IgA nephropathy: multivariate statistical analysis aimed at predicting outcome.

BACKGROUND: Several risk factors of IgA nephropathy (IgAN) have been identified, but their importance in predicting outcome is still controversial. METHODS: We conducted a retrospective study on 119 patients (pts) with IgAN. All had a follow-up of over five years (mean 134+/-56 months). For each patient we recorded age, 24h proteinuria, hematuria, renal function (RF), arterial hypertension (AH) and histological features. Multivariate analysis was done for predictive purposes (segmentation, using Chi-squared Automatic Interaction Detection-CHAID). RESULTS: AH at the time of renal biopsy was the principal and independent predicting factor: 30/50 (60%) hypertensive pts had serum creatinine > or =1.5 mg/dL at the end of follow-up compared to 9/69 (13%) pts with normal blood pressure. Age was a further predictive parameter: 21/28 (75%) pts with AH and age over 39 years had reduced RF at the last examination. In this subgroup, 18/19 (95%) with evidence of tubulo-interstitial lesions showed a decline of RF. CONCLUSIONS: AH and age alone are significant prognostic factors; tubulo-interstitial lesions are an additional pointer to poor outcome in these pts. The algorithm obtained with segmentation analysis may be a guideline for prognosis in single patients with IgA nephropathy.

IgA nephropathy in cystic fibrosis.

The kidney does not usually present specific lesions in cystic fibrosis (CF), although in recent years renal involvement has been reported, particularly amyloidosis and immune complex glomerulonephritis. IgA nephropathy is rare. We report four cases of IgA nephropathy out of five renal biopsies performed in the last three years in patients with CF and renal involvement and discuss the possibility of a relationship between IgA nephropathy and CF.

Eicosanoid synthesis in peripheral blood monocytes: a marker of disease activity in lupus nephritis.

A typical feature of lupus nephritis is glomerular and interstitial leukocyte infiltration. In search of a serological marker of renal disease activity, we examined prostaglandin endoperoxide synthetase (PGHS) activity in peripheral-blood monocytes isolated from 5 healthy subjects and 11 untreated patients with biopsy-proven lupus nephritis, using radioimmunoassay of prostaglandin E2 (PGE2) and thromboxane B2 (TxB2) released during 24-hour cultures with selective stimuli/inhibitors. Unstimulated basal PGE2 and TxB2 synthesis, reflecting in vivo PGHS activity, was greater in the five patients with active renal involvement (World Health Organization [WHO] classes IVb-c) and the six lupus patients without active disease than in the five healthy subjects (TxB2, 2,643+/-198 [standard error], 2,015+/-190, 1,548+/-295 pg/10(6) cells, respectively). Escherichia coli lipopolysaccharide (LPS; 10 microg/mL) potently induced TxB2 or PGE2 synthesis in healthy controls (+255%+/-76% and +611%+/-190%, +688%+/-234% and +3,189%+/-154%; 4 to 24 hours, respectively), an effect abolished by 5 micromol/L of dexamethasone (DEX) or by 5 micromol/L of the protein synthesis inhibitor cycloheximide (CHX). Responses to LPS were reduced in lupus patients without disease activity and reduced even further in those with active nephritis. This may be related to substrate depletion or feedback functional inhibition of the inducible isoform of PGHS. Our assay may prove useful in the early detection of kidney disease activity in lupus erythematosus.

Atmospheric pollution originating from the interaction of different gaseous effluents.

During the last few years, several episodes of atmospheric pollution have been reported in a limited area near Guidonia, Rome. The area contains a disposal plant, Inviolata, for the collection of municipal solid waste (MSW) and a famous thermal water resort, the Acque Albule spring, which is a source of water rich in H2S. We conducted a multiparametric study in the areas surrounding the solid waste disposal plant and the Acque Albule spring. The concentration of main gaseous effluent was continuously monitored over a period of 4 months and the data relating to the meteorologic conditions in the area during the last few decades were examined. Our results suggest that most of the atmospheric pollution is due to the interaction of different gaseous effluents. Specifically, the presence of relatively high levels of hydrogen sulfide in the atmosphere, constantly released in large amounts by the Acque Albule springs, and of biogases (mainly hydrocarbons) from the organic matter present in the solid waste continuously unloaded and stored at the disposal plant, lead to mixing and photochemical interactions between these chemical compounds, which in turn are responsible for most of the polluting effects. Such interactions are promoted by the strong solar irradiation in the area that is enhanced by the peculiar local meteorological features that do not allow the pollutants to disperse.

Beta-thalassemia mutations in Rome. A high frequency of the IVSII-745 allele in subjects of latium origin.

We studied the molecular bases of beta-thalassemia in Rome, a city centrally located in Latium, which is a region with a low incidence of beta-carriers. People also come to Rome from other regions for specific or prenatal diagnostic assessment. Only 11 patients (20%) out of 62 characterized beta-thalassemia subjects were of Latium family origin. They presented five mutations with an uncommonly high frequency of the IVSII-745 allele, that was found in homozygosis in 4 unrelated patients from a southeastern area in the province of Frosinone. These data may indicate a founder effect.

[Nicardipine, alone or in combination with enalapril, in the therapy of arterial hypertension secondary to chronic nephropathy]. / La nicardipina, da sola o in associazione con l'enalapril, nella terapia dell'ipertensione arteriosa secondaria a nefropatia cronica.

The aim of the study was to evaluate the long term antihypertensive effect of nicardipine in hypertensive patients with chronic renal disease. Eight patients (creatinine clearance ranging from 51 to 78 ml/min/1.73 m2) received nicardipine (20 mg t.i.d.). Four weeks later, patients with diastolic blood pressure greater than or equal to 90 mmHg in recumbent position, were given enalapril (10 mg/day) as well. Blood pressure control was achieved in 3 patients treated with nicardipine alone and in 5 patients on a combined nicardipine-enalapril regimen, and it was maintained throughout the whole trial period (52 weeks). In two cases serum creatinine rose from 2.3 to 3.3 and from 1.4 to 2.2 respectively. However, the slope of the creatinine ratio, plotted against time, showed a significant reduction in renal function loss as compared to expected values. In conclusion, nicardipine, alone or in combination with enalapril, is an effective and well tolerated drug for use in treatment of hypertension secondary to chronic renal disease.

Angiotensin converting enzyme inhibition delays the progression of chronic renal failure in hypertensive patients with immunoglobulin A nephropathy.

Ten hypertensive, non-nephrotic patients with immunoglobulin (IgA) nephropathy treated with conventional therapy (vasodilators, beta-blockers, diuretics) were observed for 21.4 +/- 9 months. Treatment was then changed to an angiotensin converting enzyme (ACE) inhibitor alone for an additional 22.6 +/- 9 months. The ACE inhibitor therapy was associated with a lower diastolic blood pressure and a slowing in the rate of decline in renal function, but no change in proteinuria.

[Echographic aspects of kidney diseases and comparisons with needle biopsy]. / Aspetti ecografici delle nefropatie mediche e confronti con agobiopsia.

A study of 38 patients who underwent renal biopsy was designed to correlate the sonographic features of the kidney with the histologic changes in various renal parenchymal diseases. This research was performed in order to determine if sonography could be useful in the diagnosis and differentiation of renal parenchymal diseases. The ultrasound examination was based on the evaluation of some codified parameters: renal dimension, parenchymal thickness, cortical echogenicity and medullary dimension. There was no correlation between the specific sonographic features and the type of renal medical disease. In 28 patients (74%) with clinical and histological signs, sonography showed morphostructural alterations of the kidney.

Improvement of renal function with selective thromboxane antagonism in lupus nephritis.

To test the hypothesis that the vasoconstrictor thromboxane A2 may affect renal hemodynamics in lupus nephritis, we examined the short-term effects of a selective thromboxane-receptor antagonist, BM 13,177, and of low-dose aspirin. In a randomized, double-blind, crossover study, 10 patients with biopsy-proved lupus nephritis were given a 48-hour continuous infusion of BM 13,177 or placebo. At base line, seven patients had markedly elevated urinary levels of thromboxane B2, the breakdown product of thromboxane A2. During the infusion of BM 13,177, the inulin clearance rate, which was 68 ml per minute per 1.73 m2 of body-surface area at base line, increased by an average of 24 percent (range, 12 to 47 percent; P less than 0.01). Para-aminohippurate clearance was increased to the same extent, with no change in the filtration fraction. The bleeding time doubled, indicating an occupancy of platelet thromboxane receptors of more than 95 percent. The hemodynamic changes were associated with a significant increase in sodium excretion from 76 to 118 mmol per day (P less than 0.01) but with no change in arterial blood pressure. In another study, 10 additional patients with lupus nephritis were randomly assigned to receive either placebo or 20 mg of aspirin twice daily for four weeks. The aspirin regimen produced a selective, cumulative inhibition of platelet cyclooxygenase activity and a doubling of bleeding time. However, there was no change in the inulin clearance rate and no change in urinary levels of thromboxane B2 or 6-keto-prostaglandin F1 alpha, which are indicators of renal synthesis of thromboxane A2 and prostacyclin, respectively. We conclude that in lupus nephritis, impairment of renal function is at least in part mediated hemodynamically and is reversible with a thromboxane antagonist. Platelets, however, are not a major source of thromboxane A2 synthesis and action within the kidney.

Effects of sulindac and ibuprofen in patients with chronic glomerular disease. Evidence for the dependence of renal function on prostacyclin.

We investigated whether the glomerular synthesis of prostacyclin modulates the renal blood flow and glomerular filtration rate in chronic glomerular disease. The urinary excretion of 6-keto-prostaglandin F1 alpha, a stable breakdown product of prostacyclin, was significantly (P less than 0.01) reduced in 20 women with chronic glomerular disease, as compared with 19 controls, whereas excretion of urinary prostaglandin E2 was unchanged. In 10 patients randomly assigned to one week of treatment with ibuprofen, excretion of urinary 6-keto-prostaglandin F1 alpha and prostaglandin E2 was reduced by 80 per cent, the level of serum creatinine was increased by 40 per cent, and creatinine and para-aminohippurate clearances were reduced by 28 and 35 per cent, respectively. The reduction of both clearances was inversely related (P less than 0.01) to the basal urinary excretion of 6-keto-prostaglandin F1 alpha but not of prostaglandin E2. No functional changes were detected in five healthy women, despite a similar suppression of renal prostacyclin synthesis by ibuprofen. In contrast, one week of treatment with sulindac did not affect renal prostacyclin synthesis or renal function in the other 10 patients, despite a marked inhibition of extrarenal cyclooxygenase activity. We conclude that in patients with mild impairment of renal function, the renal blood flow and glomerular filtration rate are critically dependent on prostacyclin production. In such patients sulindac may be a safe substitute for other nonsteroidal antiinflammatory drugs.

Levels of Ia-like antigen bearing lymphocytes in patients with solid primary tumors.

In patients with different types of solid tumors who had no detectable metastasis and had received no radio- and chemotherapy the levels of Ia-like antigen bearing lymphocytes was determined by indirect immunofluorescence staining of peripheral lymphocytes with xenoantisera to framework determinants of Ia-like antigens. The level of Ia-like antigen bearing lymphocytes was increased in patients with urinary bladder carcinoma, was decreased in patients with carcinoma of the gastrointestinal tract and was within normal ranges in patients with melanoma, carcinomas of the breast, lung and genital tract. In patients with carcinomas of the gastrointestinal tract as well as in patients with carcinoma of lung and genital tract the levels of T lymphocytes measured by rosetting with sheep red blood cells, was reduced while it was not different from normal in other groups of patients. Determination of the level of lymphocyte subpopulations may provide information about the immunocompetence status of patients with solid tumors.

Ultrastructure of cell-mediated immunity. I. Comparison between E and EA rosettes.

The ultrastructural comparison between E and EA rosettes showed that, in the former, the rosetting lymphocytes are mostly round in shape and their interaction with sheep erythrocytes only consists of limited areas of membrane contact, in the latter, rosetting lymphocytes are mostly in the shape of uropods and surrounding ox red cells show pseudopods protruding towards the lymphocyte and coming into contact with it.

Ultrastructure of lymphocyte-mediated cytotoxicity. I. Interaction between phytohaemagglutinin-stimulated human lymphocytes and chicken erythrocytes.

The ultrastructural appearances of the interaction between normal phytohaemagglutinin (PHA)-stimulated human lymphocytes and chicken red cells (ChRBC) were studied. Close contact between ChRBC and control non-stimulated lymphocytes was often observed indicating that this is a non-specific phenomenon. In mixtures of PHA-stimulated lymphocytes and ChRBC, time-dependent development of interdigitating pseudopods between the two cell types was observed which was not seen in controls. Their development followed the same time-course as release of 51Cr when the ChRBC were pre-labelled with this marker. The findings suggest a relationship between the morphorlogical changes observed and the destruction of the target cells (ChRBC).