of initial albuminuria (r = 0.997, P less than 0.001), a relationship that remained significant after logarithmic transformation (r = 0.540, P less than 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.

Single-dose subcutaneous iodine-131-iodohippurate for determination of renal plasma flow.

Subcutaneous administration of a single dose of 131I-iodohippurate was used for determination of renal plasma flow (RPF) in 20 subjects during water diuresis. Slow release of tracer (200 microCi) permitted serial clearance measurements over 5 hr that were compared to standard, constant infusion, PAH clearance (mean 379.5 +/- 34.9 ml/min/1.73 m2, range 50.9 to 696.3 ml/min/1.73 m2). RPF(Isotope) was 424.9 +/- 30.3 ml/min/1.73 m2 (range 144.4 to 746.5 ml/min/1.73 m2) and highly correlated with RPFPAH (r = 0.883, p less than 0.0001). This technique permits prolonged studies of renal plasma flow under steady-state conditions without constant infusion.

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.

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.

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.

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.

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.

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.

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)

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.

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.

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.

Spontaneous subcapsular and perinephric hemorrhage in end-stage kidney disease: clinical and CT findings.

Clinical, CT, and pathologic findings were analyzed in six patients with spontaneous subcapsular or perinephric hematomas complicating end-stage kidney disease. Renal failure had been managed by hemodialysis in four patients, by renal transplantation in one, and by conservative methods in one. All patients had nonspecific abdominal pain. CT clearly showed in all cases that the pain resulted from hemorrhage and also revealed the extent and location of hematomas. In addition, in four patients, CT showed underlying acquired cystic kidney disease that was the probable cause of hemorrhage. In one of these patients, CT also showed a renal cell carcinoma in the opposite kidney. Other causes for renal hemorrhage encountered in the series included renal infarction due to small vessel disease, heparinization during hemodialysis, and thrombocytopenia. Abdominal CT is a useful technique for evaluating patients with end-stage renal disease who have abdominal pain or who exhibit clinical evidence of blood loss.

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.

Arachnoid cyst in a patient with autosomal-dominant polycystic kidney disease.

We report a case of an arachnoid cyst of the posterior cerebral fossa in a man with autosomal-dominant polycystic kidney disease. No traumatic or infectious etiology for the cyst could be identified.

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.

Thrombotic arm edema as a complication of subclavian vein catheterization and arteriovenous fistula formation for hemodialysis.

We report a case of persistent tense edema of the upper extremity following the surgical creation of an arteriovenous fistula for hemodialysis access. This was the result of poor venous return secondary to thrombosis of the subclavian vein. The thrombosis occurred after previous subclavian vein cannulation for hemodialysis.