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We describe the long-term follow-up of severe lupus nephritis treated with cyclophosphamide, with emphasis on the incidence of relapses after therapy withdrawal. From a cohort of SLE patients followed over a period of twelve years, we review the charts of the eleven with histologic evidence of class IV nephritis who reached complete remission with cyclophosphamide and who were followed for more than four years after the discontinuation. In all patients, cyclophosphamide was maintained for longer than two years after complete remission. Four patients relapsed following therapy withdrawal (36%). Sequential biopsies were taken in eight patients after remission or relapse and show a good histologic correlation with clinical renal data. Clinical remission with re-induction therapy could not be achieved in two patients after relapse. We conclude that relapse is frequently observed following cyclophosphamide withdrawal in lupus patients with diffuse proliferative glomerulonephritis initially responsive to this therapy. Studies are needed to determine the influence of different regimes of maintenance therapy on the rate of relapses.

We report a case of cystinuria with staghorn renal lithiasis in a solitary right kidney and chronic renal failure. Right nephropyelolithotomy was performed and although 29 renal calculi were extracted many stones remained in situ. A permanent nephrostomy was left in the kidney. Several months later the urine was infected chronically with a ureolytic Citrobacter freundii bacteria and urinary pH oscillated between 8.0 and 9.2. Spontaneous dissolution of the cystine calculi was observed and many tiny fragments of cystine were expulsed through the nephrostomy, following which renal function improved. Despite the conditions favoring struvite calculi, formation did not occur.

In May 1981, a massive intoxication of people who had ingested adulterated cooking oil took place in Madrid and nearby provinces. Although the patients presented, in the first phase of the disease, with acute respiratory illness, later on thromboembolic complications, severe neuromuscular involvement, and scleroderma-like cutaneous lesions appeared. Kidneys were apparently spared; however, 4 out of 842 admitted patients developed glomerulonephritis; kidney biopsies revealed glomerular, vascular, tubular, and interstitial changes. Cases 1 and 3 had diffuse proliferative endocapillary glomerulonephritis; case 2 had diffuse membranoproliferative glomerulonephritis; and case 4 had diffuse extracapillary glomerulonephritis. Three cases had vascular lesions characterized by degenerative and proliferative endothelial changes, intimal foamy macrophages, and partial or complete obliteration of the vascular lumen by concentric myxoid fibrosis. There were signs of necrosis of tubular epithelium along with edema and lymphocytic and eosinophilic interstitial infiltration. Two out of 22 autopsies had segmentary glomerulonephritis, and 17 out of 22 autopsies showed renal vascular lesions.

We studied the long-term effect of an angiotensin converting enzyme (ACE) inhibitor, captopril, on the progression of chronic renal failure and on the rate of urinary protein excretion. When compared with standard triple therapy, captopril slowed the progression of renal failure. Captopril was also able to reduce the proteinuria of non-diabetic glomerular origin. This reduction was not dependent on the presence or absence of arterial hypertension but was limited by the presence of low serum albumin levels, and only occurred in patients with proteinuria in excess of 3 g/24 h.

We have studied ten normotensive patients (nine male and one female, aged between 28 and 51 years) who each had a solitary functioning kidney and proteinuria. Six had undergone unilateral nephrectomy, and four unilateral renal agenesis. In each case, intravenous pyelography revealed only one functioning kidney with compensating hypertrophy. Mild to moderate chronic renal failure was present in six, and microhematuria in two. Proteinuria ranged from 1.10 to 4.10 g/24 hr, being in the nephrotic range in three patients. In seven patients, a renal biopsy showed focal glomerulosclerosis. Immunofluorescence studies demonstrated granular deposits of IgM in three and C3 in six cases, over the sclerotic areas. We suggest that the appearance of proteinuria and focal glomerulosclerosis in a patient with a solitary kidney could be due to chronic glomerular hyperfiltration.

Serum levels of vitamin A (VA) were measured in 71 hemodialysis (HD) patients and in 30 normal controls. 65 of the 71 patients were taking multivitamin preparations (MP) containing VA. The HD patients had significantly greater values: 7.81 +/- 2.86 mumol/l (224 +/- 82 micrograms/dl) versus 3.97 +/- 0.97 mumol/l (114 +/- 28 micrograms/dl; p less than 0.0005); those taking MP with large doses of VA showed the highest levels. Patients were divided as having normal (group I, n = 21) or elevated (group II, n = 50) serum levels of VA. Patients of group II had higher levels of serum calcium (Ca) and lower of serum phosphate (P) and PTH than those of group I. Four months after the withdrawal of oral VA, the serum levels of VA and Ca fell significantly in group II, while the serum P increased. On the contrary, in group I serum levels of VA, Ca and P remained unchanged. Serum triglycerides (TG) were significantly higher in group II but did not change after the withdrawal of VA. No differences between both groups of patients were observed for age, time on HD, residual diuresis, residual renal function, serum levels of cholesterol (CL) or anemia. A retrospective study of 18 hepatic biopsies of HD patients disclosed hyperplasia of Ito cells (VA-storaging cells) in 7 of them. These 7 biopsies belonged to patients who had taken large amounts of oral VA. Our data indicate that prolonged VA intake in HD patients is followed by an increase of serum CA, a decrease of serum P and PTH and a hepatic accumulation of VA.(ABSTRACT TRUNCATED AT 250 WORDS)

The hypothesis that abnormalities of immune function might occur in healthy first degree relatives of two patients with a familial IgA nephropathy was tested. After 7 days of culture, pokeweed mitogen stimulated peripheral blood mononuclear cells from the two affected members with IgA nephropathy (father and older son), as well as two other healthy sons, produced significantly more polymeric IgA than the controls. The fact that only the two patients with IgA nephropathy presented high serum levels of polymeric IgA favours the idea that a defect in the clearance of this immunoglobulin might be an important step in the appearance of this nephropathy. All the healthy members of the family had a normal OKT4+/OKT8+ cell ratio and a normal concanavalin A generated IgA suppressor cell function in contrast with the abnormalities observed in the two affected members and the previous results in a large number of patients with IgA nephropathy. These data suggest that the primary cellular abnormality might reside in B cells, being the T cell alterations observed in patients a secondary or subsequent phenomenon. These results further support the existence of genetic bases for the susceptibility to this disease.

The appearance of renal failure during episodes of macroscopic hematuria (EMH) in IgA nephropathy (IgAN) has been described as very unusual. The results of a prospective investigation on the effect of EMH on renal function in IgAN are presented. During a 3-year period, 29 episodes of EMH occurring in 21 patients with IgAN have been studied. A derangement of renal function (increase of serum creatinine by more than 0.5 mg/dl) was observed in 11 episodes (37.9%) with peak creatinine values ranging from 1.2 to 6.7 mg/dl. The worsening of renal function was accompanied by a longer duration of EMH (4.8 +/- 1.3 vs. 3.5 +/- 1.5 days; P less than 0.05) but not by arterial hypertension or edema. A complete recovery of renal function was observed in every patient 1 to 2 months after the start of EMH. The histological survey disclosed that the decrease of renal function correlated closely with the presence of red blood cell casts in as much as 50% of the tubular lumen and with findings of tubular necrosis. We conclude that a worsening of renal function can be observed frequently during the EMH. Tubular damage and obstruction by red blood cell casts may play a significant role in the pathogenesis of this complication.

The direct in vitro antigen-induced degranulation of rabbit basophils based on a simplified one-step method for the staining of these cells is reported. Degranulation was assessed by counting the number of basophils before and after exposure to antigen at 37 degrees C in the presence of Ca++. The degranulation was IgE-mediated, as shown by its passive transfer to nonimmunized rabbits by IgE-containing serum; also, the reaction was dependent on the presence of Ca++ ions and normal cell metabolism. The technique allowed the detection of serum factors capable of blocking the degranulation. It provided a means for following IgE sensitization at the cellular level, which is a better index of immediate hypersensitivity than the presence of circulating specific IgE.

The role of the basophils in acute serum sickness of rabbits was examined by monitoring daily the absolute number of basophils before, during and after the disease period. After antigen (bovine serum albumin, BSA) elimination, levels of serum IgE and in vitro basophil degranulation in the presence of BSA were determined. The results showed that the onset of glomerular lesions depends upon the simultaneous occurrence of circulating immune complexes greater than 19 S and of an in vivo basophil depletion--probably equivalent to degranulation--reaching 70% of the pre-disease number. Post-disease antigen-dependent in vitro degranulation of the basophils and levels of serum IgE anti BSA did not prove to be good indexes of basophil sensitization. Our data suggest that basophils are instrumental at early stages of the deposition of immune complexes, most probably through their sensitization by membrane-bound IgE antibodies.

From a series of 333 renal biopsies examined by immunofluorescence microscopy, 231 specimens corresponded to primary glomerulonephritis unassociated with systemic diseases. Of those 231 biopsies, 39 had diffuse mesangial deposits of IgA (16.8%). Thirty cases of IgA nephropathy had one to several glomeruli in the Epon-embedded tissue. All cases showed mild to moderate increase of mesangial cells and matrix. Mesangial deposits were present in all cases; subendothelial (5/30), intramembranous (3/30), and subepithelial (10/30) deposits wee also found. Occasional dense granular deposits involved the basement membrane of the capsule of Bowman (1/30) and the subendothelial region of some extraglomerular arterioles (2/30). Thinning (6/30) and splitting (4/30) of the glomerular lamina densa appeared focally in some cases.

We have prospectively studied 37 adult patients (15 males, 22 females; age 31 +/- 10.6 years) with previously undiagnosed isolated hematuria in which hypercalciuria or hyperuricosuria was found. Eighteen of them had had episodes of gross hematuria. Isolated hypercalciuria (4.4 to 10.4, X 5.6 +/- 1.9 mg/kg/24 hr) was found in nine patients (Group I), isolated hyperuricosuria (784 to 1500, X 1088 +/- 228 mg/24 hr) in 11 (Group II), and both hypercalciuria (4 to 8, X 4.9 +/- 1 mg/kg/24 hr) and hyperuricosuria (752 to 1476, X 1042 +/- 181 mg/24 hr) in 17 patients (Group III). Thiazide treatment for patients with hypercalciuria and allopurinol for those with hyperuricosuria were administered; calciuria and uricosuria became normal by the first month of therapy in every case. In 22 (59.4%) cases (Responder patients) hematuria resolved completely as soon as calciuria and uricosuria became normal. In the remaining 15 cases (Nonresponder patients) hematuria persisted despite the normal calcium and uric acid excretions. Several disorders that explained hematuria were diagnosed later in most of Nonresponder patients. Responder patients persisted without hematuria on the follow-up; only in three patients a transient relapse of hematuria was seen associated with a sudden increase of calciuria and uricosuria because of treatment withdrawal. There were no differences in age, male/female ratio nor in the basal values of calciuria and uricosuria between Responder and Nonresponder patients. A familial history of urolithiasis was found more frequently in Responder patients (64%) than in Nonresponders (20%) (P less than 0.05). We conclude that hypercalciuria and hyperuricosuria are definable and potentially reversible causes of hematuria in adult patients.