Jacques J. Bourgoignie

Glomerular Lesions in the Acquired Immunodeficiency Syndrome

Between January 1982 and December 1983, 75 patients with the acquired immunodeficiency syndrome were identified in our hospitals: 35% used intravenous drugs, 50% had proteinuria in excess of 0.5 g/dL, and 10% were nephrotic. Glomerular changes seen at autopsy in 36 patients included frequent mesangial lesions and deposits associated with mild asymptomatic proteinuria. Focal and segmental glomerular sclerosis was found in 5 patients and 4 of these had the nephrotic syndrome. Whereas reversible episodes of acute renal failure were not uncommon, terminal episodes of acute renal insufficiency occurred in 14 patients. The short survival of these patients may prevent the development of chronic renal failure.

The Clinical Spectrum of Renal Disease Associated With Human Immunodeficiency Virus

A nephrology consultation was called on 100 adult patients of 1,635 (6.1%) patients with human immunodeficiency virus (HIV) infection seen between 1982 and 1987 at the University of Miami/Jackson Memorial Medical Center. Renal disease was observed in all groups of patients with a risk factor for HIV infection with a lesser incidence, however, among homosexuals. Intravenous drug (IVD) use and possibly race appear to be important factors in the development of renal complications. Renal disease was the dominant clinical feature in eight asymptomatic HIV carriers and in 34 patients with AIDS-related complex (ARC) who had not developed the opportunistic infections and/or malignancies associated with acquired immunodeficiency syndrome (AIDS). Ninety-one percent of consultations were requested for evaluation of proteinuria and/or renal failure. Nephrotic range proteinuria, in excess of 3 g/24 h, was present in 52 patients, and was less prevalent in homosexuals than in other groups at risk. Renal failure (serum creatinine greater than or equal to 5 mg/dL), initially present in 32 patients, eventually developed in 69 and improved in only 18 of them. A renal biopsy, obtained for work-up of nephrotic syndrome (22 patients) or renal insufficiency (3 patients), uncovered a picture of focal and segmental glomerulosclerosis in all 25 instances. Overall, 76 patients are dead, seven are lost to follow-up, and 17 are alive, of whom eight (four HIV carriers, two patients with ARC, and two with AIDS) are on maintenance hemodialysis with a mean survival time of 217 days.

Reduction by Cimetidine of Serum Parathyroid Hormone Levels in Uremic Patients

Dietary restriction of phosphorus1 , 2 and administration of antacids3 have been shown to prevent or reverse uremic hyperparathyroidism, but patients find this therapy unpalatable and difficult to ...

Renal complications of human immunodeficiency virus type 1.

More than 87,000 patients with acquired immunodeficiency syndrome (AIDS) were reported to the Centers for Disease Control in the United States, of whom more than half died through January 1989. When the AIDS epidemic is considered worldwide, these numbers probably should be doubled (1). This review examines the electrolyte disorders and renal complications observed in patients with human immunodeficiency virus (HIV-1) (formerly called HTLV-III) infection.

Accuracy of Physical Examination in the Detection of Arteriovenous Fistula Stenosis

BACKGROUND AND OBJECTIVES Physical examination has been highlighted to detect vascular access stenosis; however, its accuracy in the identification of stenoses when compared with the gold standard (angiography) has not been validated in a systematic manner. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS A prospective study was conducted of 142 consecutive patients who were referred for an arteriovenous fistula dysfunction to examine the accuracy of physical examination in the detection of stenotic lesions when compared with angiography. The findings of a preprocedure physical examination and diagnosis were recorded and secured in a sealed envelope. Angiography from the feeding artery to the right atrium was then performed. The images were reviewed by an independent interventionalist who had expertise in endovascular dialysis access procedures and was blinded to the physical examination, and the diagnosis was rendered. Cohens kappa was used as a measurement of the level of agreement beyond chance between the diagnosis made by physical examination and angiography. RESULTS There was strong agreement between physical examination and angiography in the diagnosis of outflow (agreement 89.4%, kappa = 0.78) and inflow stenosis (agreement 79.6%, kappa = 0.55). The sensitivity and specificity for the outflow and inflow stenosis were 92 and 86% and 85 and 71%, respectively. There was strong agreement beyond chance regarding the diagnosis of coexisting inflow-outflow lesions between physical examination and angiography (agreement 79%, kappa = 0.54). CONCLUSIONS The findings of this study demonstrate that physical examination can accurately detect and localize stenoses in a great majority of arteriovenous fistulas.

A natriuretic factor in the serum of patients with chronic uremia

Sera from chronically uremic and normal individuals were subjected to gel filtration with Sephadex G-25 and the same fraction of both was infused into rats with a decreased nephron population to determine the effects on sodium excretion. Sodium excretion rate and fractional sodium excretion increased slightly with the normal fractions; but the increase in both functional parameters produced by the uremic fractions was substantially and significantly greater. The natriuresis could not be explained by associated changes in glomerular filtration rate (GFR), para-aminohippurate (PAH) clearance, filtration fraction, hematocrit, or blood pressure. The possibility thus exists that the inhibitor affected some component part of the transepithelial sodium transport system. The elution characteristics of the fraction plus certain of its physicochemical properties suggest that the inhibitor of sodium reabsorption by the rat nephron may be identical with the inhibitor of PAH uptake by kidney slices and the inhibitor of transepithelial sodium transport by the frog skin and toad bladder previously found in the serum of chronically uremic patients.

Functional Profile of the Isolated Uremic Nephron: ROLE OF COMPENSATORY HYPERTROPHY IN THE CONTROL OF FLUID REABSORPTION BY THE PROXIMAL STRAIGHT TUBULE

An in vitro approach to the study of single nephron function in uremia has been employed in evaluating the control of fluid reabsorption by the renal superficial proximal straight tubule (PST). Isolated segments of PSTs from the remnant kidneys of uremic rabbits (stage III) were perfused in vitro and their rate of fluid reabsorption compared with normal PSTs and with PSTs derived from the remnant kidneys of nonuremic rabbits (stage II). All segments were exposed to a peritubular bathing medium of both normal and uremic rabbit serum thereby permitting a differentiation to be made between adaptations in function which are intrinsic to the tubular epithelium and those which are dependent upon a uremic milieu.Compared with normal and stage II PSTs, there was significant hypertrophy of the stage III tubules as evidenced by an increase in length and internal diameter, and a twofold increase in the dry weight per unit length. Fluid reabsorption per unit length of tubule was 70% greater in stage III than in normal and stage II PSTs, and was closely correlated with the increase in dry weight. Substitutions between normal and uremic rabbit serum in the peritubular bathing medium did not affect fluid reabsorption significantly in any of the three groups of PSTs. Perfusion of the tubules with an ultrafiltrate of normal vs. uremic serum likewise failed to influence the rate of net fluid reabsorption. It has previously been observed that net fluid secretion may occur in nonperfused or stop-flow perfused normal rabbit PSTs exposed to human uremic serum. Additional studies were thus performed on normal and stage III PSTs to evaluate whether net secretion occurs in the presence of rabbit uremic serum. No evidence for net secretion was found. These studies demonstrate that fluid reabsorption is greatly increased in the superficial PST of the uremic remnant kidney and that this functional adaptation is closely correlated with compensatory hypertrophy of the segment. Humoral factors in the peritubular environment do not appear to be important mediators of the enhanced fluid reabsorption.

The Presence of a Natriuretic Factor in Urine of Patients with Chronic Uremia. THE ABSENCE OF THE FACTOR IN NEPHROTIC UREMIC PATIENTS

A gel filtration fraction of serum from chronically uremic patients has been shown previously to produce natriuresis in the rat. In the present studies, the same fraction from urine of uremic patients and normal subjects was studied for its natriuretic activity. Urine samples were obtained from 17 chronically uremic patients (mean glomerular filtration rate [GFR], 8.7 ml/min; mean fractional sodium excretion [FE(Na)], 5.7%), and 14 normal subjects. The fraction from the uremic patients produced a significant increase in absolute sodium excretion (U(Na)V) and FE(Na); the fraction from normal subjects had no statistically significant effect on either U(Na)V or FE(Na); and the difference between the response to the uremic vs. normal fractions was highly significant for both parameters of sodium excretion. When a more concentrated urine fraction from uremic patients was administered, a striking natriuresis was observed with values for FE(Na) rising to levels as high as 12%. Studies also were performed on eight patients with far advanced chronic renal insufficiency and the nephrotic syndrome. The serum fraction was studied in each of these patients and the urine fraction in three. For the group, U(Na)V in the assay rats decreased by 0.87 mueq/min and FE(Na) decreased by 1.35% after infusion of the serum fraction. These results differ significantly from those of patients with chronic uremia without the nephrotic syndrome. The data are consistent with the view that the increased activity of the natriuretic factor in the serum of chronically uremic patients is not due to failure of excretion; rather it relates either to an increased rate of production and/or a decreased rate of degradation. The data also show that the inhibitor is detectable when FE(Na) is increased, but not when uremia is associated with a sodium-retaining state.

Short-Term, High-Dose Pamidronate-Induced Acute Tubular Necrosis: The Postulated Mechanisms of Bisphosphonate Nephrotoxicity

A 76-year-old man had biopsy-proven acute tubular necrosis (ATN) after intravenous administration of 3 doses of 60 mg of pamidronate (Aredia) over a 2-week period. Pamidronate was given to treat hypercalcemia of unknown etiology. Other potential causes of acute renal failure were excluded with appropriate investigations. The patients preexisting renal impairment in the context of high-doses of pamidronate might have been a potentiating factor for nephrotoxicity. The ATN encountered in this patient resolved; however, short-term hemodialysis was needed. To the best of our knowledge, this is the first reported case of short-term, high-dose pamidronate-induced ATN in the absence of concomitant nephrotoxins. Although necrotic and apoptotic cell death after bisphosphonate administration has been seen in a variety of cells, the exact mechanism of nephrotoxicity is unknown. This report presents a case of pamidronate-induced ATN and discusses the potential mechanisms of bisphosphonate-induced nephrotoxicity.

Inhibition of transepithelial sodium transport in the frog skin by a low molecular weight fraction of uremic serum

An inhibitor of transepithelial sodium transport was found in a low molecular weight fraction obtained from serum of patients with far advanced chronic renal disease. In 18 nondialyzed patients, the mean inhibition of short circuit current (SCC) was 24.9 +/-2.2% (SE). With a comparable fraction from 11 normal subjects. SCC decreased by only 5.3 +/-1.5%. There was significantly greater inhibition with the serum fractions of patients with end stage renal disease being maintained on chronic hemodialysis than in the normal control group; but the degree of inhibition in the dialyzed population was significantly less than that observed in the nondialyzed chronically uremic patients. The inhibition of SCC produced by the serum fractions of a group of seven patients with acute renal failure was not significantly different from the control group despite the presence of high grade uremia in the former. The inhibitory fraction has characteristics identical with the uremic serum fraction which previously has been shown to inhibit p-aminohippurate (PAH) uptake by rabbit kidney cortical slices. With gel filtration through Sephadex G-25, the active fraction appears after the major peaks of substances as small as urea and sodium; hence it may have been retarded on the column. But its ultrafiltration characteristics suggest that its molecular weight may be less than 1000. The inhibitory capability was not destroyed by boiling, freezing, or digestion with chymotrypsin or pronase. Neither methylguanidine nor guanidinosuccinic acid in concentrations well above those present in the serum of uremic patients inhibited sodium transport in the frog skin. The data suggest that there is an inhibitor of sodium transport in the serum of patients with chronic uremia. The role of this material in the regulation of sodium excretion in uremia as well as its possible role as a uremic toxin are subjects of both theoretical and practical interest.