Does pyuria indicate infection in asymptomatic dialysis patients?

It has been suggested that the finding of leukocyturia > 10 WBC/HPF in asymptomatic dialysis patients predicts a positive urine culture and hence indicates urinary tract infection. Seventeen asymptomatic ESRD patients contributed clean catch specimens. Nine patients had ten or more WBC/HPF. One of these grew a possible pathogen in pure culture (23% of specimens excluding those growing multiple organisms). Thus, leukocyturia is not a good marker for positive urine culture and moreover is not demonstrated to indicate infection even when positive cultures follow.

Light chain nephropathy in a 19-month-old boy with AIDS.

A 19-month-old boy with AIDS developed clinically unexplainable proteinuria. Biopsied renal tissue was examined by light microscopy, transmission electron microscopy, and immunofluorescence. Findings included an increase of mesangial matrix with occasional nodular sclerosis, mesangial hypercellularity, and glomerular deposits of kappa and lambda light chains. There were deposits of kappa, but not lambda, light chains in the arteriolar walls, and around the tubular and interstitial capillary basement membranes. Quantitative urinary immunoelectrophoresis revealed an extremely high urinary concentration of kappa light chain. These changes are diagnostic of light chain nephropathy. The rarity of light chain nephropathy in childhood and its occurrence in a patient with AIDS make this case unusual.

A bold mold? Paecilomyces variotii peritonitis during continuous ambulatory peritoneal dialysis.

A patient on peritoneal dialysis developed peritonitis due to Paecilomyces variotii. It appears that this relatively rare organism may be starting to assert itself as a more important human pathogen. A plea is made for speciation.

Normal T lymphocyte function in patients with end-stage renal disease hemodialyzed with 'high-flux' polysulfone membranes.

T lymphocyte function was analyzed in patients hemodialyzed with 'high-flux' polysulfone membranes, which have been reported to improve the patients' overall clinical condition and well-being. For comparison purposes, patients treated by the use of 'low-flux' cuprophane membranes were also studied. Peripheral blood white cell counts, numbers of lymphocytes as well as the numbers of T cells and their CD4 and CD8 subsets were within normal range in both patient groups. The absolute number of B cells was slightly decreased in cuprophane-membrane- but not polysulfone-membrane-treated patients. The proliferative response of T lymphocytes after stimulation with optimal concentration of phytohemagglutinin (PHA) was normal in patients treated with 'high-flux' membrane dialysis but significantly reduced in those treated with cuprophane membranes. The generation of interleukin-2 (IL-2) receptor on T lymphocytes after PHA stimulation was normal in the polysulfone-membrane-treated group and slightly impaired in the cuprophane-membrane-dialyzed patients. Production of both IL-2 and interleukin-1, as well as the natural killer cell activity, in patients treated by 'high-flux' membrane dialysis were also comparable to controls. The levels of serum beta 2-microglobulin were significantly elevated in patients-maintained on 'high-flux' dialysis membranes but did not reach the levels seen in patients dialyzed by cuprophane membranes. The beta 2-microglobulin at levels seen in patients on cuprophane dialysis had no effects on activation and proliferation of control lymphocytes in vitro. These results suggest that impaired functional responses of T lymphocytes seen in end-stage disease patients on prolonged hemodialysis with cuprophane membranes are not seen in similar patients hemodialyzed with polysulfone membranes.

Digoxin-like immunoreactive substance in chronic hemodialysis patients: effect on digitoxin radioimmunoassay.

Digoxin-like immunoreactive substance(s) (DLIS) in the sera of patients with renal insufficiency may confound attempts to monitor serum digoxin levels. We investigated whether DLIS would affect the radioimmunoassay (RIA) for digitoxin. DLIS was detected by RIA in 9 of 38 chronic hemodialysis patients and in none of 25 healthy controls. Digitoxin levels were not elevated in either the control or dialysis group, and false-positive results for digitoxin by RIA were not obtained in any patient with DLIS. It is concluded that DLIS does not interfere with the digitoxin RIA, nor are digitoxin levels spuriously elevated in chronic hemodialysis patients. Digitoxin may be a preferable preparation for digitalis-dependent dialysis patients with DLIS.

B-cell activation and immunoregulation in end-stage renal disease patients receiving hemodialysis.

B-lymphocyte functions were studied in peripheral blood mononuclear cells of end-stage renal disease patients undergoing intermittent hemodialysis for longer than two years. T-cell-dependent B lymphocyte proliferation after pokeweed mitogen stimulation was low in half of the hemodialyzed patients. T cell-independent B cell response to Staphylococcus aureus, Cowan I, was also significantly reduced. Spontaneous production of immunoglobulin in cultures of peripheral blood mononuclear cells of uremic patients was comparable with that of healthy controls, but pokeweed mitogen-stimulated antibody secretion was significantly reduced with cells from patients undergoing hemodialysis. Helper T-cell functions in B-cell activation were also qualitatively deficient in uremic patients. It is concluded that B-cell activation and immunoregulation is defective in patients undergoing long-term hemodialysis.

The effect of dialysate calcium levels on blood pressure during hemodialysis.

A controlled double-blind prospective study was undertaken of the effect of dialysate calcium levels on BP during hemodialysis. Twenty patients and 240 dialyses were studied using a protocol in which patients underwent alternate hemodialyses with dialysate calcium of 2.5 and 3.5 mEq/L. Dialysate composition was otherwise the same. Mean BPs during dialysis were significantly lower at 1.5, 2.5, and 3.5 hours of dialysis when the lower dialysate calcium was used (P = .007 to .02). However, the difference in BP between the high and low dialysate calcium treatments was clinically minor, with a maximum mean difference (at 1.5 hours) of 4.6 mm Hg. Subgroups of patients with frequent hypotension and low or normal serum calcium did not appear more sensitive to the hypotensive effect of low calcium dialysate. Dialysate calcium levels of 2.5 and 3.5 mEq/L thus differ in their effect on intradialytic BP in a statistically significant, but clinically minor, way. Low calcium dialysate thus may prove useful in the management of patients in whom large amounts of enteric calcium absorption are indicated or unavoidable.

The missing gap. A pitfall in the diagnosis of alcohol intoxication by osmometry.

An osmolal gap (a disparity between measured and calculated serum osmolality) may accompany alcohol intoxication. We encountered a patient with methanol toxicity in whom no such gap was present, despite a markedly elevated serum methanol level. Further investigation revealed that serum osmolality had been measured with a vapor pressure osmometer; this technique may not detect volatile solutes such as alcohols. In vitro testing confirmed the insensitivity of vapor pressure osmometry to toxic ranges of both methanol and ethanol. When alcohol toxicity is suspected, an osmolal gap should be sought only if freezing point osmometry is available.

T cells in patients undergoing chronic hemodialysis: mitogenic response, suppressor activity, and interleukin-2 production and receptor generation.

The functional response of peripheral blood T lymphocytes was studied in patients with end-stage renal disease treated by chronic hemodialysis for over 1 year. Proliferation after phytohemagglutinin stimulation of patients' peripheral blood mononuclear cells and of T lymphocyte fractions isolated by either sheep erythrocyte rosetting or by use of a nylon wool column was significantly reduced as compared with that of corresponding fractions from healthy control subjects (P less than 0.001). The induction of suppressor cell activity by concanavalin A in rosetted T cell fractions was higher with cells of hemodialyzed patients than with control cells (P less than 0.025). The expression of class II MHC antigen (HLA-DR) by the T8 lymphocyte subset after concanavalin A induction, as determined by staining with monoclonal antibodies and two-color fluorescence analysis by flow cytometry, was also higher in hemodialyzed subjects (P less than 0.025). Since contamination by non-T cells in such cell fractions and increases in proliferation after indomethacin treatment of peripheral blood mononuclear cells were similar in hemodialyzed and control subjects, it is unlikely that the depressed T lymphocyte responses and the increased suppressor cell activity can be attributed to increased peripheral blood monocyte counts observed in patients undergoing hemodialysis. Studies of the biological events associated with the activation of lymphocytes of hemodialyzed patients revealed a reduction in expression of interleukin 2 receptor in the plasma membrane of phytohemagglutinin-stimulated lymphocytes as determined by staining with monoclonal antibody (P less than 0.01). In addition, a very low secretion of interleukin 2 by stimulated peripheral blood mononuclear cell populations was observed in about one-half of patients receiving hemodialysis.

Variability in potassium removal by hemodialysis.

The extent to which plasma potassium determines potassium removal in hemodialysis was examined in 8 end-stage renal disease patients during 51 treatments. Dialyzers, treatment time, blood and dialysate flow were held constant. Dialysate composition was also uniform except that 24 treatments utilized glucose-free dialysate and the remaining 27 a 200 mg/dl glucose bath. At either level of dialysate glucose, approximately 40% of the potassium removal during dialysis could not be accounted for by plasma-dialysate potassium gradient, body weight or serum carbon dioxide content, although glucose-free dialysate tended to increase potassium removal by a mean of 28%. The large, unexplained variability in potassium removal suggests that therapeutic manipulation of potassium flux across cell membranes may improve the management of potassium balance in hemodialyzed patients.

Thrombocytopenia associated with intravenous desferrioxamine.

Desferrioxamine (DFO) was administered intravenously to a 63-year-old chronic hemodialysis patient with osteomalacia believed secondary to aluminum intoxication. Thrombocytopenia was noted after five doses of DFO. Platelet counts normalized after DFO was withheld. Thrombocytopenia recurred upon two rechallenges with this drug. It is suggested that platelet counts be monitored in hemodialysis patients receiving intravenous DFO.

Amelioration of hemodialysis-associated hypotension by the use of cool dialysate.

The effect of a reduction in dialysate temperature on BP during hemodialysis was studied in seven patients with end-stage renal disease suffering frequently from intradialytic hypotension. Each patient received six dialyses using 34.4 degrees C dialysate. These treatments were preceded (six dialyses) and also followed (six dialyses) by control periods using a 36.7 degrees C bath. Symptomatic hypotension was defined as systolic BP below 100 mm Hg associated with typical symptoms of hypotension requiring treatment with intravenous (IV) fluid. Cool dialysate reduced the frequency of symptomatic hypotension from 0.58 to 0.05 episodes per dialysis (P = less than 0.016). In addition, the rate of fall of mean BP during treatment was substantially slowed with the reduction in dialysate temperature (P = 0.002). Cool dialysate (34.4 degrees C) substantially ameliorates hemodialysis-associated hypotension.

Effect of variations in dialysate temperature on blood pressure during hemodialysis.

The effect on BP of alteration in dialysate temperature was studied in 150 hemodialysis treatments in 17 patients using a randomized, double-blind protocol. Each patient was treated using dialysate at 35.6 degrees C, 36.7 degrees C, and 37.8 degrees C. Mean BP during 35.6 degrees C dialysis was significantly higher than during 36.7 degrees C or 37.8 degrees C treatments. Symptomatic hypotensive episodes were more frequent at a dialysate temperature of 37.8 degrees C than during use of cooler dialysates. Modest changes in dialysate temperature thus appear to affect BP during hemodialysis. Dialysate cooler than that routinely employed has a beneficial effect while warmer dialysate has a detrimental one on intradialytic BP. The use of dialysate at least 1 degree C cooler than "isothermic" levels may be appropriate.

Suppressor cells in end-stage renal disease. Functional assays and monoclonal antibody analysis.

Suppressor cell activity after concanavalin A induction was studied in peripheral blood mononuclear cells of patients undergoing long-term hemodialysis. Suppression both of the mixed lymphocyte reaction and of allogeneic cells stimulated with phytohemagglutinin was significantly higher with peripheral blood mononuclear cells from patients undergoing hemodialysis than with cells from control subjects. Expression of the Ia antigen on T lymphocytes (associated with immunologic activation) was studied by staining with monoclonal antibodies and two-color fluorescence analysis in a computer-linked cytofluorograph. In unstimulated cells, there was no significant difference between the patients and control subjects. After concanavalin A induction, the percentage of T4, and particularly of T8, cells expressing the Ia antigen was significantly higher in the group undergoing hemodialysis. The functional suppression seen after concanavalin A induction in the mixed lymphocyte reaction was significantly reduced by treatment with OKT8 monoclonal antibody and complement; in phytohemagglutinin cultures, both OKT8 and OKIa*1 antibodies were effective. The reduced in vitro response of uremic lymphocytes may thus be a consequence of increased suppressor activity associated with the T8-positive, Ia-positive subset of T cells.

T cell subsets and cellular immunity in end-stage renal disease.

The T lymphocyte population was studied by immunofluorescent staining with monoclonal antibodies and laser flow cytometry in the blood of 50 patients with end-stage renal disease undergoing long-term maintenance intermittent hemodialysis. The absolute number of T cells was lower in patients receiving dialysis for more than one year (p less than 0.001), as was the absolute count of helper T cells (p less than 0.005). In patients under 30 years of age, the absolute number of helper T cells was markedly reduced, whereas the number of suppressor/cytotoxic T lymphocytes was not changed. In patients between the ages of 30 and 60 years, both helper and suppressor cells were significantly reduced. In patients over 60 years of age, only the number of helper T cells was reduced. The in vitro response of patients' lymphocytes was reduced both in the mixed lymphocyte reaction (p less than 0.01) and after phytohemagglutinin stimulation (p less than 0.001). Natural killer cytotoxicity of patients' peripheral blood mononuclear cells, however, was unaffected.

Urinary sodium and chloride during renal salt retention.

One hundred ten episodes of renal salt retention (urinary sodium and/or chloride less than 10 mEq/L) were studied retrospectively to determine the significance of discordance of urinary sodium from chloride. In 16 episodes the urinary sodium exceeded chloride by at least 15 mEq/L. This disparity was associated with the necessity for urinary excretion of substantial quantities of poorly reabsorbed anions (penicillin, ketones, or diatrizoate), a rapidly falling serum bicarbonate level (due to resolving metabolic or developing respiratory alkalosis), or substantial renal insufficiency (serum creatinine greater than 3 mg/dL). In 14 of 110 episodes, urinary chloride exceeded urinary sodium by at least 15 mEq/L. These patients were more often oliguric and had a higher mean serum chloride than patients without this dissociation. In patients with oliguria, hyponatremia, or metabolic alkalosis, measurement of urinary sodium or chloride alone will, in a substantial number of cases, fail to detect renal salt retention. When evidence is sought for renal salt retention, both urinary sodium and chloride should be determined.