dinoprost and Glomerulonephritis

Eight patients with chronic glomerulonephritis were treated with either naproxen or sulindac in an open randomized study to observe their effects on the urinary excretion of prostaglandins and renal function. Both drugs were given for 7 days. Naproxen caused a decrease (p less than 0.01) of 80% in prostaglandin PGE2 and decrease (p less than 0.01) of 55% in prostaglandin PGF2 alpha. Sulindac caused a decrease (p = 0.01) of 37% in PGE2 and a decrease (p less than 0.05) in PGF2 alpha of 13%. The decrease in urinary excretion of prostaglandins were greater (p less than 0.05) during the naproxen treatment. Naproxen caused a decrease (p less than 0.05) in 24-hour creatinine clearance of 14 ml/min, an increase (p less than 0.05) in plasma urea of 1.0 mmol/l, an increase (p less than 0.05) in plasma potassium of 0.4 mmol/l and a decrease (p less than 0.01) in 24-hour urinary excretion of albumin of 11 mumol. Sulindac did not change any of these parameters significantly. In conclusion, sulindac affects renal prostaglandin synthesis to a significantly minor degree than naproxen and contrary to naproxen it does not influence the renal function in patients with chronic glomerular disease.

Topics: Adult; Chronic Disease; Clinical Trials as Topic; Creatinine; Dinoprost; Dinoprostone; Female; Glomerulonephritis; Humans; Indenes; Kidney; Male; Middle Aged; Naproxen; Prostaglandins E; Prostaglandins F; Random Allocation; Sulindac

Nine patients with chronic glomerulonephritis were investigated in a controlled, double-blind, crossover study to assess the efficacy of prostaglandin E1 (PGE1) infusion therapy. Three-hour intravenous infusions of PGE1 (100 micrograms/day) and placebo were performed every day for three weeks, respectively. Improvement of renal function was demonstrated by statistical u-test (p less than 0.01) and x2-test (p less than 0.05). Three weeks infusion of PGE1 tended to increase creatinine clearance. PGE1 infusion significantly decreased the serum level of creatinine as compared with the placebo infusion (p less than 0.05). The urinary excretion of protein, however, did not change with PGE1. It was concluded that PGE1 infusion is effective in improving renal function in patients with chronic glomerulonephritis.

Topics: Alprostadil; Chronic Disease; Dinoprost; Double-Blind Method; Female; Glomerulonephritis; Humans; Male; Prostaglandins E; Prostaglandins F

To evaluate the status of oxidative stress in patients with different primary glomerular diseases (PGD) which have differential predisposition to renal failure.. Seventy-three patients with PGD and 50 controls were enrolled in the study. They were sub-grouped into non-proliferative glomerulonephritis (NPGN) and proliferative glomerulonephritis (PGN). Levels of serum malondialdehyde (MDA), reactive nitrogen intermediates (RNI), plasma total homocysteine (tHcy), urine 8-isoprostane (8-IP), RBC thiols, glutathione-S-transferase (GST) and serum superoxide dismutase (SOD) were measured spectrophotometrically.. PGD patients showed a significant increase in MDA, RNI, tHcy, 8-IP levels (P < 0.05) and decreased SOD, total thiols and protein bound thiol levels as compared to controls (P < 0.05). Significantly higher levels of tHcy, MDA and 8-IP (P < 0.05) and lower SOD enzyme activity (P < 0.05) were observed in PGN group as compared to NPGN and control groups. These changes remained significant even after adjustment was made for creatinine.. Oxidative stress in PGN is significantly higher than NPGN, indicating higher oxidative stress in these patients, independent of degree of renal dysfunction.

Topics: Adolescent; Adult; Animals; Dinoprost; Glomerulonephritis; Homocysteine; Humans; Kidney Diseases; Kidney Glomerulus; Malondialdehyde; Middle Aged; Oxidative Stress; Reactive Nitrogen Species

Aging is characterized by renal functional and structural abnormalities resembling those observed in diabetes. These changes have been related to the progressive accumulation of advanced glycation end-products (AGEs) and cumulative oxidative stress occurring in both conditions. We previously reported that galectin-3 ablation is associated with increased susceptibility to diabetes- and AGE-induced glomerulopathy, thus indicating a protective role of galectin-3 as an AGE receptor. To investigate the role of the AGE/AGE receptor pathway in the pathogenesis of age-related renal disease, we evaluated the development of glomerular lesions in aging galectin-3 knockout (KO) vs. wild-type (WT) mice and their relation to the increased AGE levels and oxidative stress characterizing the aging process. KO mice showed significantly more pronounced age-dependent increases in proteinuria, albuminuria, glomerular sclerosis, and glomerular and mesangial areas, starting at 18 mo, as well as renal extracellular matrix mRNA and protein expression, starting at 12 mo vs. age-matched WT mice. Circulating and renal AGEs, plasma isoprostane 8-epi-PGF2alpha levels, glomerular content of the glycoxidation and lipoxidation products N(epsilon)-carboxymethyllysine and 4-hydroxy-2-nonenal, and renal nuclear factor-kappaB activity also increased more markedly with age in KO than WT mice. AGE levels correlated significantly with renal functional and structural parameters. These data indicate that aging galectin-3 KO mice develop more pronounced changes in renal function and structure than coeval WT mice, in parallel with a more marked degree of AGE accumulation, oxidative stress, and associated low-grade inflammation, thus supporting the concept that the AGE/AGE receptor pathway is implicated in age-related renal disease.

Topics: Age Factors; Aging; Aldehydes; Animals; Body Weight; Dinoprost; Extracellular Matrix; Galectin 3; Glomerulonephritis; Glycation End Products, Advanced; Kidney Glomerulus; Lysine; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Oxidative Stress; Receptor for Advanced Glycation End Products; Receptors, Immunologic; RNA, Messenger; Transforming Growth Factor beta; Transforming Growth Factor beta1

With radioimmunoassay, daily urinary levels of prostaglandins E2 and F2 alpha (PGE2, FGF2 alpha were measured in 45 patients with hypertensive disease, 13 patients with chronic diffuse glomerulonephritis and 14 healthy persons. A progressive reduction in urinary PGE2 excretion was found to accompany the occurrence of labile arterial hypertension (AH), its stabilization, and development of malignant AH in patients with hypertensive disease or chronic diffuse glomerulonephritis. When labile AH developed, urinary PGF2 alpha excretion was increased, but when AH stabilized, its excretion became increased up to the baseline level. The specific features of malignant AH are significantly higher urinary PGF2 alpha and sharply greater PGF2 alpha/PGE2 coefficient. The identified abnormal metabolism of renal prostaglandins may contribute to the stabilization of blood pressure at a high level and to the development of malignant AH.

Topics: Circadian Rhythm; Dinoprost; Dinoprostone; Glomerulonephritis; Humans; Hypertension; Hypertension, Malignant; Reference Values

While much is known regarding acute nephrotoxic serum (NTS)-induced glomerular injury, the glomerular dynamics and pathophysiologic mediators of the more relevant chronic autologous phase remain poorly defined. Studies were performed in rats 14 d after injection of rabbit serum (n = 6), NTS in the absence (n = 6), or presence, of a cyclooxygenase inhibitor, ibuprofen (n = 6) or a thromboxane A2 (TxA2) receptor antagonist, L-670,596 (n = 5). A mesangial macrophage/monocyte infiltrate was noted with equal intensity in all NTS-treated rats. Glomerular generation rates of prostaglandin (PG) E2, PGF2a, and TxA2 in nephritic kidneys were dramatically increased as compared to controls. 2 wk after NTS, there was an increase in glomerular plasma flow rate (SNPF), attainment of filtration pressure disequilibrium, and augmentation of net transcapillary hydraulic pressure difference (delta P). Glomerular filtration rate (GFR), however, was reduced, due to a marked fall in the glomerular capillary ultrafiltration coefficient (Kf). Cyclooxygenase inhibition resulted in normalization of glomerular eicosanoid generation rates, amelioration of proteinuria, afferent vasoconstriction, and normalization of SNPF, delta P, Kf, and GFR. Selective antagonism of TxA2 also led to preservation of Kf, but was without effect on SNPF, thereby leading to elevated values for GFR. Thus, in contrast to the pathophysiologic role of arachidonate-lipoxygenase products in the early heterologous phase, PG-mediated vasodilatation and TxA2-induced reductions in Kf and GFR underlie glomerular functional changes during autologous mesangioproliferative glomerulonephritis.

Topics: Animals; Blood Pressure; Dinoprost; Dinoprostone; Glomerular Filtration Rate; Glomerulonephritis; Hematocrit; Male; Platelet Activating Factor; Proteinuria; Rats; Thromboxane A2; Vascular Resistance

The quantity of protein in the diet modulates glomerular function. To study the effect of dietary protein intake on glomerular eicosanoid production, rats were randomized to either a high- (40%) or low- (8.5%) protein isocaloric diet. Ten to fourteen days later glomeruli were isolated and incubated in the absence (basal) and presence (stimulated conditions) of arachidonic acid, and production rates of prostaglandin (PG) E2, PGF2 alpha, and thromboxane B2 (TxB2) were determined by direct radioimmunoassay. Under basal conditions, glomerular production of all three eicosanoids was significantly greater in rats ingesting the high-protein diet. Glomerular production of PGE2 and TxB2 was also greater in animals fed the high-protein diet in the presence of arachidonic acid, suggesting that glomerular cyclooxygenase activity was augmented. In contrast, ingestion of a high-protein diet was not associated with a significant increase in eicosanoid production by renal papillae or in TxB2 release by clotting blood. To investigate the potential role of the renin-angiotensin system in the dietary protein-induced modulation of glomerular eicosanoid production, rats ingesting a high- or low-protein diet were randomized to treatment with an angiotensin-converting enzyme inhibitor or no therapy. Enalapril attenuated the dietary protein-induced augmentation in glomerular eicosanoid production. This effect occurred only when administered in vivo, since the active metabolite enalapril did not alter PGE2 production by isolated glomeruli when added in vitro. Dietary protein intake also modulated glomerular eicosanoid production in three models of experimental renal disease in the rat (streptozotocin-induced diabetes mellitus, Heymann nephritis, and partial renal ablation).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Diabetes Mellitus, Experimental; Dietary Proteins; Dinoprost; Dinoprostone; Enalapril; Glomerulonephritis; Kidney Glomerulus; Male; Peptidyl-Dipeptidase A; Radioimmunoassay; Rats; Rats, Inbred Strains; Renin-Angiotensin System; Thromboxane B2

The effects of curantyl (dipiridamole) on the excretion of prostaglandins E2 and F2 alpha (PGF2 alpha and PGF2 alpha) and renal hemodynamics (RHD) were studied in patients with hypertensive nephritis in an acute test and during prolonged (up to 21 mos) single-agent therapy. In the acute test curantyl increased PG excretion in 15 out of 18 patients by 86.8 +/- 17.6%, mainly at the expense of PGE2 (133.2 +/- 33.1%), and renal blood flow in 11 out of 12 patients by 32.1 +/- 7.7%. During prolonged therapy curantyl also raised PGE2 excretion and improved RHD (raised renal blood flow, glomerular filtration and decreased renal vascular resistance). Besides, during prolonged single-agent therapy curantyl reduced renin plasma activity, increased circulating blood volume, insignificantly reduced BP, and possessed an antiproteinuric and antihematuric effect. It is concluded that curantyl can stimulate PG renal biosynthesis improving RHD in hypertensive nephritis that can have a beneficial effect on a course of this disease.

Topics: Adult; Chronic Disease; Dinoprost; Dinoprostone; Dipyridamole; Female; Glomerulonephritis; Hemodynamics; Humans; Kidney; Male; Middle Aged; Renal Circulation

We have examined the urinary excretion of stable immunoreactive eicosanoids in 23 female patients with systemic lupus erythematosus (SLE), 16 patients with chronic glomerular disease (CGD), and 20 healthy women. SLE patients had significantly higher urinary thromboxane B2 (TXB2) and prostaglandin (PG) E2 excretion and significantly lower 6-keto-PGF1 alpha than did healthy women. In contrast, CGD patients only differed from controls for having reduced 6-keto-PGF1 alpha excretion. The group of SLE patients with active renal lesions differed significantly from the group with inactive lesions for having a lower creatinine clearance and urinary 6-keto-PGF1 alpha and higher urinary TXB2. Higher urinary TXB2 excretion was associated with comparable platelet TXB2 production in whole blood, undetectable TXB2 in peripheral venous blood, and unchanged urinary excretion of 2,3-dinor-TXB2. A significant inverse correlation was found between urinary TXB2 and creatinine clearance rate (CCr). In contrast, the urinary excretion of 6-keto-PGF1 alpha showed a significant linear correlation with both CCr and para-aminohippurate clearance rate (CPAH). In four SLE and seven CGD patients, inhibition of renal cyclooxygenase activity by ibuprofen was associated with a significant reduction in urinary 6-keto-PGF1 alpha and TXB2 and in both CCr and CPAH. However, the average decrease in both clearances was 50% lower in SLE patients than in CGD patients, when fractionated by the reduction in urinary 6-keto-PGF1 alpha or PGE2 excretion. We conclude that the intrarenal synthesis of PGI2 and TXA2 is specifically altered in SLE. Such biochemical alterations are associated with changes in glomerular hemodynamics and may play a role in the progression of SLE nephropathy.

Topics: Adolescent; Adult; Aged; Blood Platelets; Chronic Disease; Dinoprost; Dinoprostone; Epoprostenol; Female; Gas Chromatography-Mass Spectrometry; Glomerulonephritis; Humans; Ibuprofen; Kidney; Kidney Function Tests; Lupus Erythematosus, Systemic; Middle Aged; Prostaglandins E; Prostaglandins F; Radioimmunoassay; Thromboxane A2; Thromboxane B2

Topics: Acute Disease; Child; Chronic Disease; Dinoprost; Dinoprostone; Glomerulonephritis; Humans; Prostaglandins E; Prostaglandins F

We studied prostaglandins and kallikrein urinary excretion in 14 children with acute poststreptococcal glomerulonephritis within 48 hours of hospital admission (period A), and again, 4-6 weeks later, when they were clinically recovered (period B). Seventeen apparently healthy children were studied as controls. The results (mean +/- SEM) indicate that PGE2 urinary excretion (ng/kg/day) was diminished during both periods of study (control group = 2.06 +/- 0.43, patients = period A 0.91 +/- 0.28 [P less than 0.02], period B 0.92 +/- 0.21 [P less than 0.02]). PGF2 alpha urinary excretion (ng/kg/day) was also suppressed during period A, but not during period B when large individual variability existed (control group = 7.10 +/- 1.07, patients period A 3.56 +/- 0.66 [P less than 0.001], period B 10.51 +/- 5.01 [NS]). Kallikrein urinary excretion (EU/kg/day) was also depressed during the acute phase and remained low during convalescence (control group = 0.492 +/- 0.1, patients period A 0.143 +/- 0.044 [P less than 0.001], period B 0.265 +/- 0.093 [P less than 0.02]). There was no difference in PGE/PGF ratio between controls and patients in the periods of study (control 0.328 +/- 0.055, period A 0.395 +/- 0.144, period B 0.384 +/- 0.128). Urine volume (ml/day) was lower in period A (582 +/- 75.8) but comparable in period B (1020 +/- 140.2) and control children (1210 +/- 80.2). No correlation could be found between the urinary excretion of PGE2, PGF2 alpha and kallikrein with any of the following parameters: urinary or serum sodium and potassium, serum or urinary osmolality, Cosm, urine flow, plasma renin activity, plasma or urinary aldosterone, hypertension or fluid retention.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acute Disease; Adolescent; Age Factors; Child; Child, Preschool; Convalescence; Dinoprost; Dinoprostone; Female; Glomerulonephritis; Humans; Kallikreins; Male; Prostaglandins E; Prostaglandins F

An accelerated model of nephrotoxic serum nephritis (NTN) was induced in two groups of Sprague-Dawley rats on the following regimens: (a) a diet deficient in essential fatty acids that contained 20% coconut oil (rats A); (b) a diet supplemented with essential fatty acids that contained 20% safflower oil (rats B). Animals from both groups developed a severe proteinuria reaching its maximum 4 days after the injection of nephrotoxic serum (NTS). Kidney tissue was studied by light and immunofluorescent microscopy 2 to 21 days after NTS injection. The glomeruli of rats A exhibited much more fibrinoid deposition than did those of rats B. A comparable glomerular infiltration by mononuclear cells was observed in both groups of animals between the 2nd and 5th day following the injection of NTS. The number of intrinsic glomerular cells incorporating 3H-thymidine in vivo, however, was significantly lower in rats A than it was in rats B. The outgrowth capacity of glomerular cells in vitro was significantly lower in glomerular explants from rats A than it was in glomerular explants from rats B. These findings demonstrate that, in this model of rat NTN, a diet deficient in essential fatty acids has no major effects on the course of the disease during the first 3 weeks following NTS injection. They further show that the proliferation of intrinsic glomerular cells can be modulated by altering prostaglandin metabolism.

Topics: Animals; Cell Division; Diet; Dinoprost; Dinoprostone; Fatty Acids, Essential; Female; Glomerulonephritis; In Vitro Techniques; Kidney Glomerulus; Nephritis; Prostaglandins E; Prostaglandins F; Rats; Rats, Inbred Strains

Thirteen patients with active IgA glomerulonephritis (IgA GN), ten patients with a history of Henoch-Schönlein glomerulonephritis (HS GN) and nine healthy controls were studied during hydropenia (HP) and 3% volume expansion (VE) with isotonic saline. Clearance of inulin and para-aminohippurate, urinary excretion of Na, immunoreactive prostaglandin F2 alpha (PGF2 alpha) and 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) were determined. The patients with a history of HS GN had normal blood pressure and renal function. As in the controls, the urinary excretion of PGF 2 alpha decreased and the excretion of 6-keto-PGF1 alpha increased during VE. In the patients with IgA GN the glomerular filtration rate (GFR) was normal, markedly reduced and supernormal. Five patients had hypertension and an increased NA excretion in relation to the GFR during VE. As a group, the patients with IgA GN increased their urinary excretion of 6-keto-PGF1 alpha during VE, while the excretion of PGF2 alpha did not change. In relation to the GFR, the urinary excretion of PGF2 alpha and 6-keto-PGF1 alpha was markedly increased in two patients with low GFR, which implies that these substances play a role in advanced renal disease. VE had little effect on PG excretion in these patients. In the hypertensive patients the urinary excretion of PGF2 alpha and 6-keto-PGF1 alpha was the same as in those with normal blood pressure. PGs are therefore not likely to mediate the increased natriuretic response to VE in hypertension.

Topics: 6-Ketoprostaglandin F1 alpha; Adolescent; Adult; Child; Dinoprost; Female; Glomerular Filtration Rate; Glomerulonephritis; Humans; Immunoglobulin A; Male; Prostaglandins F; Water-Electrolyte Imbalance