The renin--angiotensin system gene polymorphisms and clinicopathological correlations in IgA nephropathy.

Genetic variability in the renin-angiotensin system (RAS) may modify renal responses to injury and disease progression. We examined whether RAS alleles affect severity of IgA nephropathy. These genetic variants include angiotensin I converting enzyme deletion polymorphism in intron 16 (ACE I/D), a point mutation in the angiotensinogen (AGT) gene resulting in a methionine to threonine substitution at residue 235 (M235T) and an angiotensin receptor type I (ATR) A to C transition at bp 1166 (A 1166 C). A total of 53 patients with biopsy-proven IgA nephropathy and 80 normal control subjects were recruited for study. These patients were classified into two groups according to serum creatinine at renal biopsy. Group 1 patients (n = 40) had normal renal function, serum creatinine < or = 1.5 mg/dl and group 2 patients (n = 13) had renal insufficiency with serum creatinine > 1.5 mg/dl. The blood pressure and urinary protein of group 2 patients were higher than group 1 (p < 0.01). The mean scores of histological parameters including mesangial proliferation, glomerular sclerosis (global and segmental), the interstitial fibrosis and crescent formation in group 2 patients were significantly higher than in group 1 patients (p < 0.05). The most frequent genotype in IgA patients was ID (47%) genotype, followed by II (45%) and DD (8%) genotype of ACE gene. The mean serum ACE activity in the DD group was significantly higher than in the II group (p < 0.05) but was not significantly different from that of the ID group. No statistically significant differences were found with respect to allele frequencies between IgA group 1, group 2, or between controls and all IgA patients. Furthermore, no significant difference in AGT alleles, ATR alleles frequencies was detected between groups of IgA patients, although a trend for a higher frequency of DD genotype and AGT-TT genotype were noted in IgA group 2. The combined analysis of the ACE-DD and AGT-TT genotypes did not show any genetic influence on the risk of the disease susceptibility. To resolve the true role of ACE genotype and any dependent effect on progression, larger collaborative studies are required.

Lipoprotein(a) in nephrotic syndrome.

Serum lipoprotein(a) levels were measured in 27 patients with idiopathic nephrotic syndrome (NS), 14 patients with systemic lupus erythematosus (SLE) and 30 healthy controls. Lp(a) levels were significantly elevated in both idiopathic NS (53.4 + 36.2) and SLE (49.3+ 41.9) compared with controls (9.5+ 5.7) (p < 0.001). Fifty nine percent of idiopathic NS and 50 percent of SLE had Lp(a) more than 30 mg/dl. In 19 patients with idiopathic NS, serum Lp(a) levels fell markedly in 12 patients who responded to prednisolone therapy while, 7 patients with partial and no response had serum Lp(a), cholesterol, triglycerides and albumin levels not different from pretreatment period vs 6 months therapy. Lp(a) levels correlated significantly with proteinuria, serum cholesterol and triglycerides (r = 0.8, 0.6, 0.6) in idiopathic nephrotic syndrome and correlated inversely with serum albumin (r = -0.9). The SLE patients had the same pattern of correlation among these parameters and Lp(a) levels except for triglycerides. The high levels of Lp(a) in the NS could be one of the risk factors for atherosclerosis and thrombotic events associated with this disorder. In conclusion, the present study confirmed that patients with idiopathic NS and SLE had markedly increased serum level of Lp(a), in conjunction with other lipid abnormalities. The serum Lp(a) levels decreased substantially in all NS patients who experienced remission. In addition, the study also demonstrated a relationship between serum Lp(a) levels and serum albumin, cholesterol and triglycerides. An elevated Lp(a) level may be useful in guiding the physician towards more aggressive care to detect coronary artery disease early in patients at risk.

Reduced free radical scavengers and chronic renal failure.

Endogenous oxygen radical scavengers such as glutathione peroxidase (GSH-Px), catalase (CAT), glutathione and vitamin E are powerful regulatory systems against free radical toxicity. These oxidative injuries are increased in patients with chronic renal failure leading to various abnormalities including anemia. In this study, activities of GSH-Px, CAT, glutathione and vitamin E were measured in the erythrocytes of 54 chronic renal failure patients compared with 32 healthy controls. GSH-Px activities were lower significantly from controls (20.5 +/- 6.79 vs 28.3 +/- 9.0 u/gHb, p < 0.001). Erythrocytes CAT (6.52 +/- 2.3 vs 7.54 +/- 1.9 u/gHb, p < 0.05), glutathione (63.59 +/- 20.2 vs 75.1 +/- 6.3 mg/dl, p < 0.05) vit. E (2.23 +/- 0.53 vs 3.38 +/- 0.44 g/ml RBC, p < 0.001) were also lower in the patients group. Plasma malondialdehyde (MDA) known as lipid peroxidation product was higher significantly than controls (p < 0.001). Abnormal erythrocyte osmotic fragility test, expressed by glycerol lysis time (GLT50) was found in the patients group (p < 0.001) and correlated significantly with RBC vitamin E. Results demonstrated defects in erythrocytes enzymatic antioxidant defense mechanism in chronic renal failure patients. To improve antioxidant systems seems to be promising in preventing hemolysis and anemia in these patients.

Role of lipid peroxidation, trace elements and anti-oxidant enzymes in chronic renal disease patients.

Plasma Selenium (Se), Zinc (Zn), Copper (Cu) and Aluminium (Al) levels, red blood cell vitamin E and antioxidant enzymes, glutathione peroxidase (GPX) and catalase activity were studied in 54 patients with renal diseases of different levels of kidney dysfunction. Group I (serum creatinine < 2 mg/dl), Group II (serum creatinine 2-4 mg/dl), Group III (serum creatinine 4.1-8 mg/dl), Group IV (serum creatinine 8.1-12 mg/dl) Group V (serum creatinine > 12 mg/dl); thirty two healthy subjects are controls. Plasma Zn (ug/L) and red blood cell vitamin E (ug/ml PRC) were decreased more significantly than controls (1348.59 +/- 43.72 vs 1318.89 +/- 45.62, and 3.38 +/- 0.45 vs 2.23 +/- 0.52) while plasma Selenium and Copper are within normal ranges. Plasma GSH-PX and catalase activity (IU/ml PRC) were also decreased (28.26 +/- 9.01 vs 20.48 +/- 6.79 and 7.54 +/- 1.91 vs 6.52 +/- 2.31) more significantly than controls. Lipid peroxidation products, plasma (umol/L) and urine malonaldehyde (MDA, umol/Ccr) were elevated (7.29 +/- 3.39 vs 92.94 +/- 61.66, and 32.08 +/- 24.60 vs 246.14 +/- 325.66) significantly (p < 0.0001). The lipid peroxidation abnormalities were seen in patients with normal renal function, which supports the role of oxidative stress early in the course of renal disease. Urine ammonia per GFR was also increased as well as urine B2m and NAG. There was no correlation between lipid peroxidation product (MDA) and any of the antioxidant enzymes, vitamin E, urine NH3, B2m, protein or NAG except urine ammonia and MDA per nephron which correlate with severity of kidney dysfunction which confirmed the role of complex processes in the progression of chronic renal failure. The early intervention to decrease oxygen consumption either by dietary protein restriction antioxidants such as vitamin E supplement or calcium channels blockers may be of value in preserving renal function in the setting of chronic renal failure.

Lipoproteins and lipid peroxidation abnormalities in patients with chronic renal disease.

Increasing experimental and clinical evidence suggests that lipoproteins and lipid peroxidation can be important modulators in progressive kidney disease. A group of 54 patients with varying degrees of kidney impairment was studied to find the abnormalities in lipoproteins and lipid peroxidation. Lipoproteins and lipid peroxidation products, malondialdehyde (MDA) were measured in the plasma of 54 chronic renal disease patients CGN 33, nephrosclerosis 11, 7CTIN, 1PCKD, unknown 2 and compared with values obtained from 32 healthy controls. The patients were divided into 5 groups according to serum creatinine levels: Group 1 (serum creatinine of 2 mg/dl), group 2 (S. creatinine > 2-4 mg/dl), group 3 (S. creatinine > 4-8 mg/ dl), group 4 (S. creatinine > 8-12 mg/dl), group 5 (S. creatinine > 12 mg/dl). Plasma cholesterol was higher significantly than controls in patients with group 1, 2 and 3 (p < 0.01, < 0.001, < 0.05) respectively while plasma LDL-chol was statistically significantly different from controls only in group 2 patients (p < 0.001). Plasma VLDL-chol, beta-VLDL-chol, triglycerides, ratio of chol/HDL and LDL/ HDL showed high levels in all groups compared with controls but more evident in patients of group 2. Plasma HDL-chol decreased during the progression of renal failure. All groups had significantly elevated plasma malonyldialdehyde (MDA) vs controls (p < 0.001), especially highest value was found in group 2. Triglycerides, beta-VLDL chol, VLDL-chol LDL/HDL, chol/HDL correlated very closely with plasma MDA levels and also with serum creatinine. Patients with chronic renal disease showed lipoprotein abnormalities and accelerated lipid peroxidation. The evidence was more marked in patients with normal to mild renal insufficiency which suggested the role of oxidative stress early in the course of nephron injury.

Glomerulonephritis in beta-thalassemia Hb-E disease: clinical manifestations, histopathologic studies and outcome.

We presented 8 patients with beta-thal/Hb E with glomerular diseases. Diverse glomerular lesions were seen, but diffuse endocapillary glomerulonephritis was the most common. The clinical manifestations of acute glomerulonephritis in beta-thal/Hb E differed from typical cases in the older age group, female preponderance, longer duration of edema, less hypertension, marked proteinuria, hypoalbuminemia and hypertriglyceridemia and also a longer period of recovery but their outcome was still favorable despite many risk factors of renal injury. Renal biopsy was necessary in doubtful cases to detect the correct diagnosis and give proper management. The association and mechanism of glomerulonephritis in these patients require further prospective study.

Lupus nephritis in males: 8-year experience at Siriraj Hospital.

During 1984 to 1991, 54 out of 569 lupus nephritis patients at Siriraj Hospital were male (F:M sex ratio = 10:1). Mean age of the males was 29.8 +/- 14.6 years, range 12 to 69. The three most common extrarenal manifestations were anemia, cutaneous, and musculoskeletal involvement (74.5, 51.1, and 43.9%, respectively). The major renal manifestations were edema (75.9%) with heavy proteinuria over 3.5 g/day in 62.2% and nephrotic/nephritic findings in 51.9% of cases. Hypertension was found in 35.2%. Mean serum creatinine was 2.0 +/- 1.4 mg/dl while 60.5% of cases had creatinine clearance below 50 ml/minute. Mean serum albumin was 2.6 +/- 0.8 g/dl, cholesterol 262.8 +/- 129.5 and triglycerides 343.2 +/- 244.6 mg/dl. Interestingly, hypercholesterolemia (> 250 mg/dl) was found only in 44.8% of cases with nephrotic syndrome. Antinuclear antibody was demonstrated in 91.5%, anti-dDNA antibody in 64.4% and LE cells in 40.4% of cases. Renal biopsy was done in 45 patients and 30 cases (66.7%) were classified as diffuse proliferative nephritis (WHO type IV), 15.6% of type II, 6.7% each of type III and V, with the rest of type V plus IV (4.4%). Tubulointerstitial inflammation was found in 77.3% of cases. During the follow-up period (42 +/- 35.8 months), 6 patients died. The cause of death were uremia in 3, infection in 2, and cardiac failure in 1. By life-table analysis, the probabilities of survival for 1 and 5 years were 89.5 and 80.6%, respectively. In comparison between sexes, except for a higher amount of urinary protein excretion (4.5 +/- 3.1 vs 3.5 +/- 3.0 g/day, p < 0.05), there were no statistically significant differences in clinical and pathological parameters, and probability of survival.

Lipoprotein abnormalities in adult nephrotic syndrome.

The lipid and lipoprotein profiles including apolipoprotein A1 and B100 are measured in 50 idiopathic nephrotic patients (males 26, females 24) with mean age of 32 + 13.6 yrs, serum creatinine 1.32 +/- 0.43 mg/dl compared with 50 age matched normal controls. The renal histology consist of IgM nephropathy 70 per cent, membranous 12 per cent, and IgA 2 per cent. The serum cholesterol, triglycerides, LDL- cholesterol, VLDL-cholesterol, apolipoprotein B (521.6 +/- 201.6, 291.4 +/- 156.2, 438.8 +/- 207.4, 58.3 +/- 31.2, 265.1 +/- 119.8) are statistically significantly higher than controls (p < 0.001). The HDL-cholesterol (30.2 +/- 16.1) is also significantly lower than controls (p < 0.001) but apolipoprotein A is not different from normal subjects. The most common hyperlipoprotein type is type IIb (66%), less common are type IIa (22%), IV (6%) and III (4%) respectively. There is no correlation between serum lipids, lipoproteins and urinary protein, serum albumin, and histological diagnosis. The ratio of cholesterol: HDL, LDL: HDL and Apo A1: B are all significantly higher than normal control (p < 0.001) and correlate with urinary protein levels. This study shows that the nephrotic patients who have persistent heavy proteinuria have dyslipidemia which is highly atherogenic and probably increases the incidence of coronary heart disease.

Urinary constituents in an endemic area of stones and renal tubular acidosis in northeastern Thailand.

Nephrolithiasis and endemic renal distal tubular acidosis are common in northeastern Thailand. The etiology is still unknown. It is generally accepted that urine electrolytes influence the capacity of urine to inhibit or promote renal and also bladder stones. The purpose of this study was to analyse the composition of the urine in the indigenous population in the northeast area and compare their values with data obtained from a group of age matched adults, living in Bangkok. Twenty-four hour urine samples from 23 normal adult villagers from six villages within the province of Khon Kaen and 34 normal adults living in Bangkok were collected, and the daily excretion of creatinine, uric acid, calcium and inorganic phosphate, sodium, potassium, chloride, magnesium and oxalate were assayed. Daily urinary sodium, potassium, chloride and phosphate of the villagers were significantly lower than those of Bangkokians. No difference in the urinary excretion of calcium, magnesium, uric acid, oxalate and creatinine was found. The Na/Ca, and Ca/PO4 ratios of villagers were significantly lower than those of the Bangkok subjects. The villagers excreted significantly lower amounts of Na in the face of relatively higher urinary Ca. The above data, combined with our previous study showing the low values of urinary citrate in the villagers in the same areas, strongly indicate that the indigeneous population is at high risk in developing urolithiasis. The causes for these electrolyte abnormalities are still unknown. Low contents of the major electrolytes in their diets might play an important role. Low phosphate output indicates low protein diets.(ABSTRACT TRUNCATED AT 250 WORDS)