Long-term effect of lovastatin on lipoprotein profile in patients with primary nephrotic syndrome

Eight patients with biopsy-proven primary nephrotic syndrome were included in an open, prospective, two-year study of lovastatin. One patients was withdrawn after 6 months due to an asymptomatic rise in creatinine phosphokinase, which was rapidly reversed after interruption of lovastatin. In the remaining patients, treatment was well-tolerated and produced no side effects. After 2 years of treatment, these 7 patients had decreases in total cholesterol from 446 +/- 165 to 250 +/- 57 mg/dl (p < 0.001), LDL cholesterol from 343 +/- 121 to 174 +/- 49 mg/dl (p < 0.001), Apo B lipoprotein from 162 +/- 60 to 108 +/- 42 mg/dl (p < 0.05), triglycerides from 336 +/- 273 to 182 +/- 71 mg/dl (p < 0.04). There was no change in HDL cholesterol. The LDL/HDL cholesterol and the total/HDL cholesterol ratios fell from 15.0 +/- 12.1 and 19.1 +/- 17.2 mg/dl before the study to 4.4 +/- 1.2 and 6.3 +/- 1.6 mg/dl, respectively, at 2 years. A decrease in proteinuria from 8.6 +/- 4.6 to 5.0 +/- 3.7 g/24 h (p < 0.02) was noted in 4 patients on concomitant ACE inhibitor therapy. Renal function remained stable in all patients throughout the study, except for one whose moderate impairment progressed to end-stage renal failure requiring dialysis 3 months poststudy. We conclude that long-term lovastatin in patients with primary nephrotic syndrome is an effective and generally safe treatment for accompanying dyslipidemia.     

Hemostatic profile in nephrotic syndrome

OBJECTIVE: To evaluate the coagulation profile and its relation to steroid therapy, and the frequency of thromboembolic complications and its correlation with coagulation parameters in nephrotic syndrome (NS). SETTING: Hospital based. SUBJECTS AND METHODS: Forty children with NS were subdivided into four groups, namely, fresh cases, steroid dependent, remission after therapy and steroid resistant. An equal number of age and sex matched children served as controls. In all the study and control subjects, detailed clinical examination, liver function tests, renal function tests and detailed coagulation profile were done. Evaluation of renal veins and inferior vena cava for the presence of thrombosis was also done by abdominal ultrasonography. RESULTS: Thrombocytosis was detected in 57.5% and the degree of thrombocytosis was directly related to the amount of proteinuria. The mean prothrombin and thrombin times were within normal range in the study children. The activated partial thromboplastine time (APTT) was prolonged in six cases (15%) and three out of these six children had thromboembolic complications. Antithrombin-III level was significantly lower (p < 0.001) whereas protein C and S were significantly elevated (p < 0.001) as compared to controls. The levels became normal with remission of the disease. Steroid therapy significantly increased the levels of proteins C, protein S. AT-III and fibrinogen as compared to controls. Thromboembolic complications were seen in 3 cases (7.6%) and were associated with very low levels of AT-III and protein C and all three had serum albumin below 2 g/dl. CONCLUSIONS: The importance of coagulation profile in nephrotic syndrome is highlighted and a high index of suspicion for thromboembolic complications is warranted in patients with thrombocytosis, hyper fibrinogenemia, prolonged APTT and in children with low levels of AT-III, protein C and protein S.     

Mineralocorticoids in the nephrotic syndrome of children

Free aldosterone, the aldosterone precursor 18-OH-corticosterone, and 18-OH-deoxycorticosterone as well as the aldosterone metabolites 18-glucuronide and tetrahydroaldosterone were measured by radioimmunoassay in the urine of 24 children with the nephrotic syndrome. In addition renin activity, aldosterone and corticosterone were measured in plasma. All children with manifest edema showed increased values of one or more of the measured aldosterone parameters indicating hyperaldosteronism. In non-edematous patients one or more parameters were increased in 9 of 16 patients. Free aldosterone, tetrahydroaldosterone and 18-OH-corticosterone proved to be the most sensitive urinary parameters for the detection of increased mineralocorticoid function. Free urinary aldosterone was correlated with sodium excretion and with serum albumin. The pathogenesis of hyperaldosteronism in the nephrotic syndrome and its role in the development of edema are discussed.     

Strongyloidiasis associated with nephrotic syndrome

We report a nephrotic syndrome patient with eosinophilia who developed ileus, epigastralgia and malabsorption due to strongyloidiasis which became symptomatic by steroid therapy. The patient was then treated with thiabendazole and recovered. A percutaneous renal biopsy revealed minimal change nephrotic syndrome. This renal injury may be brought on by severe infection of Strongyloides stercoralis. It is important to rule out strongyloidiasis prior to corticosteroid therapy to patients from eosinophilia endemic areas.     

Lymphocyte ectoenzymes in childhood idiopathic nephrotic syndrome

Lymphocyte ectoenzymes with immunomodulatory function were investigated in 11 children with minimal change disease (MCD), 9 with primary focal segmental glomerulosclerosis (FSGS), and 17 age- and sex-matched healthy children. Basal, concanavalin A (Con A)-, and pokeweed mitogen (PWM)-stimulated lymphocyte ecto-5'-nucleotidase (5'-Nu), dipeptidyl peptidase IV (DPP IV), and alkaline phosphodiesterase I (APD) activities were determined. In MCD relapse ecto-APD activity of unstimulated lymphocytes was higher than controls. Ecto-APD of Con A-stimulated lymphocytes was below controls (23.0, range 7.2-48.7 nmol/min per 10(6) lymphocytes) in all active MCD (18.7, range 7.6-32.6), during corticosteroid treatment (14.6, range 4.5-54), and in remission (13.1, range 6.1-19.6), but was significant only in remission. Con A-stimulated DPP IV was significantly lower from controls (53.8, range 19.3-85.7 nmol/min per 10(6) lymphocytes) in all active MCD (38.1, range 10.8-82.1), during treatment (37.5, range 20.2-58.7), and in remission (39.4, range 24.3-69.6). In FSGS, unstimulated lymphocyte ecto-APD activity was greater than controls. However, Con A-stimulated lymphocyte ecto-APD and DPP IV activities were not significantly different from controls. Con A stimulation of lymphocyte ecto-APD and DPP IV activity was significantly reduced in MCD relapse and in remission, but not in FSGS. Basal, Con A-, and PWM-stimulated ecto-5'-Nu in MCD and FSGS were not different from controls. These results suggest a role for abnormal T cell function in MCD but not in FSGS. The difference in mitogen-stimulated expression of these ectoenzymes suggests a different pathogenesis of childhood MCD and primary FSGS.     

Acute renal failure in idiopathic nephrotic syndrome

The authors report a huge lymphangioma of the tongue in a sixty-seven years old female patient. The remarkable progression in dimensions of this lesion, leading to the inevitable protrusion of the tongue, led to the realization of an extended glossectomy, with a functional objective in mind. This simple procedure showed an excellent five years follow-up results. From this case report, the authors stress up on the etiopathogenic, pathological, clinical as well as therapeutic aspects of lingual lymphangioma.     

Iso-oncotic volume expansion in the nephrotic syndrome

1. In previous studies we found that albumin infusions caused only a modest natriuresis in the nephrotic syndrome, suggesting that hypovolaemia played no part in the sodium retention of these patients. However, this finding was inconclusive, since the hyperoncocity of the infused albumin probably opposed sodium excretion. 2. In the present study, we examined the effect of sustained (68 h) plasma volume expansion (+18%), by means of iso-oncotic albumin infusions, on renal function, blood pressure, humoral factors and sodium balance. 3. Plasma atrial natriuretic peptide levels increased almost threefold and renin-angiotensin system activity was suppressed. Glomerular filtration rate remained unchanged, whereas estimated renal plasma flow increased, resulting in a further decrease in filtration fraction. 4. The increase in plasma volume expansion was accompanied by a modest increase in sodium excretion, which, however, was less than the amount of sodium daily infused with the albumin solutions and consumed with the diet, so that net sodium was retained. 5. This observation supports the concept that an intrinsic renal defect causes the sodium retention in the nephrotic syndrome, and argues against the therapeutic use of albumin infusions.     

Urinary fibrin-fibrinogen degradation products in nephrotic syndrome

The urinary concentration of fibrin-fibrinogen degradation products (F.D.P.) was measured in 90 patients with proteinuria above 2 g/1 and correlated with proteinuria, differential protein clearances, serum urea and creatinine, and renal biopsy findings. There was a linear correlation (r equals 0-7; P less than 0-001) between the urinary F.D.P. excretion and the selectivity of the proteinuria such that patients with highly selective proteinuria excreted only small amounts of F.D.P. whereas those with non-selective proteinuria excreted much higher levels. There was a significant correlation between the urinary F.D.P. excretion and the urine:serum (U:S) ratio of IgG excretion but not with the U:S ratio or urinary excretion of albumin or transferrin. Sephadex G200 column chromatography of the concentrated urine in 26 cases showed that patients with highly selective proteinuria excreted predominantly F.D.P. of low molecular weight in the urine whereas those with non-selective proteinuria excreted mainly fibrinogen and products of high molecular weight. Hence the type and quantity of F.D.P. in the urine are determined primarily by the differential filtration of fibrinogen and the various degradation products from the plasma through the glomerular basement membrane, which in turn is determined by the "pore size" of the basement membrane. In clinical nephrology measurement of the urinary F.D.P. level provides a rapid and convenient means of estimating the differential protein clearance.     

Cyclophosphamide in the treatment of idiopathic nephrotic syndrome

Fifty-three patients 3 1/2 to 20 years of age with steroid-dependent idiopathic nephrotic syndrome (INS) were treated with cyclophosphamide and prednisone. Two dosage schedules were used: a short course (SC) at 3 to 5 mg/kg/day for six to eight weeks and a longer course (LC) at 3 to 5 mg/kg/day for eight weeks followed by 1.5 to 2.5 mg/kg for an additional four weeks. Prednisone was administered concurrently at 50 to 75 mg/sq M every other day. Twenty-nine patients were in the SC group and 24 in the LC group. The two groups did not differ significantly as to age at onset of idiopathic nephrosis nor as to the duration of the INS prior to cyclophosphamide therapy. All patients were followed for a minimum of 42 months after cyclophosphamide therapy. The SC was associated with a higher relapse rate during the first year than the LC (42% and 8% respectively, .01 larger than P less than .025). At 42 months 63% of the LC group were in remission compared with 21% in the SC group.     

Fatal hyperthrombotic condition complicating nephrotic syndrome

A twenty-year old woman was admitted to hospital with impaired consciousness and a left hemiparesis. A cerebral CAT-scanning was reported normal. Convulsions and respiratory insufficiency made intubation and mechanical ventilation necessary. Laboratory examination showed an extremely low concentration of albumin in plasma (109 microM) and gross albuminuria was present. No other signs of renal failure occurred. The patient deteriorated during three days and died with signs of cerebral incarceration, despite efforts to reduce intracranial pressure. Autopsy showed a large thrombus of the sagittal sinus as the presumed cause of death. No thrombus was found in the renal vein. The association between nephrotic syndrome and thrombosis is discussed.