Lipoprotein(a) levels in the nephrotic syndrome.

We investigated serum lipoprotein(a) [Lp(a)] levels in 20 patients with the nephrotic syndrome. Lp(a) levels in the nephrotic syndrome patients were significantly higher than those in a control group (30.4 +/- 22.5 vs 10.4 +/- 17.7 mg/dl). Overall, the serum Lp(a) and lipid levels showed no relationship, but on an individual basis the serum Lp(a) level varied with the serum levels of total cholesterol and low density lipoprotein cholesterol in the nephrotic syndrome patients. Our findings suggest that a decrease in serum albumin led to increased hepatic Lp(a) synthesis. It is well known that thrombotic disease supervenes on hypercoagulability in the nephrotic syndrome, so the determination of Lp(a) levels in these patients may provide information which is useful for preventing thrombotic complications.     

Penicillamine and nephrotic syndrome

BACKGROUND: Penicillamine (PA) treatment may be associated with a wide spectrum of adverse effects. There are many case reports and small series of PA-induced nephrotic syndrome (NS). In addition to our patient, in this study, we review all the cases of NS due to PA treatment in the English literature. METHODS: A retrospective Medline search was done for the years 1963-2004 using the terms "penicillamine" and "proteinuria" or "penicillamine" and "nephrotic". Cases were also located through article references. Cases were included in our review only if they had enough clinical and laboratory data and if the NS was considered by the authors to be mainly or solely due to PA treatment. Diagnosis of the patient, dose and duration of PA treatment, maximal amount of proteinuria, kidney function, urine analysis, serological markers, clinical data, kidney biopsy results, treatment, and course of proteinuria were documented. RESULTS: Sixty-three patients met our criteria. The female/male ratio was 40:23. Seventy-five percent of the patients had rheumatoid arthritis (RA). Mean age at diagnosis of NS was 44 (+/-S.D. 14) years. Mean dose of PA at diagnosis was 1.09 (+/-S.D. 0.413) g. Mean duration of PA treatment prior to proteinuria was 7.6 (+/-S.D. 3.90) months and mean duration of PA treatment until diagnosis of NS was 11.9 (+/-S.D. 18.8) months. Peak level of proteinuria was 10.79 (+/-S.D. 9.436) g. Some 33% of the patients developed mild to moderate renal failure at the time of diagnosis of NS, and one patient developed acute renal failure. Fifty-five percent of the patients had membranous glomerulonephritis and 27% had minimal change disease. Twelve patients were treated with corticosteroids (CS) at a dose ranging from 40 to 90 mg/day. In the overwhelming majority of patients, the proteinuria decreased significantly or disappeared within 7 months after stopping PA treatment. Patients treated with CS had a faster response. Five patients died, two of them from the CS-treated group, due to sepsis. CONCLUSION: The mean duration of PA treatment prior to the development of NS is nearly 1 year (5 months after the development of proteinuria). The most common histopathological finding is membranous glomerulonephritis. Most patients will have a significant reduction in, or disappearance of, proteinuria within 7 months after stopping PA treatment. The decrease in proteinuria is faster with CS treatment.     

Idiopathic nephrotic syndrome in the elderly

The most frequent primary glomerular diseases (PGD) associated with nephrotic syndrome (NS) in the elderly are membranous nephropathy (MN), minimal change nephropathy (MCN), and focal and segmental glomerulosclerosis (FSGS). In older patients MN may be secondary to drugs or neoplasia in 20 to 25% of cases. The natural renal outcome of idiopathic MN is similar in elderly patients and in those of the second age. However, elderly patients are more exposed to the extra-renal complications of NS. Corticosteroids alone do not seem to modify the course of the disease. A 6-month regimen with corticosteroids alternated to chlorambucil, which has proven to improve the outcome of MN in adults, may increase the chances of remission and protect renal function also in the elderly patients but side effects increase with age. Elderly patients with MCN are more prone than younger adults to the complications of the NS and to the development of renal failure. Only 60% of older patients enter remission with an 8-week course of prednisone, but about 80% can achieve complete remission with corticosteroids if treatment is prolonged to 12–16 weeks. Relapses are more rare in the elderly. In patients with contraindications to prolonged corticosteroid therapy, a course of 12 weeks with a cytotoxic agent may obtain stable remission in most cases. Little information is available about the natural course and the management of idiopathic FSGS in the elderly. A recent report showed that more than 40% of older patients may obtain stable remission after an initial treatment with corticosteroids for 6 months. For those patients who do not respond or have contraindications to steroid therapy, a cautious trial with cyclophosphamide may be tried.     

Beta-thromboglobulin levels in the nephrotic syndrome

Beta-thromboglobulin (BTG), a platelet-specific protein released on platelet aggregation, was measured in 13 patients with clinical and biochemical evidence of the nephrotic syndrome. All 13 patients had increased concentrations of BTG compared to both 10 normal controls and to 12 non-nephrotic azotemic patients (p < 0.001). In five patients with the nephrotic syndrome in remission, the BTG levels returned to normal. These results support the contention that the nephrotic syndrome is associated with a state of hypercoagulability and suggest that increased platelet aggregation may be the primary underlying mechanism.     

Lipoprotein composition in diabetes mellitus.

Lipoprotein cholesterol and triglyceride levels have been determined in normal and diabetic Pima Indian women aged 20-35, HDL cholesterol levels were lower, LDL cholesterol levels were higher, and the ratio of HDL cholesterol/LDL cholesterol, a reflection of lipoprotein cholesterol distribution, was lower in the diabetics compared to the normals. VLDL triglyceride levels were also elevated in the diabetics. An analysis of lipoprotein composition suggested that these changes primarily reflect changes in numbers of particles, since lipid composition and lipid/protein ratios were similar in lipoproteins isolated from normals and diabetics. The ratio of ester/free cholesterol in LDL and HDL was lower in normal Pima Indians than in a comparable group of Caucasians, although plasma LCAT activity was not significantly different. The data indicate that diabetes may be associated with shifts in distribution of LDL and HDL, as well as with increases in VLDL.     

Thyroid function in the nephrotic syndrome

Serum Total Thyroxine (T4), Triiodothyronine (T3), Free Thyroxine (FT4), Free Triiodothyronine (FT3) Reverse Triiodothyronine and T3 Resin Uptake (T3RU) as well as basal and post stimulating TSH were measured in twenty clinically euthyroid patients with the nephrotic syndrome. In comparison with control values, our patients showed (1) significantly lowered mean serum TBG levels (p less than 0,05) (2) unmodified mean serum T3, FT3 and rT3 values (3) significantly lowered mean serum T4 and FT4 levels (p less than 0,001 and p = 0,027 respectively) (4) significantly higher mean basal TSH, and increased TSH response to TRH. We found a significant correlation between proteinemia and T4 or FT4 (p less than 0,001; p less than 0,01 respectively). In summary, our study: Shows that the low Total T4 observed in the Nephrotic Syndrome is not only due to a decreased protein bound T4, but also to a decreased FT4; And brings evidence for mild hypothyroidism in nephrotic patients.     

Familial nephrotic syndrome

Systematic pedigree information was obtained from 70 patients with idiopathic nephrotic syndrome; 16 patients were found to have familial nephrotic syndrome including 1 pair of affected monozygotic twins, 5 affected sibling pairs, 2 affected first cousins from a consanguineous family and 2 patients with sporadic cases from consanguineous families.Patients with familial and sporadic forms of the disease were compared by applying both clinical and histopathologic criteria. No significant differences were found between these groups, but both had a preponderance of males.In contrast to previous reports, the clinical course in the affected monozygotic twins was quite different, providing evidence for the importance of environmental influences on the course of this disease. Furthermore, in affected relatives neither the clinical course nor histopathologic classification was necessarily similar.The recurrence risk for siblings of patients with idiopathic nephrotic syndrome was 0.06. Several possible modes of inheritance were considered. Segregation analysis permitted the exclusion of simple recessive inheritance. The invariable concordance for the occurrence of nephrotic syndrome in both members of monozygotic twinships as well as the sex ratio renders a mixed model, with a small proportion of high risk recessive cases, equally unlikely. The available data are most consistent with a polygenic model which assumes a continuous distribution of disease liability with a discreet threshold effect.     

The nephrotic syndrome

The nephrotic syndrome is characterized by albuminuria, edema, hypoalbuminemia and hypercholesterolemia; frequently, it is accompanied by a depression of the basal metabolic rate. It occurs most often in the course of chronic glomerulonephritis but may exist independently, as in lipoid nephrosis. Rarely, it is associated with secondary syphilis, leptospiral infections, amyloid disease, Kimmelstiel-Wilson syndrome or nephrotoxic poisons.The term “nephrosis” was originally applied by Müller to degenerative lesions of the kidney primarily involving the renal tubules. The nephrotic state, however, occurs also with inflammatory diseases of the kidney. Furthermore, the significance of the tubular lesion in the etiology of the syndrome is open to question for it has been quite clearly shown that, in some instances at least, the tubular change may be the result and not the cause of albuminuria. It is obvious that some disturbance of the glomerular filter or in the serum proteins must be predicated to allow for the increased supply of protein presented to the tubules.It was originally suggested by Epstein that the low serum albumin in the nephrotic state might result solely from urinary loss of serum proteins and that edema formation could be adequately explained on the basis of the Starling hypothesis of lowered osmotic pressure in hypoalbuminemia. But there is evidence that the Epstein hypothesis does not afford a complete explanation for the formation of edema. Thus diuresis may occur spontaneously without any increase in the low serum albumin levels. Excess protein intake usually does not restore the blood level of albumin even when positive nitrogen balance is established and body protein is stored.It is now plain that leakage of albumin through the kidneys does not alone explain the manifestations of the nephrotic state, which evidently involves much more profound metabolic disturbances. Other factors evidently are at work. There is a renal defeet in the handling of the sodium ion by the kidnev. Adrenal cortical hormones conceivably might play a part in water and sodium balance; and the role of the anti-diuretic hormone of the posterior pituitary gland has yet to be properly evaluated. The significance of hypercholcsterolcmia and lowered basal metabolic rate in the nephrotic state is not known, nor is it understood why the alpha globulins apparently are increased and the gamma globulins decreased in the blood.Measures directed against the clinical abnormalities present in the nephrotic syndrome include diet high enough in protein to assure nitrogen balance; excessive feeding of protein accomplishes nothing more than restoration of body protein and may actually injure the renal tubules, Sodium intake is kept to less than 0.5 Gm. daily because more tends to promote edema. At this level, water may be taken freely; otherwise it. too, should be restricted. Of the diuretics, urea and mercurials are most often effective, but neither can be relied upon. Efforts to promote diuresis by increasing the osmotic pressure of the circulating plasma have been unsatisfactory. Therapy with hypertonic glucose, acacia, human plasma or serum fall into this category. Salt-tree for human albumin may be highly effective hut has serious limitations. Thyroid extract rarely produces diuresis. In children, intercurrent infections, particularly pneumococcic peritonitis, respond promptly to penicillin. Syphilitic nephrosis also yields rapidly to treatment with penicillin.Prognosis depends on the underlying disease. In lipoid nephrosis and chronic glomerulonephritis the duration of the nephrotic state cannot be predicted. In the former, however, the outcome is almost uniformlv good today since formerly fatal infectious complications may now be adequately handled. Patients in the nephrotic phase of chronic glomerulonephritis. however, (and these comprise by far the largest proportion of cases) still face the ultimate fate of patients with the underlying disease.     

Cytomegalovirus nephrotic syndrome

The case of a 5 months old infant with a nephrotic syndrome after neonatal cytomegalovirus infection is reported. Genomic amplification nested-PCR for CMV was positive in renal biopsy. Treatment with gancyclovir was effective to maintain nephrotic syndrome remission. We stresses the importance to discharge an infections cause of the nephrotic syndrome of newborns and infants due to the possibility on curative treatment.     

脂蛋白脂酶与代谢综合征

脂蛋白脂酶是脂质代谢的关键酶,主要水解甘油三酯,在乳糜微粒及极低密度脂蛋白的代谢中发挥重要作用.该酶的缺乏或活力异常,将导致糖、脂代谢紊乱.代谢综合征(MS)是以腹型肥胖,高血压,糖、脂代谢异常等多重心血管危险因素聚集为特征的临床综合征.越来越多的动物及临床证据表明,脂蛋白脂酶参与了 MS的发生、发展,故脂蛋白脂酶的研...