[Future perspective for diabetics with nephropathy: not always cause for pessimism].
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Adult↗
Biomedical subjects
A J Donker
Publications and source records attributed to A J Donker.
Urinary albumin excretion, cardiovascular disease, and endothelial dysfunction in non-insulin-dependent diabetes mellitus.
Raised urinary albumin excretion (UAE) is associated with an increased risk of cardiovascular disease in non-insulin-dependent diabetes mellitus (NIDDM). We have examined the role of endothelial dysfunction as a possible explanation for this association in 94 NIDDM patients by investigating UAE, new cardiovascular events, and plasma concentration of von Willebrand factor (vWF), an indicator of endothelial dysfunction. At baseline, 66 patients had normal UAE (less than 15 micrograms/min), which remained normal in 33 (group 1) and increased in 33 (to median 31.5 micrograms/min, group 2). In 28 patients, baseline UAE was abnormal (67.1 micrograms/min, group 3). Follow-up ranged between 9 and 53 months. vWF did not change in group 1 (median 128% at baseline and 123% at follow-up), but increased in group 2 (from 116 to 219%, p less than 0.0001) and group 3 (from 157 to 207%, p = 0.0005). Baseline level of and change in vWF were strongly related to the development of microalbuminuria (R2 = 0.60, p less than 0.0001), but cardiovascular risk factors were not (R2 = 0.14). Raised baseline UAE was associated with an increased risk of new cardiovascular events only in patients with vWF concentrations above the median (relative risk 3.66, 95% CI 1.3-11.9) and not in patients with lower vWF (0.19, 0.01-1.33). In addition, the cardiovascular risk associated with increased UAE was modified by low compared with high concentrations of serum high density lipoprotein cholesterol (2.86 [1.03-8.48] vs 0.15 [0.01-1.43]). Dysfunction of vascular endothelium may be a link between albuminuria and atherosclerotic cardiovascular disease in NIDDM.
Adult↗
Autoantibodies against constituents of neutrophils in the diagnosis and treatment of (isolated) subglottic stenosis.
Six patients had a subglottic stenosis either as a presenting symptom or as a manifestation of a systemic disease. All patients had in common the presence of circulating autoantibodies against constituents of neutrophils on indirect immunofluorescence. Cytoplasmic and perinuclear staining patterns were recognized. Such autoantibodies have been reported in Wegener's granulomatosis, microscopic polyarteritis, (idiopathic) glomerulonephritis, and Churg-Strauss syndrome. However, only one of the six patients fulfilled the criteria for these conditions. Because a positive test for autoantibodies against constituents of neutrophils is rare in other conditions and because other diseases had been excluded, we suggest that this places subglottic stenosis within the spectrum of necrotizing (granulomatous) vasculitis. The consequences for therapy are discussed.
Adolescent↗
von Willebrand factor and early diabetic retinopathy: no evidence for a relationship in patients with type 1 (insulin-dependent) diabetes mellitus and normal urinary albumin excretion.
High plasma levels of von Willebrand factor, an indicator of endothelial cell dysfunction, have been reported in both diabetic retinopathy and nephropathy. It is unclear, however, whether von Willebrand factor is related to diabetic retinopathy in the absence of diabetic nephropathy. The relationship between retinal status and plasma von Willebrand factor concentration was investigated in a cohort of 17 patients with Type 1 (insulin-dependent) diabetes mellitus who were followed-up for a median of 42 months. The patients were examined three times. They were selected for having had normal urinary albumin excretion and no evidence of retinopathy (on fundoscopy) at the first and second examination. They were then divided into two groups, according to absence (Group A; n = 9) or presence (Group B; n = 8) of retinopathy on fundoscopy or fluorescein angiography at the third examination. Urinary albumin excretion remained normal in all patients. Plasma von Willebrand factor levels were similar in both groups: (median) 128 vs 123%, 164 vs 132% and 159 vs 130% (first, second and third examination, respectively). Median changes in plasma von Willebrand factor were also similar: +7 vs +9% and +5 vs +1% (first-second and second-third examination). Patients in whom the plasma von Willebrand factor concentration increased had higher systolic blood pressure at the third examination (150 +/- 30 vs 130 +/- 12 mmHg, p = 0.02) when compared to those in whom plasma von Willebrand factor did not increase, but were of similar age and had similar diabetes duration, retinal status, diastolic blood pressure, glycated haemoglobin and serum cholesterol concentration.(ABSTRACT TRUNCATED AT 250 WORDS)
Aged↗
Efficacy of low-dose captopril in addition to furosemide and spironolactone in patients with decompensated liver disease during blunted diuresis.
The renin-angiotensin-aldosterone system is activated by diuretics and involved in the diuretic resistance of cirrhotic patients with ascites and oedema. In previous studies relatively high doses of captopril (25-400 mg daily) were unsuccessful in promoting diuresis and natriuresis in these patients. We analyzed the efficacy of a low dose of captopril in eight patients with massive ascites resistant to therapy of salt/fluid restriction and increasing doses of spironolactone and furosemide. Mean duration of diuretic use was 73 days (range 7-240 days). After at least 3 days of observation on 80 mg furosemide and 100 mg spironolactone only, captopril was added. Four out of eight patients responded with an increase in natriuresis and diuresis; daily dose of captopril was 20.6 mg in responders and 26.5 mg in non-responders. After the addition of captopril the mean weight change was -7.5 kg in responders and +0.25 kg in non-responders. Mean urinary sodium output in responders increased from 72.8 (S.D. = 35.2) to 128.5 (63.5) mmol within 10 days. Increased diuresis in responders made diuretic reduction necessary: mean furosemide from 80 to 53.3 mg, and mean spironolactone from 100 to 68.1 mg. Creatinine clearances remained stable. High levels of plasma renin activity, plasma aldosterone and angiotensin-II were found in all patients. Non-responders showed more severe hyponatremia and higher vasopressin levels. Natriuretic atrial factor (NAF) was in the upper-normal range or slightly elevated in both groups. In non-responders we noticed low levels of cGMP in 24-h urine, compared with responders.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Peritoneal defense in continuous ambulatory versus continuous cyclic peritoneal dialysis.
Several centers have reported a lower rate of peritonitis among adult patients on continuous cyclic peritoneal dialysis (CCPD) as compared to those undergoing continuous ambulatory peritoneal dialysis (CAPD). Preliminary results of our ongoing prospective randomized study comparing CAPD-Y with CCPD also suggest a lower peritonitis incidence among CCPD-treated patients. To investigate whether the two dialysis regimens could result in differences in local host defense, we studied peritoneal macrophage (PMO) function and effluent opsonic activity in eight patients established on CAPD-Y matched with eight chronic CCPD patients. Since short and long dwell times are inherent to both dialysis modalities, and we previously found that dwell time has an impact on PMO function and effluent opsonic activity, patients were studied after both a short (4 hr) and a long (15 hr) dwell time. In both groups PMO phagocytic capacity increased significantly with dwell time (39 +/- 3.3% at 4 hr vs. 58 +/- 4.2% at 15 hr in CAPD patients, and 40 +/- 3.9 vs. 72 +/- 3.3% in CCPD patients; P less than 0.01), as did PMO peak chemiluminescence response (31 +/- 4.9 vs. 77 +/- 7.2 counts.min-1/10(4) cells in CAPD, and 22 +/- 3.9 vs. 109 +/- 21.2 counts.min-1/10(4) cells in CCPD; P less than 0.01) and effluent opsonic activity (41 +/- 7.6 vs. 73 +/- 5.8% in CAPD and 39 +/- 6.2 vs. 70 +/- 5.9% in CCPD; P less than 0.01). However, no significant difference was found in either variable between CAPD and CCPD patients when dwell times were equal.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Assessment of post-dialysis dry weight: an application of the conductivity measurement method.
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Adult↗
Acute hyperinsulinemia induces sodium retention and a blood pressure decline in diabetes mellitus.
Hyperinsulinemia supposedly contributes to hypertension in diabetes mellitus. We sought to determine if the renal and cardiovascular effects of insulin are preserved in diabetes despite resistance to its glucose-lowering effect. We studied the effects of two doses of insulin (50 and 500 milliunits/kg.hr-1), using the euglycemic clamp technique, on fractional sodium excretion, blood pressure, and heart rate in two groups of non-insulin-dependent diabetics: eight patients with and eight patients without hypertension. Hypertensive diabetics had higher basal insulin levels than normotensive diabetics (21.8 +/- 2.9 and 14.4 +/- 1.6 milliunits/l, respectively [mean +/- SEM]; p = 0.03). The degree of insulin resistance, but not plasma insulin levels, correlated with the height of mean arterial blood pressure (r = 0.60 and 0.73 at the low and high insulin dose, respectively; p less than 0.05). In contrast, the change in mean arterial blood pressure correlated negatively with the change in endogenous insulin levels during the control experiment (r = -0.41, p less than 0.02). Exogenous insulin induced a similar reduction in fractional sodium excretion in normotensive and hypertensive diabetics (43 +/- 5.9% and 48 +/- 16.4% during the low insulin dose and 57 +/- 9.1% and 62 +/- 12.5% during the high insulin dose, respectively). A decline in blood pressure was noted that correlated with the whole body glucose uptake during the high insulin dose (r = 0.52, p less than 0.05). Since heart rate response and plasma norepinephrine level during the insulin clamp were comparable in both groups, an abnormality of the baroreceptor reflex is suggested. It appears that insulin resistance, but not insulin, is primarily related to hypertension. At the same time, insulin may still exert some effect on blood pressure by way of its renal or vasodilatory, or both, action.
Acute Disease↗
Pharmacokinetics of ciprofloxacin after intraperitoneal administration in uninfected patients undergoing CCPD.
Ciprofloxacin is increasingly used to treat peritoneal dialysis related peritonitis. We studied the pharmacokinetics of intraperitoneally administered ciprofloxacin in six uninfected CCPD patients. In a randomized cross-over setting ciprofloxacin was added either to a long dwell exchange (lastbag) or to four short dwell exchanges (dwell time 1.5 h). Addition of ciprofloxacin (25 mg/l) during the four short dwell exchanges resulted in dialysate levels of 21.1-13.3 mg/l during these exchanges. In the subsequent last bag devoid of ciprofloxacin a dialysate Cmax,D of 1.38 mg/l was observed at 30 min. Mean +/- SD serum Cmax,S was 0.59 +/- 0.29 mg/l after 5.4 h. Instillation of 100 mg/l ciprofloxacin in the last-bag yielded Cmax,D of 99.1 mg/l, falling with a t1/2 of 3.3 h towards levels < 2 mg/l at 19.8 h. A mean +/- SD serum Cmax,S of 0.69 +/- 0.19 was reached after 4 h. During four subsequent 1.5h exchanges without ciprofloxacin dialysate levels were < 0.1 mg/l. Instillation of 25 mg/l ciprofloxacin in the last-bag yielded a Cmax,D of 21.7 mg/l, falling towards levels < 2 mg/l at 15 h with a t1/2 of 3.85 h. A mean +/- SD serum Cmax,S of 0.26 +/- 0.03 was reached after 8 h. We conclude that the rapid absorption of ciprofloxacin from the dialysate into the tissues requires ciprofloxacin to be administered to all CCPD bags to ensure bactericidal dialysate levels. When therapeutic serum levels are required higher intraperitoneal doses or an oral or i.v. loading dose is warranted.
Adult↗
Clinical strategies for arresting progression of renal disease.
The incidence of end-stage renal disease is increasing and this results in an enhanced requirement of renal replacement therapy facilities. This brings about a significant burden on health care budgets and makes strategies that slow down or even prevent deterioration of the renal function mandatory. Although large scale randomized, controlled and prospective clinical trials on the effect of blood pressure control on the course of renal function are lacking, there is circumstantial evidence from animal, epidemiological and clinical studies to state that treatment of hypertension to blood pressure values well within the normal range is most important to ameliorate the downhill course of renal function in patients with chronic renal failure. Moreover, treatment of hypertension is critical to reduce morbidity and mortality of cardiovascular disease in these patients, who have an increased risk for such events. Low-protein diets, if possible with ketoacid supplement, are advocated to slow down the deterioration of renal function. However, based on the results of recent studies, low-protein diets may only have a moderate effect in patients with diabetic nephropathy and, possibly, in patients with chronic glomerulonephritis. The possibility of influencing renal ammoniagenesis by protein restriction or calcium carbonate administration, and an attenuation of alternative complement pathway activation and tubulo-interstitial injury, are challenging. Finally, in animal studies it has been found that abnormalities in serum lipid profile contribute to the progression of chronic renal failure, which may be prevented by pharmacological treatment of hyperlipidemia. Studies in humans concerning this subject are lacking at this moment, but treatment of hyperlipidemia is proper to reduce cardiovascular events.
Ammonia↗
The effects of dietary supplementation with fish oil on renal function and the course of early postoperative rejection episodes in cyclosporine-treated renal transplant recipients.
In a randomized prospective coconut oil (daily 6g[63% C8:0 and 36% C10:0] [EPA-] [n = 48])-controlled trial, we investigated the effect of a one-month dietary supplementation with daily 6 g fish oil (30% C20:5 omega-3 and 20% C22:6 omega-3 as their methyl esthers [EPA+] [n = 40]) on the incidence and course of early postoperative rejection in 88 first cadaveric, cyclosporine-treated renal transplant recipients. At one month there were no differences in renal function and incidence of rejection episodes. When analyzed separately for rejection (re+) or nonrejection (re-), the rejecting and fish oil-treated patients showed a significant better recovery of renal function after a histologically confirmed rejection episode, creatinine clearance being 43 ml/min/1.73m2 in the EPA+re+group versus 27 ml/min/1.73 m2 in the EPA-re+group (P less than 0.05), and serum creatinine being 183 and 283 mumol/l (P less than 0.05), respectively. The prerejection renal function and the decline of renal function during the rejection episode did not differ significantly between the EPA+re+ and the EPA-re+ groups. The nonrejecting fish oil-treated patients showed no better renal function than the nonrejecting coconut oil-treated patients. However, cyclosporine trough levels were significantly higher in the fish oil-treated group (EPA+re- 251 versus EPA-re- 200 ng/ml [P less than 0.05]). From these results we conclude that dietary supplements with fish oil favorably influence renal function in the recovery phase following a rejection episode in cyclosporine-treated renal transplant recipients. We further conclude that one month after grafting there is no difference in the incidence of rejection episodes between the fish- and coconut oil-treated patients. The same holds true for renal function in the absence of rejection, and for the decline in renal function during a rejection episode.
Creatinine↗
The recovery of the fluid balance after hemodialysis and hemofiltration.
Dialysis dysequilibrium syndrome is a frequent complication of renal replacement therapy and seems to be related to changes in fluid balance. From previous studies it is known that these changes are less pronounced during hemofiltration (HF), leading to a lower incidence of complaints compared to hemodialysis (HD). To assess the severity and duration of the dysequilibrium syndrome, intracellular (ICV) and extracellular fluid volumes (ECV) were measured during and after HD and HF by means of a non-invasive conductivity method. Blood volume changes were calculated from pre- and post-treatment erythrocyte counts. Seven HD and eight HF patients were studied. Ultrafiltration volume did not differ between both groups. Blood volume decrease was less during HF due to a significant decrease in ICV, the latter being in contrast to an ICV increment during HD. The significant decrease in ICV led to a less severe decrease in ECV (90 versus 85%). Overall, this resulted in a better vascular refill during HF. At the end of treatment ICV and ECV were not in equilibrium yet. During the recovery period ICV increased roughly 3% in the HF group. In the HD group some patients showed an increase while others showed a decrease in ICV. Overall, no change in ICV was noticed. During recovery ECV decreased further in both groups. The measured recovery period was significantly shorter after HF (245 +/- 68 min) than after HD (299 +/- 37), supporting the hypothesis that HF is a more physiological way of treatment compared to HD.
Aged↗
Influence of high and low sodium dialysis on blood volume preservation.
Haemodialysis has a profound effect on fluid balance. Since fluid is initially withdrawn from the intravascular compartment, hypovolaemia is a frequent complication. A fluid shift from the overhydrated interstitium towards the intravascular compartment can counteract hypovolaemia. However, a fast decline in extracellular osmolality may cause an increase in the intracellular volume, reducing the available amount of fluid to compensate for the hypovolaemia. To overcome this problem, the use of alternating high and low sodium dialysate is advocated. In this study six patients were studied during standard haemodialysis (HD) and during dialysis with alternating high and low sodium dialysate (HLSD). Changes in intracellular fluid volume (IFV) and extracellular fluid volume (EFV) of tissue and blood were measured by means of a non-invasive electrical conductivity method. Changes in blood volume (BV) were studied by serial erythrocyte counts. Plasma sodium concentration was determined at regular intervals. The distribution volume of sodium during the high and low sodium episodes of HLSD was calculated according to a mathematical model. HLSD led to fluctations in plasma sodium concentration that induced changes in red cell volume, but not in IFV. Distribution of sodium was largely confined to blood. BV was better preserved during HLSD than during HD, probably due to a higher mean plasma sodium concentration. Postdialysis sodium concentration however, was not significantly different between HLSD and HD. These data suggest that the better BV preservation during HLSD results from an induced osmotic gradient across the capillary wall, rather than from an osmotic gradient across the cell membrane.
Blood Volume↗
The effect of angiotensin-I converting enzyme inhibition on insulin action in healthy volunteers.
Acute hyperinsulinaemia, achieving insulin levels within the physiological range, induces sodium retention. At the same time an activation of the renin-angiotensin system occurs, with a rise in plasma renin activity (PRA) and angiotensin-II level but no change in plasma aldosterone. After administration of higher, pharmacological doses of insulin an increase in systolic blood pressure and heart rate can also be observed, while further increases in PRA and angiotensin-II are noted. To determine whether angiotensin-II is involved in observed insulin actions, we studied the renal and cardiovascular effects of three dosages of insulin (50 (Ins I), 300 (Ins II) and 500 (Ins III) mU kg-1 h-1) in healthy subjects after one week of treatment with the angiotensin-I converting enzyme inhibitor enalapril (10 mg twice a day), using the euglycaemic clamp technique. Control data were obtained from two previously conducted experiments in the same subjects, one with infusion of insulin and one with the insulin solvent only. The effect of insulin on fractional sodium excretion, blood pressure and heart rate was unaffected by enalapril, which precludes any involvement of the renin-angiotensin system with regard to these aspects of insulin action. Insulin sensitivity increased significantly during treatment with enalapril (with enalapril: Ins I: 11.3 +/- 3.0, Ins II: 20.0 +/- 3.4 and Ins III: 20.6 +/- 3.9 mg kg-1 min-1 glucose (mean +/- SD); without enalapril: Ins I: 8.7 +/- 2.3, Ins II: 13.7 +/- 3.0 and Ins III: 15.5 +/- 3.1 mg kg-1 min-1 glucose; P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Another reason to restrict the use of a hypertonic, glucose-based peritoneal dialysis fluid: its impact on peritoneal macrophage function in vivo.
Previous in vitro studies have revealed that the currently used peritoneal dialysis fluids (PDFs) inhibit several functions of phagocytic cells. Glucose-mediated hypertonicity was demonstrated to be one of the major detrimental factors. To investigate the clinical relevance of these in vitro findings, we compared the in vivo effect of a PDF with 3.86% glucose (D386) and a PDF containing 1.36% of glucose (D136) on peritoneal macrophage (PMO) function in eight CCPD patients. In a randomized cross-over setting, each patient used exclusively D136 or D386 on day one. The next day the patients who used D136 were switched to D386 and vice versa. PMO were isolated from the effluents and studied for their phagocytic capacity and chemiluminescence response. PMOs obtained from D386 effluents were significantly less phagocytic as compared to PMOs obtained after the in vivo use of D136 (38 +/- 7.1 vs 63 +/- 8.3%, p less than 0.02). In addition PMOs exposed to D386 were less able to mount a respiratory burst (peak response 4 +/- 1.0 vs 15 +/- 1.4% of control cells, p less than 0.05). Thus, the in vivo use of D386 was accompanied by significantly decreased PMO functions. These findings further stress the need to search for alternative solutions that do not rely on glucose-mediated hypertonicity for ultrafiltration.
Adult↗
The effect of glycerol-containing peritoneal dialysis fluid on peritoneal macrophage function in vivo.
Though glucose is universally applied as osmotic agent in CAPD, there is great interest in the use of alternative osmotic agents. Glycerol-containing peritoneal dialysis fluids (G-PDF) have been used in an attempt to minimize the metabolic effects of long-term exposure to glucose, especially in patients with diabetes. Since data were lacking, we studied the effect of G-PDF on peritoneal macrophage (PMO) function. In a randomized cross-over setting eight stable diabetic CAPD patients performed the third and fourth exchange of the day with either G-PDF or with glucose-containing PDF (D-PDF) of comparable osmolality. The next day the patients who had used G-PDF were switched to D-PDF and vice versa. PMO were isolated from the effluents and tested for their phagocytic capacity and chemiluminescence response. No differences were encountered in total and differential white cell counts between G-PDF and D-PDF effluents. PMO phagocytic capacity for both S. epidermidis (SE) and E. coli (EC) was significantly depressed after the instillation of G-PDF as compared to D-PDF (SE: 52 +/- 2.7 vs 69 +/- 5.0%, p less than 0.02, and EC: 44 +/- 5.7 vs 63 +/- 6.7%, p less than 0.02). The same held true for peak chemiluminescence response (5.3 +/- 1.36 vs 7.2 +/- 1.43% of control cells, p less than 0.005). Thus, G-PDF may compromise PMO function in vivo more than D-PDF despite its more favourable metabolic profile as compared to D-PDF for diabetic patients.
Adult↗
A prospective, randomized study comparing the peritonitis incidence of CAPD and Y-connector (CAPD-Y) with continuous cyclic peritoneal dialysis (CCPD).
Both CAPD-Y and CCPD have been reported to reduce the high peritonitis rate of conventional CAPD. As peritonitis was the major complication of CAPD in our centre, both modifications were introduced in 1987. Initially, treatment modalities were allocated to patients based on their (doctor's) preference. A remarkable difference in peritonitis rate was encountered between patients on CCPD and those on CAPD-Y (0.6 vs 1.2 episodes a year). As patient selection and doctor's preference might have contributed to this hopeful result, a prospective study was started. From January 1988 on, all new patients were at random assigned to CAPD-Y or CCPD in order to study the incidence of peritonitis in relation to the treatment modality. Up till November 1, 1990, 26 patients enrolled in the CAPD-Y group (follow-up of 292 patient months), and 30 patients in the CCPD group (follow-up of 337 patient months). This ongoing study reveals that CCPD patients remained peritonitis free significantly longer than those on CAPD-Y (quartile time to first peritonitis greater than 12 vs 3 months, p less than 0.05), and had a significantly lower peritonitis incidence (median time to second peritonitis 18 vs 6 months, p = 0.016). In conclusion, in an unselected patient population CCPD was accompanied with a significant lower peritonitis incidence than CAPD-Y.
Adult↗
Renal function and metabolism during endotoxemia in rats: role of hypoperfusion.
Renal failure often complicates endotoxin shock. This might be due to renal hypoperfusion, but endotoxemia could also have additional effects. We studied in anesthetized rats renal plasma flow (RPF), glomerular filtration rate (GFR), and metabolism (ATP, CrP = creatine phosphate, energy charge = [ATP + 0.5 ADP]/[ATP + ADP + AMP], lactate, glucose) during endotoxin shock (Escherichia coli endotoxin, 10 mg/kg for 60 min; n = 10) and "balloon shock" (balloon inflated in vena cava below renal vein to cause comparable decreases in cardiac output and RPF as in endotoxin-treated rats; n = 10). A third group of rats served as controls (n = 10). At t = 0 infusion of endotoxin was started. At t = 90 min, when cardiac output was low and serum lactate was high (indicating shock), GFR and RPF were obtained from plasma disappearance rates (from t = 90 to t = 135 min) of 125I-thalamate and 131I-hippurate, respectively. Experiments ended at t = 135 min. In both shock groups RPF decreased (by ca. - 75% compared with control rats), but filtration fraction only increased (by 72%) in the "balloon shock" rats. In renal biopsies lactate concentration increased more (by 407 vs. 167%) and ATP decreased more (by -63 vs. - 35%) during endotoxin shock than during "balloon shock"; the endotoxin-treated rats also showed a significant decrease in CrP (by - 58%), energy charge (by - 31%), and glucose concentration (by - 34%), and an increase in the number of leukocytes in the glomeruli (by 730%). Renal function and metabolism thus was more affected in this hypodynamic form of endotoxin shock than in "balloon shock." This may be caused by the effects of endotoxin on sticking of leukocytes and renal metabolism.
Adenosine Diphosphate↗