Plaquex for Kidney Disease
Mechanisms of Action
It is surmised that eicosanoids are particularly important in pathological pictures associated with limited glomerular filtration rates and urinary excretion. They are especially active in the kidneys as potential modulators for the regulation of renal haemodynamics and of glomerular filtration. In this process prostaglandins PGI2 and PGE2 exert vasodilating effects on the smooth muscle cells, whereas thromboxane A2 has a vasoconstricting action. It seems that eicosanoids provide for the maintenance of the glomerular filtration rate, and thus guarantee normal excretion of electrolytes and water, in situations when the intrarenal vessels are submitted to vasoconstricting influences. They further have tubular effects1.
In addition, also direct effects of PC can be triggered by their incorporation into renal membranes, e.g. the intracellular electrolyte transport due to improved membrane fluidity.
There are 23 studies showing the favorable effect of PC on kidney disease.
In 1961 K.Jacyszyn and R.Szymanski from Wroclaw reported about favourable effects of PC in the therapy of chronic glomerulonephritis associated with nephrotic syndrome in 11 patients2. After a 6-day treatment with 1000 mg PC i.v. daily, 6 of 9 patients showed already a reduction of edema. Serum albumin increased by 35% (0.4 g/dl), total cholesterol and total lipids fell by 13.7% and 17.2%, resp. The increase in albumin was statistically significant.
A large-scale controlled study was carried out by A.D.Petrushina et al. in 3-15 year old children suffering from acute and chronic nephritis3. 24 patients received basic treatment, 25 additionally PC i.v. for 10 days and subsequently oral PC for 20 days at a daily dose of 2 to 2.5 mg PC/kg body weight. Despite the astonishingly low dose, renal and extrarenal manifestations of the disease disappeared significantly earlier. Symptoms of intoxication were reduced (pallor and dystrophic changes of skin and mucosa, asthenia, acidosis, dystonia), blood pressure was normalized, hepatomegaly and haematuria, proteinuria, hypoalbuminemia and leucocytosis disappeared.
In a study by K.Jacyszyn et al.4 divided the patients into 2 groups:
One group consisted of 10 patients with an urea level lower than 100 mg/dl (moderate renal insufficiency), the other consisted of 9 patients with an urea level exceeding 100 mg/dl. A first 5-day phase of PC medication (1000 mg i.v. and 750 mg orally) was followed by oral administration of 1500 mg PC over 10 days.
In group 1 were achieved significant rises of creatinine, urea and sodium clearance. In 5 patients was observed a complete clinical remission including normalized blood pressure. 3 further patients exhibited clear improvements, whereas no changes were observed in another 2 cases. The 9 patients with advanced renal insufficiency showed a significant reduction of creatinine and cholesterol concentrations in the serum. The increases of creatinine clearance, urine volume and of the clearance values of sodium and potassium were also significant. The authors consider the stabilization of renal cell membranes to be one of the main effects of PC.
The favourable action of intravenously injected essential phospholipids on renal function was corroborated by L.Mainieri and A.de Lutterotti even in single i.v. administration of 250 mg PC5. They examined the renal function of 12 patients without renal disease by means of a clearance test. With the exception of 1 patient with exudative pleuritis, in all of them were found increases of the glomerular filtration rate, of renal plasma flow and of renal blood flow. This effect was observed already 30 minutes upon administration, from which the authors deduced a direct effect of PC on the kidneys.
K.Deibert and R.Juchems6 also described improved glomerular filtration after a single PC dose of 2 g, in this case orally administered. 22 patients were included into the study, among them 7 with hypertension, 4 with fatty liver, 1 with glomerulonephritis, 2 healthy persons, and other patients not suffering from renal disorders. A significant fall of serum creatinine from 1.54 to 1.37 mg/dl was found. Creatinine clearance also increased significantly from 74 to 90 ml/min. The duration of observation was 24 hours and started directly after PC administration. Also these authors postulated a direct action of PC on the cell membranes of glomeruli; it appears that the permeability coefficient is increased by the phospholipid administration.
Another study with 9 boys and girls, aged 9 months to 13.5 years, suffering from nephrotic syndrome, is of interest7. Children younger than 3 years were given 330 mg and 5 school children 700 mg PC daily. In 1 case PC was administered in combination with deltacortisone. 7 children with nephrotic syndrome presented edema at the beginning of treatment. In 2 cases the edema disappeared and were reduced in the remaining 5 patients. Reduced diuresis, which had been 300-750 ml/24 h and 160ml/24 h in 1 case, was increased by 64%. Albumin in urine was 0.5 to 10g% before treatment, and was raised by 4% in 6 children.
PC in Chronic Ambulatory Peritoneal Dialysis CAPD8
CAPD is an interesting alternative of chronic hemodialysis allowing the patient much more independence and freedom to move at considerably lower costs. The peritoneal effluent of patients on CAPD not only contains substances to be eliminated with the urine, such as electrolytes, creatinine and urea, but also a surface-active material which is probably secreted by mesothelial cells. This surface-active material, mainly consisting of phospholipids including phosphatidylcholine, was presumed to play a role in the ultrafiltration during peritoneal dialysis since it lowers surface tension, helps to repel water and acts as a lubricant. The phospholipid level in the dialysis effluent of patients who had been on CAPD for a long time are lower in comparison with patients undergoing their first days of peritoneal dialysis. A more drastic and significant decrease in phospholipids is observed even in patients with low ultrafiltration and in those with peritonitis.
The idea of N.di Paolo and co-workers was to check if the addition of PC into the dialysis fluid was able to modify the water transport in patients with low ultrafiltration and peritonitis. The authors found that during dialysis exchanges containing phosphatidylcholine (50 mg/I) the mean ultrafiltration increased significantly in the 10 patients with low ultrafiltration or peritonitis, indicating that the substance was able to restore normal physiological conditions. The significant increase observed 72 h following PC addition was maintained throughout the investigation period of 15 days. Moreover, creatinine and urea clearance increased significantly. PC seemed to act also when administered intravenously (250 mg daily) and orally (400 mg daily).
Besides seeing an increased ultrafiltration rate in kidney patients, N.V.Dombros et al.9 also observed increased ultrafiltration after PC administration even in the normal peritoneum.
PC and Gestosis
145 pregnant women with late gestosis were allotted to different groups according to the severity degree of nephropathy, and treated with conventional routine therapy (consisting of psychotropic substances, diuretics, spasmolytics, antihypertensives etc.) and additionally with vitamin E and C and/or PC10.
The more severe the gestosis was, the higher were the levels of lipid peroxidation(LPO) products in both the serum and the erythrocyte membranes, whereas antioxidative activity in serum decreased due to the reduction in the ceruloplasmin levels and - the ceruloplasmin/transferrin coefficient; microviecosity of membranes increased. In some patients, particularly in mild cases, already routine treatment led to the disappearance of symptoms. When reducing the dose, however, lipid peroxidation increased again. When additionally to routine treatment vitamins E and C were given, lipid peroxidation activity could be normalized within 7-14 days. Especially in severe nephropathy, however, this treatment was not sufficient to restore the structural and functional integrity of cell membranes. In comparison with other therapeutic measures, Lipostabil (in combination with vitamin E) favoured the antioxidative activity in serum to a larger extent (raised ceruloplasmin/transferrin coefficient): malonedialdehyde level reduced by 30% in contrast to 20% with Lipostabil alone. The inhibition of LPO activity within 7-14 days correlated with the restoration of the barrier function of the lipid bilayer of cell membranes, also in patients suffering from severe nephropathy.
Since 1963 13 investigations in a total of 684 pregnant women presenting the syndrome with various degrees of severity have been carried out; the patients were treated additionally with Essentiale ampoules and/or Essentiale forte capsules.
H.G. Mücke11 reported already in 1963 about the successful Essentiale treatment of 47 patients suffering from severe hyperemesis gravidarum. In 39 out of them symptoms disappeared already after 1-2 injections; in the remaining 8 patients 3-4 injections were necessary. The Essentiale ampoules (250 mg) were administered intravenously every other day. Good results were obtained also in patients with severe premenstrual vomiting.
At a later date, J. Hartel 12 confirmed these positive results. In a patient with intact intrauterine pregnancy, who consulted the doctor in gestation week 18, nausea and vomiting subsided already after the first Essentiale injection (250 mg EPL/day). At the end of the 8-day treatment the patient was completely free from complaints. In another 6 patients with less pronounced symptoms were also obtained
positive results with Essentiale treatment.
In a much larger number of patients (n = 568) Essentiale (in combination with basic measures) was given in the last trimester of pregnancy. In a group of 52 patients in gestation months 6-9 (n =22) or short time before delivery (n=30) it was striking to observe how rapidly clinical symptoms disappeared with daily injections of 2 Essentiale ampoules (500 mg EPL/day). On an average 7 days of treatment were necessary. Particularly edema subsided, liver and kidney function values as well as diuresis were normalized. F. Bottiglioni and R. Tirelli13 pointed out that with conventional treatment alone they rarely saw such rapid
and complete improvements.
1 Levenson, D.J., C.E. Simmons, B.M. Brenner: Arachidonic acid metabolsim and prostaglandins and the kidney. Am. J. Medicine 72 (1982) 354-374
2 Jacyszyn, K., R. Szymanski: Phospholipide in der Therapie der chronischen Glomerulonephritis mit nephrotischem Syndrom. Med. Monatsschr. 15 (1966) 819-812
3 Petrushina, A.D., V.J. Krylov, G.B. Moreva, V.A. Zhmurov, A.N. Durygin: Essentiale forte in comprehensive treatment of glomerulonephritis in children. Pediatriya (Russ.) (1987) 52-55
4 Jacyszyn, K.R., W. kornaszewski, H. Paluszynska: Essentielle Phospholipide in der Behandlung der Niereninsuffizienz. Das Deutsche Gesundheitswesen 21 (1966) 1-6
5 Maninieri, L., A. de Lutterotti: Azione favorevole dei fosfolipidi essenziati per via venosa sulla funzionalita renale-studiata per mezzo delle clearances. Rivista di Patologia e Clinica 18 (1963) 699-705
6 Deibert, K., R. Juchems: Erhöhung der glomerulären Filtration durch Phospholipide. Münch.Med. Wschr. 108 (1966) 2495-2497
7 Priscu, R., E. Manolescu, S. Sichitiu: On our experience with administration of essential phospholipids in children. Symp. Essentiale in Paediatrica Moscow, Feb. 1980
8 Di Paolo, N., U. Buoncristiani, L. Capotondo,. E. Gaggiotti, M. de Mia, P. Rossi, E. Sansoni, M. Bernini: Phosphatidylcholine and peritoneal transport during peritoneal dialysis. Nephron 44 (1986) 365-370
9 Dombros, N.V., E. Balaska, N. Savidis, A. Tourkantonis, K. Sombolas: Phosphatidylcholine increases ultrafiltration in continous ambulatory peritoneal dialysis function. Ambulatory Peritoneal Dialysis (Avram, Mm. Girodano, C. Eds.) Plenum Press
New York (1990), Chapter 8, 39-41
10 Shalina, R.I., I.B.Kusch, V.P. Oreshkina, O.A. Azizova, A.V. Kozlov, O.M. Panasenko: Antioxidants as a part of combined treatment of patients with late gestosis. Akusherstvo i ginekologiya 65 (1989) 37-41
11 Mücke, H.G.: The treatment of vomiting in pregnancy with Essentiale. Der Landarzt 39 (1963) 34-35
12 Hartel, J.: Kasuistischer Beitrag zum Thema Hyperemesis gravidarum. Aerztl. Praxis 17 (1965) 1049-1050
13 Bottiglioni, F. , R. Tirelli: Essentielle Phospholipide in der Therapie der Spätgestosen. Aerztl. Praxis 20 (1968) 2656-2657