Leonarda B. Sablay

The effect of normalization of serum complement and anti-DNA antibody on the course of lupus nephritis: a two year prospective study.

A prospective study was carried out in 25 patients with systemic lupus erythematosis (SLE) on the effect of normalizing serum complement (CH50) and anti-DNA antibodies on the course of lupus nephritis. In 16 of the 25 patients, CH50 was maintained within the normal range for two years. Urinary protein excretion increased or remained low in all 16. Repeat renal biopsies were performed in 10 of these 16, and disclosed either stabilization of glomerular disease or diminution. In the nine patients in whom CH50 could not be normalized with tolerated doses of drugs, urinary protein excretion increased or remained increased. Repeat renal biopsies in six of these nine patients were carried out and showed worsening of glomerular disease in five. No clear-cut correlation was found between urinary protein excretion or renal disease and the serum levels of anti-DNA antibody. We conclude from these observations that continuous normalization of CH50 by drug therapy in patients with SLE is associated with stabilization or diminution of lupus nephritis.

Effect of long-term normalization of serum complement levels on the course of lupus nephritis

PURPOSE We compared the long-term outcome of patients with lupus nephritis in whom normalization of complement levels (CH50) was sustained by adjustment of immunosuppressive therapy to those patients with persistently low complement levels despite similar immunosuppression in whom therapy was adjusted solely on the basis of clinical disease activity. PATIENTS AND METHODS Thirty-nine female patients with lupus nephritis recruited from 1972 to 1979 were prospectively studied (mean follow-up, 116.7 +/- 11 months). Entry criteria included initial renal biopsy, low CH50, and elevated anti-DNA antibody levels. A second biopsy was performed in 24 patients after an interval of 40.6 +/- 5 months. Treatment was started with prednisone (1 mg/kg/day). Azathioprine at a dose of 1.5 to 2.0 mg/kg/day was added if complement was not normalized by prednisone alone. Twenty-five of 39 patients had normal complement levels within six months (Group 1), and immunosuppressive therapy was tapered but continuously readjusted to the lowest dosage that preserved normal CH50 and maintained clinical remission. Eight of these 25 patients subsequently became persistently hypocomplementemic due to inadequate drug intake (Group 1B), whereas the complement levels continued to be controlled in the other 17 patients (Group 1A). Despite similar therapy, the remaining 14 patients did not achieve normalization of complement within the initial six months of therapy, and therefore future treatment decisions were based solely on clinical symptoms (Group 2). Renal pathologic lesions were classified according to World Health Organization criteria and a semi-quantitative chronicity index. RESULTS During the first six months, there were no significant differences in clinical or histologic features between patients in whom complement levels were controlled and patients in whom complement levels were not controlled. After a mean observation period of 10 years, however, patients with consistent normalization of complement (Group 1A) did much better than patients with only short-term complement control (Group 1B) or persistent hypocomplementemia (Group 2). Both groups with low complement levels had a similar outcome with significantly worse kidney and patient survival. Life-table analysis demonstrated that the differences in outcome between complement-controlled and complement-uncontrolled groups became apparent only after five or more years of follow-up. Patients with a low chronicity score on initial biopsy whose complement level was controlled did uniformly well with no renal failure or death. (ABSTRACT TRUNCATED AT 400 WORDS)

Combined antihypertensive and lipid-lowering therapy in experimental glomerulonephritis.

We examined the interrelation between systemic hypertension, hyperlipidemia, and progressive renal injury in experimental glomerulonephritis. Induction of nephrotoxic serum nephritis in Sprague-Dawley rats led to systemic hypertension and hyperlipidemia. Four groups of rats were studied over a 16-week period: (1) untreated nephritic rats; (2) nephritic rats treated with hydralazine, reserpine, and lasix (AH); (3) nephritic rats treated with lovastatin (4 mg/kg) (Lova); and (4) nephritic rats treated with combined antihypertensive/lipid-lowering therapy (AH/Lova). Systolic blood pressure rose progressively in untreated rats (152 +/- 4 mm Hg at 16 weeks). Blood pressure was reduced by antihypertensive therapy (P < .001) (108 +/- 2 mm Hg in the AH group and 111 +/- 3 mm Hg in the AH/Lova group) but remained elevated in animals treated with lovastatin alone (P > .05) (156 +/- 3 mm Hg in the Lova group). Serum cholesterol rose progressively in untreated rats (3.70 +/- 0.85 mmol/L [143 +/- 33 mg/dL] at 16 weeks). The rise in serum cholesterol was prevented by lovastatin therapy (P < .001) (2.22 +/- 0.41 mmol/L [86 +/- 16 mg/dL] in the Lova group and 2.09 +/- 0.52 mmol/L [81 +/- 2 mg/dL] in the AH/Lova group) but not antihypertensive therapy (P > .05) (2.92 +/- 0.65 mmol/L [113 +/- 25 mg/dL] in the AH group). Proteinuria was reduced by antihypertensive therapy (P < .001) and lipid-lowering therapy (P < .05) (16-week values: 1.069 +/- 0.167 g/d in untreated rats, 0.663 +/- 0.164 g/d in the Lova group, 0.392 +/- 0.051 g/d in the AH group, and 0.176 +/- 0.035 g/d in the AH/Lova group).(ABSTRACT TRUNCATED AT 250 WORDS)

Recurrent Membranoproliferative Glomerulonephritis Type 1 in Successive Renal Transplants

We report a man who developed renal failure due to membranoproliferative glomerulonephritis (MPGN) type 1 which recurred in two cadaveric kidney transplants. This is the third such case in the literature. Nephrotic syndrome developed within 1 month following transplantation and histologic evidence of disease recurrence was documented in both kidneys 2 months after transplantation. Both grafts failed within 18 months. Factors which determine disease recurrence remain obscure.

Adult Wilms Tumor Treated with Radiotherapy and Chemotherapy: A Case Report

A 24-year-old man underwent a left radical nephrectomy for a mass that was found to be a Wilms tumor. The postoperative course, consisting of combined radiotherapy and chemotherapy, is discussed and the recent literature is reviewed.

Recurrent Crescentic Membranous Nephropathy in Two Successive Renal Transplants: Association with Choroidal Effusions and Retinal Detachment

We report the case of a 50-year-old man in whom crescentic membranous nephropathy recurred in two succesive renal transplants leading rapidly to renal failure. Deterioration of renal function was associated with choroidal effusions and retinal detachments. Multiple serologic tests were negative. High-dose steroids, cyclophosphamide, cyclosporine, plasmapheresis and OKT3 failed to arrest the deterioration of renal function.

Superoxide dismutase: Enhanced small intestinal preservation

Injury from oxygen free radicals has been suggested to be of greater significance in the preservation of small intestine than of other organs. To determine if using the free radical scavenger, superoxide dismutase (SOD), with University of Wisconsin (UW) solution would improve preservation of small intestine, acute and chronic studies were conducted. Thirty-centimeter segments of small intestine from Lewis rats were flushed with and stored in Collins, UW, or SOD-modified (8000 U/ml) UW solution at 4 degrees C for 18 hr. For the acute study, small intestine segments were subsequently reperfused using support rats. The support rats in the UW/SOD group also received SOD (1750 U, iv) at the onset of reperfusion of small intestine. After 2 hr of reperfusion, maltose absorption and weight gain of small intestine were determined. For the chronic study, small intestine segments were transplanted as isografts. SOD (1750 U, iv) was also given to recipients prior to reperfusion of grafts in the UW/SOD group. Long-term effects were determined by recipient survival for at least 17 days. Results showed the small intestine in the UW/SOD group had the best recovery of mucosal absorption (256 +/- 39 versus 202 +/- 21 in the Collins group, P less than 0.01), the least percentage weight gain (19 +/- 3% versus 25 +/- 5% in the UW group and 38 +/- 5% in the Collins group, P less than 0.01), and the best 17-day survival rate (9/12 versus 2/9 in the UW group, P less than 0.025, and 0/8 in the Collins group, P less than 0.01) among the three groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of Dietary Electrolyte Supplementation on Gentamicin Nephrotoxicity

The effects of electrolyte supplementation via drinking solutions on gentamicin-induced nephrotoxicity were studied in rats. Four groups of animals were injected with gentamicin, 120 mg/kg daily for 5 days and were studied 2-4 days after the last injection. Electrolyte supplements were begun before the gentamicin injections and were continued throughout the study. The drinking solutions were tap water, NaCl, NaCl + KCl, or NaHCO3 + KHCO3 + diamox. At the end of the study, blood urea nitrogen (BUN) and serum creatinine were markedly increased only in the group receiving tap water. Nevertheless, 24 hour creatinine clearance in awake rats and inulin clearance in anesthetized rats were found to be severely reduced in all gentamicin-treated animals. However, the rats receiving NaHCO3 + KHCO3 + diamox had significantly higher creatinine clearance than all other experimental groups. Proximal intratubular free-flow pressure, measured by micropuncture, and internal proximal diameters were significantly increased above normal controls in all groups, but were least abnormal in the rats receiving HCO3- and diamox. Semiquantitative histologic evaluation revealed significantly less tubular necrosis and cast formation in this group than in all the other experimental groups. The observations suggest that dietary sodium, potassium, and chloride supplements, even accompanied by large fluid intake, provide relatively little protection against gentamicin nephrotoxicity. In contrast, HCO3- and diamox supplements resulted in significant, albeit incomplete, protection of GFR and renal histology.