Functional adaptation of nephrons in dogs with acute progressing to chronic experimental glomerulonephritis.

Although a diminished fractional excretion of sodium (FENa) is the hallmark of acute proliferative glomerulonephritis (APGN), an enhanced natriuresis per glomerular filtration rate (GFR) in the chronic phases of this disease has been reported. We studied this adaptive response utilizing two different split-bladder dog models with unilateral, and a third group of dogs with bilateral Masugi's nephritis. Group I. Six dogs with unilateral nonaccelerated APGN studied a mean of 6 days after induction had a mean base-line APGN/intact kidney GFR of 31/50 ml/min (P less than 0.005) and FENa of 0.2/0.75% (P less than 0.005). Acute volume expansion caused a smaller absolute increase in FENa from the APGN kidney, 1.6%, than from the intact kidney, 4.0%, (P less than 0.01). Maximum tubular secretion of rho-aminohippuric acid/GFR (TmPAH/GFR) measured in three dogs was higher in the APGN kidney than intact kidney, 13.1 vs. 9.3 mg/dl. Subsequent studies on three of the six dogs when the disease had become chronic demonstrated a reversal in the pattern of sodium excretion in response to volume expansion. Group II. Six dogs with accelerated unilateral APGN (dogs presensitized to antibody source) studied a mean of 5 days after induction had a mean base-line APGN/intact kidney GFR of 16/57 ml/min and FENa of 0.22/0.12% (P less than 0.1). Contrary to group I, volume expansion caused a greater absolute increase in FENa from the APGN kidney, 5.8%, than from the intact kidney, 2.9% (P less than 0.05). TmPAH/GFR studied in four dogs was similar for both kidneys, 17.9 and 18.5 mg/dl for the APGN kidney and intact kidney, respectively. Group III. Sequential studies were performed on seven dogs with bilateral nonaccelerated APGN. Initially each demonstrated sodium retention and a smaller absolute increase in FENa in response to volume expansion compared to a predisease control study. With disease progression, volume expansion induced a greater absolute increase in FENa than in the control study. We concluded that (a) the fractional excretion of sodium from the APGN kidney will be less or greater than the contralateral intact kidney or control study depending on the severity and/or chronicity of the disease, possibly as the result of morphologic alterations; (b) the degree of extracellular fluid volume expansion is an important variable influencing similarity of glomerulotubular balance between the APGN and contralateral intact kidney; and (c) the "intact nephron hypothesis" applies in a limited fashion to kidneys with APGN in the absence of volume expansion just as it does for kidneys with chronic glomerulonephritis or pyelonephritis.

Pseudomonas aeruginosa bacteremia in a dialysis unit. 11. Relationship to reuse of coils.

Blood for culture was obtained over a six week period from 17 patients undergoing long-term hemodialysis. Bacteremia was detected during 18 of 201 dialyses. Blood drawn during fifteen of these dialyses contained pseudomonas aeruginosa. Ten of the 17 patients (59 per cent) had a Pseudomonas bacteremia some time during the study. Only one patient was symptomatic. The frequency of positive cultures was related to reuse of coils. No cultures were positive until after the fifth use, but by the tenth use, 41 per cent of the dialyses were associated with bacteremia. All coils that were used repeatedly and 32 of 48 of those used only once, grew Ps. aeruginosa when filled with media and incubated. This suggests that the coils were inoculated during dialysis and that benzalkonium chloride, the sterilizing agent, was unable to eradicate this organism. With repeated uses, the number of residual bacteria in the coil became large enough to cause detectable bacteremia during dialysis.

Septic choroiditis with serous detachment of the retina in dogs.

The present study describes a model of multifocal septic choroiditis with serous retinal detachment after intracarotid injection of Staphylococcus aureus or Streptococcus faecalis. The fundus lesions occurred mainly in the tapetal area and, on ophthalmoscopic examination, were more extensive after S. aureus than after S. faecalis injection. On histopathologic examination there were microabscesses in the inner choroid and subretinal space, disrupting the outer retina but sparing the inner retina.

Standardized surveillance of hemodialysis vascular access infections: 18-month experience at an outpatient, multifacility hemodialysis center.

OBJECTIVE: To develop a standardized surveillance system for monitoring hemodialysis vascular-access infections in order to compare infection rates between outpatient sites and to assess the effectiveness of infection control interventions. DESIGN: Prospective descriptive analysis of incidence infection rates. SETTING: An outpatient hemodialysis center with facilities in Idaho and Oregon. PATIENTS: All outpatients receiving chronic outpatient hemodialysis. RESULTS: There were 38,096 hemodialysis sessions (31,603 via permanent fistulae or grafts, 5,060 via permanent tunneled central catheters, and 1,433 via temporary catheters) during an 18-month study period in 1997 to 1998. We identified 176 total infections, for a rate of 4.62/1,000 dialysis sessions (ds). Of the 176, 80 involved permanent fistulae or grafts (2.53/1,000 ds), 69 involved permanent tunneled central catheter infections (13.64/1,000 ds), and 27 involved temporary catheter infections (18.84/1,000 ds). There were 35 blood-stream infections (0.92/1,000 ds) and 10 episodes of clinical sepsis (0.26 /1,000 ds). One hundred thirty-one vascular-site infections without bacteremia were identified (3.44/1,000 ds), including 65 permanent fistulae or graft infections (2.06/1,000 ds), 42 permanent tunneled central catheter infections (8.3/1,000 ds), and 24 temporary catheter infections (16.75/1,000 ds). CONCLUSIONS: Infection rates were highest among temporary catheters and lowest among permanent native arteriovenous fistulae or synthetic grafts. This represents the first report of extensive incidence data on hemodialysis vascular access infections and represents a standardized surveillance and data-collection system that could be implemented in hemodialysis facilities to allow for reliable data comparison and benchmarking.

Immediate effect of nephrotoxic serum on kidney function in the dog.

Nephrotoxic anitbody rapidly fixes to glomerular basement membrane following systemic injection and immediately initiates histopathologic alterations. We studied the functional changes induced by nephrotoxic serum (NTS) in dogs starting 20 min after injection using three different protocols. By this time the GFR, UNa V and FENa had decreased in each study. Volume expansion resulted in a significantly smaller absolute increase in FENa than in the preinjection control study (1.1 vs. 2.8%, p less than 0.005), while maximum tubular secretion of PAH (TmPAH) and reabsorption of glucose (Tm glucose) stayed constant following NTS; thus TmPAH/GFR and Tm glucose/GFR increased significantly. These studies demonstrate that glomerular function is rapidly affected by NTS while absolute tubular function is relatively well maintained. Since histologic and functional changes occurred simultaneously, it seems likely that the functional changes were the direct consequence of the pathologic alterations.

Sodium transport in dogs with acute remnant and glomerulonephritic kidneys.

The nephron site responsible for the different patterns of sodium excretion in response to extracellular volume expansion observed in dogs with bilateral acute remnant kidneys, acute NTN, and normal kidneys was studied with clearance and micropuncture techniques. Mean kidney GFR's in the remnant and NTN kidneys were similar at 14 and 15 ml/min, respectively, compared to 28 ml/min for the normal kdineys. However, SNGFR's were normal in the remnant kidneys but markedly reduced in dogs with NTN. Mean absolute sodium excretion was similar for the remnant and normal kidneys both during the control phase and after volume expansion. Because of the reduced GFR, FENa of the remnant kidneys was significantly higher in each situation. In contrast, mean absolute sodium excretion was markedly less in dogs with NTN than in normal dogs both before and after volume expansion. Although FENa during the control phase was similar to that in normal dogs, it increased significantly less with volume expansion. Despite these differences in urinary sodium excretion, the percent sodium reabsorption at the end of the proximal convoluted tubule was similar in all three groups. In addition, volume expansion depressed proximal SFENa to the same degree in each group. Therefore the different patterns of urinary FENa were the result of differences in fractional sodium reabsorption by the nephron segments distal to the proximal convoluted tubule. Decreased distal delivery of sodium secondary to the reduced SNGFR also contributed to the decreased sodium excretion in acute NTN.

Acute effect of nephrotoxic serum on renal sodium transport in the dog.

In order to study the tubular mechanism for salt retention in acute proliferative glomerulonephritis, clearance and micropuncture experiments were performed on nine volume-expanded dogs before and after injection of sheep anti-dog glomerular basement membrane (GBM) antibodies (nephrotoxic sera [NTS]). Histologic sections obtained two hours after NTS injection following completion of the functional studies demonstrated infiltration of glomerular tufts by polymorphonuclear leukocytes, swelling of both glomerular endothelial and mesangial cells and the mesangial matrix, and linear anti-GBM antibody deposits along the glomerular capillaries. There was an almost immediate reduction in glomerular filtration rate (GFR), filtration fraction, urine flow and absolute and fractional sodium excretion; arterial blood pressure and renal plasma flow were not significantly altered. Micropuncture studies revealed no change in fractional sodium reabsorption in the proximal tubule despite a fall in single nephron GFR. A proportional reduction in single nephron and kidney GFR coupled with an unchanged intrarenal distribution of blood flow following NTS suggests a relatively uniform effect on both superficial and deep nephrons. In contrast to the well-preserved glomerulotubular balance in the proximal tubule, fractional distal sodium reabsorption was significantly increased as reflected by the decreased fractional urinary sodium excretion. We conclude that salt retention and low fractional urinary sodium excretion observed in acute glomerulonephritis could be primarily due to reduced distal delivery of sodium which leads to increased fractional sodium reabsorption in the nephron segments distal to the proximal convoluted tubule.

Glomerulonephritis with anti-glomerular basement membrane antibody during pregnancy: potential role of the placenta in amelioration of disease.

A case of rapidly progressive glomerulonephritis with glomerular deposition of anti-glomerular basement membrane (anti-GBM) antibody during pregnancy is described. Development of precipitous renal failure postpartum raised the possibility that the placenta may have served as an adsorptive surface for the autoantibody, thereby ameliorating its manifestations antepartum. Sera from the patient obtained during pregnancy contained low titers of anti-GBM immunoglobulin G. No antibody was identified in the serum from the healthy infant. Additional studies of this patient's sera, as well as sera from other patients with documented anti-GBM antibody-mediated glomerulonephritis, demonstrated that binding of anti-GBM antibody to placental membranes can occur, although it appears weaker than binding to basement membranes in renal glomeruli. We postulate that the patient's accelerated decline in renal function postpartum may have been due to removal of the ameliorating influence of the placenta.

Correction of protein binding defect in uremic sera by charcoal treatment.

Protein binding of numerous drugs, primarily organic acids, is decreased in sera from uremic patients. The defect in binding is (1) greater than can be accounted for by hypoalbuminemia alone; (2) unchanged by prolonged in vitro dialysis; (3) transferred in the protein but not the ultrafiltrate fraction of uremic serum; and (4) not reproduced by addition of low and middle molecular weight compounds known to accumulate in uremia. However, treatment with activated charcoal at pH3 was found to significantly increase drug protein binding in uremic sera. This effect was studied with six different drugs in sera from groups of 6 normal subjects and 8 patients on chronic hemodialysis. The percentage of sulfamethoxazole, dicloxacillin, diphenylhydantoin, salicylate, and digitoxin bound to protein in normal sera (65.9, 97.1, 93.1, 96.7, and 92.7, respectively) was unchanged by charcoal treatment. In contrast, charcoal treatment significantly (p less than 0.01) increased the percentage of drug bound to protein in uremic sera from 41.7 to 59.0 for sulfamethoxazole, 90.7 to 96.3 for dicloxacillin, 84.3 to 90.8 for diphenyhydantoin, 86.4 to 93.8 for salicylate, and 89.5 to 90.9 for digitoxin. Charcoal treatment significantly (p less than 0.05) reduced penicillin protein binding in normal sera and failed to correct the binding defect for penicillin in uremic sera. The effect of charcoal can be explained by removal of an inhibitor which accumulates in uremia and (1) occupies the binding site of certain drugs, (2) changes the configuration of the albumin molecule, or (3) both. Free fatty acid (FFA) concentrations in uremic patients were similar to those in normal subjects and were not the cause of the binding defect.