G. Schultze

The influence of long-term infusion of the calcium antagonist diltiazem on postischemic acute renal failure in conscious dogs

SummaryThe influence of long-term infusion of the calcium-entry blocker diltiazem on postischemic acute renal failure was investigated in conscious dogs monitored by implanted instruments. In 18 uninephrectomized beagle dogs on a salt-rich diet, an electromagnetic flow probe and an inflatable plastic cuff were placed around the renal artery. Acute renal failure was induced by inflating the cuff for 180 min in the conscious animal. Group A (n=5, control) received an intraaortic injection of 0.9% NaCl (5 ml/day) from the 3rd day before until the 7th day after ischemia and group B (n=6, posttreatment) an intra-aortic injection of diltizem (5 µg·min−1·kg−1) beginning at the end of ischemia until the 7th day. Group C (n=7, pre- and posttreatment) received diltiazem from the 3rd day before until the 7th day after ischemia. In group A, renal blood flow dropped from 149±16 (preischemic) to 129±29 ml·min−1 on the 1st day after ischemia. In contrast, renal blood flow increased on the 1st postischemic day in both treatment groups by 29±15% (group B,P 0.05) and 14±13% (group C). In the following days, there was no significant difference in renal blood flow between groups A, B and C. In group B, the reduction of the glomerular filtration rate was similar to that in the control group. In group C, the glomerular filtration rate was significantly less reduced than in group A (34±1.8 preischemically to 17±5.4 on day 1,P 0.05 and 20±4.1 ml·min−1 on day 7,P 0.05). Plasma renin activity increased in both diltiazem groups, more pronounced so in group B (from 3.7±1.0 on day 1 to 16.2±7.9 ng ATI·ml−1·h−1 on day 7,P 0.05). In contrast to groups A and B, the increase in fractional sodium excretion was less pronounced in group C. Likewise, the decrease in free water-reabsorption was less marked than in groups A or B. It was apparent that diltiazem, when administered pre- and post-ischemically, preserved glomerular filtration rate and renal blood flow. When diltizem was given solely postischemically there was an improvement in renal blood flow, but no significant influence on glomerular filtration rate. We therefore conclude that mainly tubular factors, in addition to the attenuation of postischemic vasoconstriction, are involved in the protective effect of diltiazem on postischemic acute renal failure in conscious dogs.

Prostaglandin E2 Promotes Hypotension on Low-Sodium Hemodialysis

The influence of low-sodium dialysate (126 mmol/l) on plasma levels of prostaglandin E2 (PGE2) and PGF2 alpha, plasma renin activity (PRA) and arterial blood pressure was investigated in 16 patients on maintenance hemodialysis. PGE2 rose more than tenfold and there was a significant increase in PGF2 alpha and PRA. Mean arterial pressure dropped by 30 mm Hg causing discomfort in several patients. By contrast, conventional hemodialysis against 140 mmol/l of sodium was followed by less pronounced changes in plasma prostaglandins, and reduction of blood pressure was moderate (13 mm Hg). It is suggested that vasodilating prostaglandins may contribute to dialysis hypotension. Their origin may not be confined to the kidneys but rather extend to the lungs and circulating blood cells. The in vitro generation of prostaglandins was demonstrated when donor blood was circulated in an extracorporeal dialysis system.

Blood Pressure in Terminal Renal Failure

Most of the 52 patients on maintenance dialysis investigated in this study suffered from arterial hypertension in spite of efforts to reduce ‘dry weight’. In this situation we found that the majority

Membrane plasma exchange in Goodpasture's syndrome.

We report two cases with Goodpastures syndrome successfully treated by membrane plasma exchange. In both patients, pulmonary infiltrations and hemoptysis had already resolved after the first pulse methylprednisolone dose (1000 mg IV). Following plasma exchange, renal function did not further deteriorate in one patient and returned to normal in the other patient. From the clinical course of our patients and a review of the literature, we conclude that membrane plasma exchange is effective in preventing deterioration of renal function in Goodpastures syndrome. Analysis of the literature shows that patients who respond to plasma exchange have significantly fewer crescents and lower plasma creatinine, while non-responders are more often oliguric or anuric and require dialysis at the time of plasma exchange.

Elimination kinetics of plasma exchange

SummaryInterest in the therapeutic use of plasma exchange for various diseases is growing. The two different effects of plasma exchange are elimination and activation. The kinetics are linear for elimination by plasma exchange, but not for activation. Plasma exchange is performed intermittently and can be described by intermittent kinetics. According to intermittent kinetics, plasma exchange removes 50% to 75% of a substance in plasma within 1–2 h, corresponding to an elimination half-life of 30–40 min. Hybrid kinetics, a mixture of actually intermittent but theoretically continuous elimination by plasma exchange, can however also be applied. Hybrid kinetics are more convenient and more reliable than intermittent kinetics. This is because hybrid kinetics are based solely on the concentrations before each plasma exchange; hybrid kinetics also reflect removal from the entire body and not just from the plasma compartment. According to hybrid kinetics, the amount of a substance in the body removed within 3–4 days is 50% of the difference between the initial and the final plasma concentration, depending on the intensity of plasma exchange. The intensity may well contribute at least in part to the beneficial effect of plasma exchange in various diseases.

Gastrointestinal Protein Loss in the Nephrotic Syndrome Studied with 51Cr-Albumin

Gastrointestinal protein loss was studied by intravenous application of 51Cr-albumin and the measurement of fecal excretion of 51Cr. As compared to controls, fecal excretion of 51Cr was largely increased in 28 patients with nephrotic syndrome due to glomerular disease and in 11 patients with hypoproteinemia in the course of different gastrointestinal disorders. It was not increased in nephrotic patients without primary glomerular disease and in renal insufficiency without nephrotic syndrome. Controversial data of the literature are discussed with regard to different methods and patient groups.

Beneficial Effects of Long-Term Prostaglandin E2 Infusion on the Course of Postischemic Acute Renal Failure

The effect of a continuous intra-aortal infusion of prostaglandin E2 (PGE2) (0.03 microgram . min-1 . kg-1) on the course of postischemic renal failure (180 min cessation of blood flow by inflation of a pneumatic cuff) has been investigated in 11 conscious sodium-replete dogs. The glomerular filtration rate (51Cr-EDTA: endogenous creatinine clearance) was less decreased in the PGE2 group (group B, n = 6) than in the control group (group A, n = 5; 13 ml . min-1 vs. 22 ml . min-1; p less than 0.05). Renal blood flow (electromagnetic flow probe) was markedly lower in the control group (82 ml . min-1) than in the PGE2 group (130 ml . min-1; p less than 0.05), even exceeding baseline levels in the latter group. Accordingly, the excessive rise in renal vascular resistance in the control group (+277%) was abolished in the PGE2 group (-20%) (p less than 0.05). Nitrogen retention was also markedly improved. Plasma renin activity, which was markedly raised initially (25.8 ng angiotensin I . ml-1 . h-1) was not significantly further increased during the subsequent 7 days. Urinary excretion of PGE2 was diminished in the control group and elevated following PGE2 infusion. It is suggested that the beneficial effects of PGE2 are mediated by preservation of renal perfusion. Additional effects of prostanoids on the ultrafiltration coefficient (KF) and cytoprotection by reduction of intracellular calcium accumulation must also be taken into consideration.

Influence of Prostaglandin A1 on Renal Filtration, Hemodynamics and Excretion

The effect on renal function of a 210-min infusion of PGA1 into the aorta of 10 conscious beagle dogs has been investigated. In the sodium-replete group, PGA1 caused an increase in the glomerular filtration rate (GFR) (24%), renal blood flow (17%) and sodium excretion (20%). By contrast, in the sodium-depleted group, PGA1 caused a considerable reduction of GFR (25%) and sodium excretion (51%). In this group, baseline renal blood flow was lower, and there was no further reduction during PGA1 infusion. Fractional sodium excretion was unchanged in the sodium-replete dogs, but was reduced in the sodium-deplete state. Plasma renin activity was markedly elevated and further increased in the sodium-deplete group, but it was nearly unchanged in the sodium-replete group. This difference in renal response to exogenous PGA1 might be due to interaction with the renin-angiotensin system, which was markedly stimulated by sodium depletion and additionally by prostaglandin infusion.

Akutes Nierenversagen bei sekundärer renaler Oxalose

Bei einer 35jahrigen Patientin entwickelte sich nach der chirurgischen Behandlung eines Pankreasabszesses ein langsam progredientes akutes Nierenversagen. Wegen des untypischen Verlaufs wurde eine Nierenbiopsie vorgenommen; es fand sich eine schwere obstruktive renale Oxalose mit begleitender interstitieller Nephritis. Eine primare Oxalose wurde durch Bestimmung von Glycerat und Glycolat im Urin ausgeschlossen. Da andere Ursachen fur eine gesteigerte Oxalatbildung nicht vorlagen, wurde ein ursachlicher Zusammenhang mit der parenteralen Zufuhr von Xylit angenommen. Diesen Glukoseaustauschstoff hatte die Patientin wahrend einer totalen parenteralen Ernahrung uber 4 Wochen in einer Dosis von 3,0 g/kg/Tag (Gesamtdosis 4480 g) erhalten. Unter Hinweis auf vorangegangene autoptische Untersuchungen und jungste experimentelle Untersuchungen uber die metabolischen Schritte vom Xylit zum Oxalat werden die Moglichkeiten und Bedingungen fur eine vermehrte Bildung und Ablagerung von Oxalat nach Zufuhr von Xylit diskutiert.

Plasma exchange--how does it work?

Effective in a variety of diseases, plasma exchange is the treatment of choice in Goodpastures syndrome (1, 2), may produce considerable improvement in immunecomplex rapidly progressive glomerulonephritis (3, 4), and is the established therapy for respiratory insufficiency or drug res-istance in myasthenia graves (5, 6). In many respects as old as medicine itself, being a technically improved form of blood letting (7, 8), it was used in its original form by primitive Papuans for exorcism, and later by Hippocrates (460-377 BC) for fever, by Galen (129-199) to remove bad humors, by Avicenna (980-1037), and as leeching by army surgeons during the 1870-1 Franco-Prussian war (9). Yet while the mechanism of how bloodletting worked is no less controversial than that of plasma exchange, four main hypotheses have been proposed, namely suggestion, replacement, activation, and elimination. All bloodletting maneuvers must have a tremendous suggestive power, and their success can probably be attributed solely to this power. In modern plasma exchange the «mystique of dramatic intervention» has also been detected (10). Man wants such intervention. Thus, one of our patients with Goodpastures syndrome reported a dream she had had four weeks before the exacerbation of the disease. In this dream all the procedures were applied which were later indeed porformed. Dreams are expressions of a wish (11). But plasma exchange is more than mere suggestion, as recently shown in a double-blind trial using sham apheresis (12). Plasma exchange is more than an expensive placebo, and its additional power has been partially attributed to replacing fluid (13). This replacement definitely improved the effectiveness and compatibility of plasma exchange as compared to the «heroique» bloodletting maneuvers once performed by Broussais (17721838). In addition, replaced plasma may contain beneficial factors absent in the removed plasma. Nevertheless, a further mechanism must be postulated because plasma exchange works even with pure albumin substitution (3, 14). The most advanced and probably most ancient -