Clinical significance of the presence of cryoglobulins in patients with glomerulopathies not associated with systemic disease.

Serial serum samples from 102 children with glomerulopathies not associated with systemic diseases and from 23 normal controls were examined for the presence of cryoglobulins. Sera from controls, from patients with glomerulopathies thought to be mediated by immune complexes, and from those with non-immunologically mediated glomerulopathies demonstrated similar incidence of cryoglobulins. There was no correlation between cryoglobulin concentration or composition and the glomerular immunohistologic findings. Furthermore, persistence of cryoglobulinemia could not be correlated with progression of renal disease. Although cryoglobulins may contain immune complexes, determination of serum cryoglobulin concentration appears to be of little value in the diagnosis of immune complex mediated renal disease, nor in the assessment of disease activity or monitoring therapy in patients with glomerulopathies unassociated with systemic disease.

The significance of serial measurements of serum complement C3 and C4 components and DNA binding capacity in patients with lupus nephritis.

Eighteen patients with systemic lupus erythematosus (SLE) and proliferative glomerulonephritis, underwent serial serum determinations of C3, C4, and native DNA binding capacity, as well as repeat renal biopsy 7 to 48 months (median 25 months) following initial biopsy. Highly significant correlations were found between serum C3 levels and renal histologic changes (P less than 0.0001), and between serum C3 levels and DNA binding capacity (P less than 0.03). Histologic deterioration correlated with depressed C3 levels, while improvement was associated with normalization of C3 levels. No correlation between renal histologic changes and either serum C4 levels or DNA binding capacity was found. The data suggest that the serum level of C3 is the best index of activity of lupus nephritis.

Membranous nephropathy associated with multiple sclerosis.

Membranous nephropathy and multiple sclerosis are believed to be mediated by immune mechanisms. A patient is reported with the first described association of membranous nephropathy and multiple sclerosis. Its significance and possible pathogenetic mechanisms are discussed.

Indomethacin in the treatment of proximal tubular acidosis.

Treatment of a 7-week-old black male who had proximal tubular acidosis with large doses of bicarbonate did not achieve correction of the acidosis and was accompanied by diarrhea. Addition of indomethacin therapy (2 mg/kg/day) was followed by correction of the acidosis and allowed a decrease in the dosage of alkali.

Therapy of renal anemia in children and adolescents with recombinant human erythropoietin (rHuEPO).

Eleven anemic children and adolescents with a median age of 14 years (range six months-20 years) on chronic hemodialysis were treated with recombinant human erythropoietin (rHuEPO) intravenously three times a week for an average of 9.2 months. After eight weeks of therapy, hematocrit rose from 20.3 +/- 1.4% to 31.7 +/- 0.7% (0.20 +/- 0.01 to 0.31 +/- 0.007, p less than 0.001, mean +/- SEM). After reaching the target hematocrit of 30% to 33% (0.30 to 0.33), doses were adjusted individually. Blood transfusions were eliminated in all but one patient. All patients experienced an increase in appetite and energy level. Serum ferritin concentrations decreased in all patients who reached target hematocrit and seven required iron supplementation. Hypertension worsened in two patients and developed in two others. One patient's vascular access clotted. Dialysis efficiency and heparin requirements during dialysis did not change significantly. We conclude that rHuEPO is safe, effective, and should be recommended as treatment for anemia in children and adolescents on hemodialysis, but close monitoring for the development of hypertension and/or iron deficiency is necessary.

Urinary tract infections in children: effect of short course antibiotic therapy on recurrence rate in children with previous infections.

Eighty-five girls, ages 3-16, with a past history of recurrent urinary tract infections were treated for 10 days with either trimethoprim/sulfamethoxazole, ampicillin or cephalexin. Patients with normal roentgenograms as well as those with reflux and cortical scarring were included. In the 12 weeks following completion of treatment, a significantly lower recurrence rate was noted in children who received trimethoprim/sulfamethoxazole. There was no difference in the recurrence rate whether or not radiographic abnormalities were present. No serious side effects were noted with any drug regimen.

Cephalexin in the management of bacteriuria.

This report evaluates the effectiveness of cephalexin in the treatment of bacteriuria in 93 children. Cephalexin therapy eradicated sensitive organisms in 97 per cent of the cases regardless of recurrence, structural abnormality, or status of renal function. Nevertheless, recurrences with a new, resistant organism occurred significantly in certain patients, expecially those with major anatomic abnormalities, during a six-week follow-up period. The incidence of drug reactions was low.

A pathophysiologic basis for the diagnosis and treatment of the renal hypertensions.

Hypertension is a major medical problem with significant short- and long-term sequelae. Previous investigators have reported childhood hypertension to be secondary and when sexondary, renal. However, recent studies have shown primary (essential) hypertension to be more prevalent than secondary. Children with blood pressures at the 95th percentile for age deserve comprehensive evaluation and follow-up. Those with systemic evidence of side-effects will require therapy. Modern therapy should be based on pathophysiologic principles which include an understanding of volume-dependent and renin-dependent hypertension. The stepwise approach to therapy will produce the maximal therapeutic benefit.

Effect of lipoid nephrosis cytokine on glomerular sulfated compounds and albuminuria.

Supernatants from peripheral blood mononuclear cells cultures of 30 idiopathic, minimal lesion, nephrotic syndrome (IMLNS) patients in relapse and the same patients in remission were fractionated by gel filtration chromatography. Fractions eluting with carbonic anhydrase (29 kilodaltons) were infused for 5 days at the rate of 10 microliters/h into the left renal artery of Wistar rats using an Alzet osmotic pump. On the last day of infusion, rats were injected with 35sulfate (1.0 mCi/200 g) intraperitoneally and killed after 8 h. Glomeruli were isolated and glomerular basement membrane (GBM) obtained. There was a significant increase in 35sulfate uptake by GBM of the infused kidney (302 +/- 92 cpm/mg dry glomerular weight, mean +/- SEM) compared with the uptake seen in the contralateral kidney (157 +/- 36, P < 0.01) when the fraction from IMLNS patients in relapse was infused. No significant differences in 35sulfate incorporation were seen between infused kidney (166 +/- 41) and contralateral kidney (172 +/- 64) when the same fraction from patients in remission was administered. A significant increase in albuminuria was seen on the last day of infusion (14.2 +/- 1.0 mg/24 h, mean +/- SEM) when supernatant factor from IMLNS patients in relapse was used. No significant differences in urinary albumin excretion prior to and after infusion were seen when the same fraction from IMLNS patients in remission was administered. The in vivo infusion of supernatant factor from IMLNS patients in relapse increased the 35sulfate uptake by GBM and augmented albuminuria, suggesting that the factor may have pathogenic significance in the proteinuria of IMLNS.

A comparison of combinations of diuretics in nephrotic edema.

The metolazone-furosemide combination of diuretics was compared with the thiazide-furosemide combination in nephrotic patients with edema. Nine patients underwent a crossover, randomized study receiving furosemide (2 mg/kg per dose) and either metolazone (dose varied according to weight) or chlorothiazide (10 mg/kg per dose). An additive natriuretic and diuretic effect was observed after both metolazone and thiazide were combined with furosemide. The use of both types of diuretic combination was associated with marked kaliuresis. These combinations of diuretics seem equally effective in inducing natriuresis and diuresis in edematous nephrotic patients.

Effect of prednisone on nephrotic peripheral blood mononuclear cell mediated increase in 35sulfate uptake in rat glomerular basement membrane.

We have previously described a significant increase in 35sulfate uptake in rat glomerular basement membrane (GBM) when glomeruli were cocultured with peripheral blood mononuclear cells (PBMC) from patients with idiopathic minimal-lesion nephrotic syndrome (IMLNS) in relapse, but not with PBMC of IMLNS patients in remission. In the present study we examined the effect of prednisone therapy on the PBMC-mediated increase in 35sulfate GBM uptake. The GBM 35sulfate uptake after rat glomeruli were cocultured with PBMC from 11 IMLNS patients in relapse (geometric mean 437 cpm/mg dry glomerular weight) was significantly higher than the incorporation observed in glomeruli cultured alone (geometric mean 229 cpm/mg dry glomerular weight; p less than 0.01). However, no significant differences in 35sulfate uptake were seen between glomeruli cultured alone and glomeruli cocultured with PBMC from IMLNS patients when PBMC were obtained from the 11 patients on treatment with prednisone (2 mg/kg/day) or the same patients in remission and off prednisone therapy. Prednisone therapy abolished the PBMC-mediated increased 35sulfate uptake by rat GBM. GBM sulfated compounds seem to play a role in glomerular permeability. The temporal relationship between inhibition of GBM sulfate incorporation by prednisone and resolution of the proteinuria support the hypothesis that PBMC from IMLNS patients in relapse could secrete a lymphokine which by altering the metabolism of the GBM sulfated compounds may subsequently increase glomerular permeability to plasma proteins.

Circulating mediators of proteinuria in idiopathic minimal lesion nephrotic syndrome.

The pathogenesis of proteinuria in idiopathic minimal lesion nephrotic syndrome (IMLNS) remains to be elucidated. The most-accepted hypothesis is that the increased glomerular permeability to plasma proteins results from the effect of circulating factors on glomerular capillaries. This report critically reviews the current studies that have attempted to isolate and characterize this putative factor(s). Products released from hepatocyte or peripheral blood mononuclear cells or isolated by chromatography from serum or plasma have been tested in rats for their role in inducing proteinuria. These factors have been infused into the isolated kidney preparation or into the intact animal as a single venous injection, or continuously by pump for a period of 4 h to 7 days. Several of these isolated factors have been shown to induce proteinuria in rats. However, their exclusive pathogenetic role is questionable since none is always present in all IMLNS patients during relapse. Therefore, the increase in proteinuria in these patients may result from a single or a variety of factors as yet to be identified.

The effect of lymphocytes from renal transplant patients on glomerular basement membrane sulfate uptake.

We have studied the effect of peripheral blood mononuclear cells (PBMC) from renal transplant patients on 35sulfate uptake by rat glomerular basement membrane (GBM). Nine patients were included in the study; six were studied during an episode of acute allograft rejection and seven while not undergoing acute rejection. The sulfate uptake index, calculated as the ratio between uptake by GBM from rat glomeruli cocultured with PBMC and 35sulfate incorporation by GBM from glomeruli cultured alone, was significantly higher when glomeruli were cocultured with PBMC from patients undergoing an acute rejection (3.26 +/- 1.18, mean +/- SEM) than it when glomeruli were cocultured with PBMC from nonrejecting transplant patients not showing proteinuria (0.81 +/- 0.11) (P = 0.0053). After reversing the acute allograft rejection with resolution of proteinuria, the sulfate uptake index returned to normal in four of five patients. The fifth patient had persistent nephrotic syndrome and his sulfate uptake index remained elevated. These findings are similar to those observed in idiopathic minimal lesion nephrotic syndrome patients in relapse. Because the GBM sulfated compounds may play a role in glomerular permeability to plasma proteins, by acting on these compounds PBMC may be a common mechanism for proteinuria.

Effect of concanavalin A on nephrotic peripheral blood mononuclear cells mediated increased 35sulfate uptake in rat glomerular basement membrane.

We have previously shown a significant increase in 35sulfate uptake in rat glomerular basement membrane (GBM) when glomeruli were cocultured with peripheral blood mononuclear cells (PBMC) from patients with idiopathic minimal lesion nephrotic syndrome (IMLNS) in relapse, but an uptake not different than normal controls if glomeruli were incubated with PBMC of patients in remission. In the present study we examined 35sulfate uptake by GBM after PBMC from 12 IMLNS patients in remission were stimulated with Concanavalin A (Con A) (10 micrograms/ml of culture media). There was a significant increase in 35sulfate GBM uptake when glomeruli were cocultured with Con A-stimulated IMLNS PBMC (geometric mean), 331 cpm/mg dry glomerular weight) as compared to glomeruli cocultured with IMLNS PBMC (geometric mean, 200) (p = 0.048); glomeruli alone stimulated with Con A (geometric mean, 182) (p = 0.008) or glomeruli alone (geometric mean, 146) (p = 0.002). No significant differences were seen between the groups when glomeruli were cocultured with PBMC from 12 normal adults. These data show that Con A stimulated PBMC from IMLNS patients in remission alter the sulfate metabolism of rat GBM. The stimulation of PBMC with Con A reproduces the increase in 35sulfate uptake observed when glomeruli are cocultured with PBMC from IMLNS in relapse. Sulfated compounds in the GBM may play a role in glomerular permeability. Since stimulated nephrotic PBMC alter the metabolism of GBM sulfated compounds, these findings may have pathogenic significance.

Medical sequelae of reflux nephropathy.

RN represents a significant cause of chronic renal failure. Once established, the entity seems to follow a progressive course, regardless of therapeutic modalities. The association of glomerular lesions and hypertension may exacerbate the deterioration of renal function. Since, in humans, RN is almost always associated with urinary tract infections, treatment and prevention of infections is of paramount importance.