A 59-year-old man was diagnosed as having constrictive pericarditis 17 months after a typical hydralazine-induced autoimmune syndrome. This late complication of hydralazine has been reported only once. Ten years later the patient was found to have anti-neutrophil cytoplasmic antibodies directed against myeloperoxidase.

Antibodies, Antineutrophil Cytoplasmic↗

PubMed1996

The renal response to exogenous insulin in non-insulin-dependent diabetes mellitus in relation to blood pressure and cardiovascular hormonal status.

BACKGROUND: Non-insulin-dependent diabetes mellitus (NIDDM) is characterized by insulin resistance hyperinsulinaemia and a high frequency of hypertension. It has recently been shown that insulin exerts a sodium-retaining effect, which is preserved in NIDDM: We sought to determine whether insulin affected renal sodium handling differently in hypertensive and normotensive NIDDM patients. METHODS: After a baseline period of 2 h, eight normotensive (N-) NIDDM patients and eight NIDDM patients with hypertension (H-) underwent a euglycaemic clamp with infusion of two sequential doses of insulin (50 and 500 mU/kg/h) or vehicle (time control) during 2-h periods each. Fractional clearances of sodium and lithium were determined according to standard methods. Fractional lithium clearance was used to assess segmental tubular sodium handling. RESULTS: Insulin induced similar decrements in fractional sodium excretion (N-NIDDM: 43+/-5.9 and 57+/-9.1%,H-N IDDM: 48+/-16.4 and 62+/-12.5%, low and high insulin dose respectively). Distal tubular sodium absorption increased simultaneously. A fall in fractional proximal sodium reabsorption was observed in N-NIDDM (4.4+/-2.7 and 29.8+/-5.1%, low and high insulin dose respectively), which was attenuated in H-NIDDM (-5.0+/-7.3 and -2.1+/-13.9% respectively). The latter appeared to be related to a defective atrial natriuretic factor (ANF) and renal cyclic GMP response. A modest decrease in blood pressure occurred during insulin infusion that was not related to changes in ANF or FeLi. CONCLUSIONS: The findings suggest that insulin-induced sodium retention may contribute to hypertension in NIDDM if the homeostatic response to offset this effect fails.

Atrial Natriuretic Factor↗

PubMed1996

Respiratory failure in ANCA-associated vasculitis.

OBJECTIVE: To assess the prevalence, clinical manifestations, and course of respiratory failure in all patients who tested positive for antineutrophil cytoplasmic autoantibodies (ANCA) in our clinics in the period between January 1985 and January 1993. DESIGN: Case-series analysis. SETTING: Three teaching hospitals in the Netherlands. PATIENTS: Two hundred twenty consecutive patients suspected of having vasculitis and/or glomerulonephritis who tested positive for ANCA by indirect immunofluorescence and enzyme-linked immunosorbent assay. RESULTS: Sixty-two patients had pulmonary involvement. Acute respiratory failure developed in nine. Respiratory failure was related to infections in two of them and to ANCA-associated vasculitis in seven. These seven patients uniformly presented with pulmonary hemorrhage and diffuse pulmonary infiltrates. The diagnosis of systemic vasculitis was supported by the presence of a pulmonary-renal syndrome in all patients, and by detection of antibodies to the proteinase 3 or myeloperoxidase antigen in all but one patient. Antiglomerular basement membrane antibodies were absent. The mortality was high due to hypoxic respiratory failure, pulmonary superinfections, and concomitant renal failure. CONCLUSIONS: Acute respiratory failure due to vasculitis developed in one of every nine patients with ANCA-associated pulmonary disease. Patients usually present with pulmonary infiltrates and hemoptysis. A diagnosis of vasculitis may be further supported by analysis of the urinary sediment and determination of the ANCA target antigen. It remains to be proved that early detection of ANCA favorably affects the outcome.

Adult↗

PubMed1995

Differences between anti-myeloperoxidase- and anti-proteinase 3-associated renal disease.

We performed a retrospective study of the clinical features, the pattern of the pre-treatment renal function loss, the renal morphology and the outcome in 92 patients with anti-neutrophil cytoplasmic autoantibodies directed against proteinase 3 (aPR3; N = 46) or myeloperoxidase (aMPO; N = 46). Patients with aMPO had a higher median age than patients with a PR3 (63 and 56 years; P < 0.05). The mean (+/- SD) number of affected organs in the aPR3 group exceeded that of the aMPO group (3.9 +/- 1.4 and 2.2 +/- 1.1; P < 0.01). The prevalence of renal involvement did not differ between patients with aPR3 and aMPO (83% and 67%, respectively; NS). Pre-treatment renal function deteriorated significantly faster in aPR3- than in aMPO-associated renal disease. The kidney biopsies from patients with aPR3 showed a higher activity index (10.2 +/- 3.8 and 7.3 +/- 3.2; P < 0.03) and a lower chronicity index (4.5 +/- 2.6 and 7.0 +/- 3.1; P < 0.02) than biopsies from patients with aMPO. The kidney survival at two years was 73% in patients with aPR3- and 61% in patients with aMPO-associated renal disease (NS). We conclude that renal function generally deteriorates faster in aPR3- than in aMPO-associated renal disease. This goes together with more active renal lesions in patients with aPR3 and more chronic renal lesions in patients with aMPO. Despite these differences, there is no difference in outcomes between both antibody groups.

Adult↗

PubMed1995

Xanthogranulomatous pyelonephritis.

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Female↗

PubMed1995

Constant infusion clearance is an inappropriate method for accurate assessment of an impaired glomerular filtration rate.

Recently renewed interest has been focused on constant infusion clearance to assess GFR accurately. In this study we compared GFR and ERPF calculated from the constant infusion method (CIM = I x V/P) with that calculated from the standard method (StM = U x V/P), in 100 patients with renal disease who were subdivided in four groups according to their GFR-StM (< 30; 30-60; 60-90; > 90 ml/min). After a priming dose, a constant infusion of 125I-iothalamate (= GFR) and 131I-hippurate (= ERPF) was started at 9 a.m. The infusion rates were individually adjusted to the GFR which was approximated from the serum creatinine concentration. After a 90-min equilibration period, GFR-StM and ERPF-StM were determined for two 2-h periods. These values were compared with GFR-CIM and ERPF-CIM calculated from the plasma concentration of the respective tracers at the end of each 2-h period (= 210 and 330 min). In the patient group with GFR-StM < 30 ml/min, the 125I-iothalamate plasma concentration increased progressively over time. Consequently, average GFR-CIM at 210 min (34.2, SE +/- 2.1 ml/min) was higher than the GFR-CIM at 330 min (31.9, SE +/- 2.0 ml/min; P < 0.001). In addition both values were significantly higher than the corresponding GFR-StM values (18.1 +/- 2.4 and 15.3 +/- 1.6 ml/min respectively). In the two patient groups with GFR-StM > 60 ml/min, the 125I-iothalamate plasma concentration decreased progressively over time.(ABSTRACT TRUNCATED AT 250 WORDS)

Glomerular Filtration Rate↗

PubMed1994

Von Willebrand factor in the rat kidney: its localization and the effects of its in vivo interaction with specific antibodies.

Antiendothelial cell antibodies and increased von Willebrand factor (vWF) levels are observed in many renal diseases. We studied renal morphology after administration of rabbit anti-human factor VIII-von Willebrand factor (FVIII-vWFc) gamma-globulin (IgG) in rats. Isolated perfusion of normal rat kidney with the antibodies disclosed rabbit IgG along glomerular endothelium and in mesangial areas. Systemic administration resulted in an identical antibody distribution. C3 deposits and few electron dense deposits were transiently noted. After 1 week the mesangial deposition of rabbit IgG had increased significantly, most likely reflecting increased release of vWF by the endothelium. Thereafter, the deposits gradually relocated into mesangial stalk and into the glomerular vascular pole, and they had vanished after 6 weeks. Except for a mild influx of leukocytes, no renal injury occurred. In conclusion, although FVIII-vWFc antibodies cause mesangial immune deposits, antibodies against other endothelial antigens are apparently needed to inflict renal damage.

Animals↗

PubMed1994

A unique association of renal carcinoma with sarcoid reaction in the kidney.

Sarcoid reactions have been described in association with lymphomas and rarely with other solid tumors. We describe a patient with renal papillary adenocarcinoma and prominent sarcoid-like granulomatous infiltration of the ipsilateral and most likely the contralateral kidney. There was no evidence of extrarenal granulomas. This is the first description of impairment in renal function in a patient with renal carcinoma and with sarcoid reaction to this tumor isolated in the kidney.

Adenocarcinoma, Papillary↗

PubMed1994

The effect of SRI 63-675, a competitive platelet-activating factor receptor-antagonist, in the generalized Shwartzman reaction.

Evidence indicates a role for platelet-activating factor (PAF) in endotoxin (LPS)-induced shock. To determine its involvement in LPS-induced intravascular coagulation, we assessed the efficacy of SRI 63-675, a specific PAF receptor antagonist, to prevent fibrin deposition in the various organs of New Zealand White rabbits 4 h after two intravenous doses of LPS (100 micrograms/kg), spaced 24 h apart. SRI 63-675 significantly lowered peak tumor necrosis factor levels after LPS challenge. Administration of SRI 63-675 around either the first (150 mg/kg) or second LPS dose (120 mg/kg), however, did not prevent coagulation. The unexpected high mortality after combined administration of SRI 63-675 and LPS precluded assessment of PAF inhibition around both LPS doses on coagulation. Sole administration of SRI 63-675 induced rapid and transient changes in peripheral blood cell counts, and blood pressure and heart rate suggestive of intrinsic PAF-like activity. Although some other intrinsic toxic effect of SRI 63-675 cannot be ruled out, it is suggested that endotoxin may have primed the rabbit to the lethal, PAF-like, effects of SRI 63-675.

Animals↗

PubMed1994

Urinary epidermal growth factor excretion is correlated to renal function loss per se and not to the degree of diabetic renal failure.

Urinary epidermal growth factor (EGF) excretion is seen as a marker of tubular function, and some studies conclude that EGF excretion can already be reduced early in the development of diabetic renal disease. It is even suggested that EGF could play a role in kidney and glomerular enlargement and hypertrophy in diabetic subjects. We have investigated various groups of subjects, namely healthy controls (n = 5), patients with non-diabetic chronic renal insufficiency (n = 10), and normoalbuminuric (n = 9), microalbuminuric (n = 13) and nephropathic (n = 9) insulin-dependent diabetic subjects. In all subjects glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were measured using a continuous infusion of 125I-iothalamate and 131I-hippuran, respectively. Diabetic subjects were tested during (near) normoglycaemic conditions. During the renal function test urine was collected for EGF measurement (in ng). With lower GFR values, EGF excretion/min was also lower. GFR correlated well with EGF/min (r = 0.63, p < 0.001). Fractional EGF clearance (EGF/GFR) was comparable in all groups. There was no correlation between urinary albumin excretion rate and EGF excretion in the diabetic subjects (r = -0.18, n.s.) and in all subjects (r = -0.12, n.s.). There was a significant correlation between UAER and GFR (r = -0.51, p < 0.005). No significant correlation could be found between urinary albumin excretion rate (UAER) and EGF/GFR (r = -0.07, n.s.).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1993

Vasculitis and antineutrophil cytoplasmic autoantibodies associated with propylthiouracil therapy.

Vasculitis is a rare complication of propylthiouracil therapy. Antineutrophil cytoplasmic antibodies (ANCA) have been described in association with several vasculitic disorders. We report detection of ANCA against human neutrophil elastase, proteinase 3, and myeloperoxidase in serum from six patients who developed evidence of vasculitis during propylthiouracil treatment of hyperthyroidism. On withdrawal of the drug ANCA concentrations fell and clinical symptoms resolved completely.

Adult↗