Hemolytic-uremic syndrome without evidence of microangiopathic hemolytic anemia on peripheral blood smear.

We report the case of an 18-year old man with hemolytic-uremic syndrome (HUS) having a classic clinical presentation and diagnostic renal pathology without evidence of microangiopathic hemolytic anemia (MAHA) by peripheral blood smear. Indirect evidence of hemolysis was suggested by mild anemia, elevation of serum lactate dehydrogenase, and examination of the patient's bone marrow. We postulate that in this case the inability to detect schistocytes in the peripheral smear reflected a low degree of hemolysis. Review of the literature revealed that evidence of fragmented erythrocytes by peripheral smear is not always present in HUS, yet this observation has received little attention. Thus, the diagnosis of HUS need not include overt evidence of MAHA as is traditionally taught.

Does hemodilution exist? Effects of saline infusion on hematologic parameters in euvolemic subjects.

The effects of intravenous fluids on hematocrit are debated. We sought to determine whether maintenance or bolus fluid therapy causes a significant change in the hematocrit and other hematologic parameters included in the complete blood count. Nine subjects completed a randomized three-period crossover designed trial in which they were given no fluid, maintenance fluid, or a bolus of fluid followed by maintenance fluid. We measured complete blood counts at baseline, 1 hour, 4 hours, and 8 hours. In the bolus fluid trial, the hemoglobin and hematocrit values (mean +/- SEM) decreased by a maximum of 1.5 +/- 0.1 g/dL and 4.1 +/- 0.3% at 1 hour. There was no difference in hemoglobin or hematocrit during the no fluid or maintenance fluid treatments. No significant changes occurred in white blood cell or platelet counts. We demonstrated that maintenance fluid infusions do not significantly after the complete blood count. Saline bolus is associated with a significant decrease in hemoglobin and hematocrit, but these parameters trend toward baseline over time.

Gitelman's variant of Bartter's syndrome, inherited hypokalaemic alkalosis, is caused by mutations in the thiazide-sensitive Na-Cl cotransporter.

Maintenance of fluid and electrolyte homeostasis is critical for normal neuromuscular function. Bartter's syndrome is an autosomal recessive disease characterized by diverse abnormalities in electrolyte homeostasis including hypokalaemic metabolic alkalosis; Gitelman's syndrome represents the predominant subset of Bartter's patients having hypomagnesemia and hypocalciuria. We now demonstrate complete linkage of Gitelman's syndrome to the locus encoding the renal thiazide-sensitive Na-Cl cotransporter, and identify a wide variety of non-conservative mutations, consistent with loss of function alleles, in affected subjects. These findings demonstrate the molecular basis of Gitelman's syndrome. We speculate that these mutant alleles lead to reduced sodium chloride reabsorption in the more common heterozygotes, potentially protecting against development of hypertension.

Effect of citrate on serum aluminum concentrations in hemodialysis patients: a prospective study.

Twenty hemodialysis patients were prospectively evaluated to determine if concomitant citrate and aluminum administration enhances the absorption of aluminum, thereby increasing the possibility of toxicity. The four-phase study consisted of phase I, a washout phase; phase II, an aluminum treatment phase; phase III, a treatment phase combining aluminum and soluble calcium citrate; and phase IV, a treatment phase with the patient's original prestudy phosphate binder. Results disclosed a progressive rise in serum aluminum levels (microgram/L) from 47 +/- 8 (phase I) to 62 +/- 12 (phase II) to 74 +/- 13 (phase III) and a drop to 58 +/- 12 (phase IV). The difference in levels between phases I and III was significant. Additionally, and despite the fact that serum calcium concentrations did not change, serum phosphate and immunoreactive parathyroid hormone concentrations were significantly lower when aluminum and citrate were used together. This suggests that citrate enhances the absorption of aluminum and therefore increases the possibility of toxicity in the patient with end-stage renal disease.

Cardiovascular effects of pseudoephedrine in medically controlled hypertensive patients.

BACKGROUND: Oral sympathomimetics are effective in the treatment of nasal congestion through stimulation of alpha-adrenergic receptors in the blood vessels of the nasal mucosa. This vasoconstrictor activity has resulted in the general recommendation that such pressor amines not be used in patients with hypertension. No prospective studies have examined the safety of sustained-release pseudoephedrine in hypertensive patients. METHODS: Volunteers (N = 28) with controlled hypertension participated in a randomized, double-blind, placebo-controlled, crossover study that examined the cardiovascular effects of 120 mg of sustained-release pseudoephedrine taken on a twice daily basis. Physician-investigators measured blood pressure and heart rate using mercurial sphygmomanometers during acute and steady-state phases. Compliance was verified with pill counts and serum drug levels. Symptom questionnaires were completed by the volunteers. RESULTS: While a strong statistical correlation was found over time, with minimal increases in mean arterial pressure and heart rate, pseudoephedrine administration did not result in statistically significant changes in any cardiovascular parameter. Mild disturbances in sleeping pattern and urinary retention in some male subjects were the only significant symptoms detected. CONCLUSIONS: We conclude that while sustained-release pseudoephedrine appears safe for the majority of medically controlled hypertensive patients without statistically significant effects on blood pressure or heart rate our studies did show an upward trend in these parameters which, in a larger population of hypertensive patients, may prove to be clinically significant.

Free and total 1,25-dihydroxyvitamin D levels in subjects with renal disease.

Patients with nephrotic syndrome and varying degrees of renal failure, including those on chronic hemo- and peritoneal dialysis, may have low serum concentrations of total 1,25-dihydroxyvitamin D [1,25(OH)2D]. However, it is unknown whether the true activity of 1,25(OH)2D is better reflected by the free 1,25(OH)2D fraction. We measured total 1,25(OH)2D, free 1,25(OH)2D, and vitamin-D-binding protein (DBP) in normal subjects (group A), subjects with moderate renal failure (group B), subjects on hemodialysis (group C), subjects on peritoneal dialysis (group D), and subjects with nephrotic syndrome (group E). The serum concentrations of total and free 1,25(OH)2D decreased with worsening renal function in groups A through C, with a high degree of correlation (r = 0.974, P less than 0.0001). Levels of DBP and the percent free 1,25(OH)2D remained constant in these groups. Patients on peritoneal dialysis and nephrotic patients had lower levels of DBP (203 +/- 14 micrograms/ml and 371 +/- 46 micrograms/ml, respectively) than normal subjects (436 +/- 33 micrograms/ml) and had significantly higher percent free 1,25(OH)2D (0.98 +/- 0.13% and 1.27 +/- 0.14%, respectively) compared to 0.63 +/- 0.03% (P less than 0.05). Thus, the loss of DBP in these patients correlated with a rise in the percent free 1,25(OH)2D. We conclude that levels of total 1,25(OH)2D are an accurate representation of 1,25(OH)2D status in normal subjects, subjects with renal insufficiency without nephrotic syndrome, and hemodialysis patients. In peritoneal dialysis and nephrotic patients, who lose DBP, measurements of free 1,25(OH)2D may be necessary in order to accurately assess 1,25(OH)2D status.

Does magnesium play a role in the hypokalemia of Bartter's syndrome?

A patient with Bartter's syndrome manifested hypomagnesemia in addition to hypokalemia. Under conditions of maximal free water production, he had a fractional distal solute reabsorption of 0.65, a value consistent with a renal defect in sodium chloride reabsorption in the thick ascending limb of the loop of Henle. This is also the site of 65% to 70% of urinary magnesium reabsorption. With magnesium supplementation and amiloride, the urinary potassium decreased and the serum potassium increased. Atrial natriuretic peptide concentrations in the plasma were low. Evaluation of family members showed five of nine offspring had hypokalemia with no disorder in the parents, an apparent autosomal recessive mode of inheritance. This is a US government work. There are no restrictions on its use.

Emergencies in continuous dialysis patients: diagnosis and management.

The number of patients undergoing long-term hemodialysis and peritoneal dialysis is growing in the United States. To provide adequate emergent care to these patients emergency physicians must understand the alterations in normal physiologies present in these patients and how this may affect care. Cardiovascular disease and infection (especially Staphylococcus aureus sepsis) are the leading causes of death among dialysis patients. These patients are also subject to a significantly higher incidence of life-threatening electrolyte disturbances, particularly hyperkalemia and hypercalcemia, than the general population. Suicide, cardiac tamponade, intracranial hemorrhage, bleeding disorders, and bowel infarction are also much more frequent. The inability of dialysis patients to excrete drugs, metabolites, toxins, and fluids significantly alters their responses to common emergencies and should directly influence their care. Failure to recognize these differences in physiology may result in the use of standard forms of emergency therapy that may compound, rather than treat, the underlying disorder. Although most dialysis patients who come into an emergency department have conditions that can, and should, be managed by their nephrologist, the presence of a life threatening emergency requires prompt, appropriate therapy by the emergency physician.

Back to basics: the urinalysis: a selected national survey and review.

An accurately performed urinalysis is vital to the screening and assessment of renal disease. We sent questionnaires to nephrology training programs throughout the United States and compared techniques described in the responses to standard urinalysis methodology gleaned from literature review. There were notable deviations in performance and interpretation between the nephrologists and the standard urinalysis. It appears that additional emphasis should be place don this basic and important laboratory test. Further study is needed to determine if more accurate performance will influence patient diagnosis and outcome.

Calcium citrate, a nonaluminum-containing phosphate-binding agent for treatment of CRF.

Calcium citrate was evaluated as a dietary phosphate binder in 81 patients with end-stage renal disease. These patients were grouped as follows: Group 1, 43 patients who were treated with calcium citrate; and Group 2 (the control group), 38 patients who were treated with aluminum-containing compounds. Blood chemistries were measured monthly and medications adjusted to maintain the following levels: serum calcium, greater than 9 mg/dl; serum phosphorus, less than 5.5 mg/dl; and total CO2 content, greater than 22 mmol/liter. At the end of the treatment period, the following serum values were obtained in Groups 1 and 2, respectively: calcium, 9.6 +/- 1.2 mg/dl (mean +/- SD) versus 8.9 +/- 0.8 mg/dl (P less than 0.001); phosphorus 5.5 +/- 1.9 mg/dl versus 7.0 +/- 2.3 mg/dl (P less than 0.005); and calcium-phosphate product, 52 +/- 18 versus 61 +/- 21 (P less than 0.05). Differences in alkaline phosphatase, total CO2 content, and C-terminal parathyroid hormone (C-PTH) values were not statistically significant between the two groups. Fifteen patients in Group 1 were then switched to aluminum-containing compounds and chemistries were compared one month later. During calcium citrate therapy, serum calcium was significantly higher, while C-PTH and serum alkaline phosphatase were significantly reduced. No difference was noted in serum phosphorous and total CO2 content. A questionnaire completed by 17 patients in Group 1 documented excellent patient tolerance to calcium citrate. Hypercalcemia (greater than 10.5 mg/dl) was the only significant complication, but only one patient became symptomatic. We conclude that, as a phosphate binder, calcium citrate is at least as effective as aluminum-containing compounds.

Sexual dysfunction in the male dialysis patient: pathogenesis, evaluation, and therapy.

Impotence is a common problem in male dialysis patients. Although dialysis patients may appear to have more reasons to be depressed than nondialysis patients, depression has not been found to be correlated with erectile dysfunction in this group. Primary testicular failure is common in male dialysis patients as is hyperprolactinemia. These disorders may be the cause of impotence in some of these patients. An algorithm for the evaluation and treatment of impotence in the male dialysis patient is presented. Successful renal transplantation is associated with improvement in the testicular failure, in the hyperprolactinemia, and in the erectile dysfunction of the male patient with end-stage renal disease.

Mineralocorticoid-induced kaliuresis in type-II pseudohypoaldosteronism.

Type II pseudohypoaldosteronism is an uncommonly reported disorder. The authors recently evaluated a patient who in many respects appeared to have this syndrome. He had hyperkalemia, a normal glomerular filtration rate, "normal" serum and urinary aldosterone levels, and low plasma renin activity. In addition, he had a hyperchloremic metabolic acidosis and hypertension. Fractional excretion of potassium was reduced in response to sodium chloride loading. However, renal potassium excretion in response to administration of sodium sulfate was normal. Thiazide diuretic restored the serum potassium, the low bicarbonate, and blood pressure to normal. He developed marked natriuresis and kaliuresis in response to high-dose exogenous mineralocorticoid. The magnitude of the kaliuretic response achieved to exogenous mineralocorticoid has been reported only once previously.

Review: Renal osteodystrophy--pathogenesis and treatment.

Histologic bone changes of osteitis fibrosa and osteomalacia are commonly present in patients with end-stage renal disease. Although many patients are not symptomatic from these bone changes, some patients are severely disabled. Altered metabolism of vitamin D, calcium, phosphorus, and parathyroid hormone occurs in renal failure and contributes to the development of uremic bone disease. This article reviews the current theories of pathogenesis and treatment of renal osteodystrophy. In addition, the clinical presentation, pathogenesis, and treatment of the various aluminum-associated osteomalacic syndromes in uremia are discussed.

Role of volume depletion in the glycerol model of acute renal failure.

Previous studies have demonstrated significant volume depletion early in the course of glycerol-induced acute renal failure. In addition, it has been shown that acute volume expansion within 6 h of glycerol administration reverses the fall in inulin clearance but volume expansion 12-24 h after glycerol fails to restore that parameter to normal. The current studies were performed to determine whether chronic volume expansion would prevent the fall in inulin clearance normally observed 18-20 h after the insult. Inulin clearance was therefore compared 18-20 h after glycerol in hydropenic rats and in rats undergoing chronic volume expansion by the constant infusion of Ringer solution at a rate of 5 ml/h initiated at the time of the glycerol injection. Inulin clearance was well maintained in the latter group, averaging 1.77 compared with 0.22 ml/min in the hydropenic group. Renal histology revealed no difference in the degree of tubular necrosis between groups but did show a marked decrease in cast formation in the animals undergoing chronic volume expansion. To determine the possible significance of these casts, micropuncture studies were carried out to measure proximal tubular pressures. Under hydropenic conditions these pressures were not different control animals and rats receiving glycerol when studied 18-20 h after glycerol. Following acute volume expansion, however, glycerol-treated rats demonstrated significantly higher pressures than control rats. On the other hand, proximal tubular pressures were comparable in glycerol-treated and control animals receiving the chronic volume expansion.(ABSTRACT TRUNCATED AT 250 WORDS)

Renal osteodystrophy--pathogenesis and treatment.

Histologic bone changes of osteitis fibrosa and osteomalacia are commonly present in patients with end-stage renal disease. Although many patients are not symptomatic from these bone changes, some patients are severely disabled. Altered metabolism of vitamin D, calcium, phosphorus, and parathyroid hormone occurs in renal failure and contributes to the development of uremic bone disease. This article reviews the current theories of pathogenesis and treatment of renal osteodystrophy. In addition, the clinical presentation, pathogenesis, and treatment of the various aluminum-associated osteomalacic syndromes in uremia are discussed.

Acute interstitial nephritis associated with mezlocillin, nafcillin, and gentamicin treatment for Pseudomonas infection.

Two patients developed acute interstitial nephritis (AIN) following treatment with mezlocillin sodium. Diagnosis was made by renal biopsy. Gallium 67 citrate scanning was abnormal in both. All patients were receiving multiple-drug therapy, but AIN has either not been described with the other drugs, or the temporal relationship between the AIN and termination of other drug therapy makes a causative relationship unlikely. All were infected with Pseudomonas aeruginosa. A role for the infecting organism or drug synergism in contributing to the renal disease cannot be excluded.