Glomerulopathies with fibrillary deposits.

Renal diseases involving glomerular deposits of fibrillary material are an important diagnostic challenge for the ultrastructural pathologist. Two primary disorders of this type, termed "fibrillary glomerulonephritis" (characterized by fibrils measuring approximately 20 nm in diameter) and "immunotactoid glomerulopathy" (characterized by larger, microtubular deposits), have been described. The possible relatedness of these two disorders and their potential association with other systemic illnesses are subjects of current debate. Other multisystemic diseases, including amyloidosis and various forms of cryoglobulinemia, can also present with fibrillary or microtubular deposits in the kidney. Five cases are presented in which fibrillar or microtubular structures were identified in renal biopsies by ultrastructural examination. The distinction between fibrillary glomerulonephritis, immunotactoid glomerulopathy, and other processes that have similar ultrastructural features are discussed.

Biochemical effects of oral sodium phosphate.

Our objective was to monitor serum and urine biochemical changes after oral sodium phosphate cleansing in a prospectively designed study. The study subjects were seven healthy, asymptomatic adults. Sodium phosphate 45 ml diluted in 45 ml water was given orally at baseline and 12 hr later. Calcium, ionized calcium, phosphorus, sodium, potassium, creatinine, and PTH were analyzed at 2, 4, 6, 9, 12, 14, 16, 18, 21 and 24 hr after the first challenge. Urinary calcium, phosphorus, sodium, potassium, and cyclic AMP were analyzed at baseline and every 2 hr after oral sodium phosphate. Blood pressure, pulse, and respiratory rate were recorded every 2 hr and symptom questionnaires using visual analog scales were completed. A marked rise in phosphorus (peak range 3.6-12.4 mg/dl, P < 0.001) and falls in calcium (P < 0.001) and ionized calcium (P < 0.001) were seen. Rises seen in PTH and urinary cAMP confirmed the physiologic significance of the biochemical effect. There were no significant changes in other serum and urine laboratory or clinical assessments. Reported significant symptoms included bloating, cramps, abdominal pain, and nausea. Significant hypocalcemia and hyperphosphatemia after oral sodium phosphate raises concern about its use in normal individuals. Oral sodium phosphate should not be administered in patients with cardiopulmonary, renal, or hepatic disease.

Frequency of complications with prolonged femoral vein catheterization for hemodialysis access.

Analysis of 120 cases of femoral vein catheterization for > or = 2 days for hemodialysis in 89 hospitalized patients was performed to determine the frequency of catheter-related complications including infection and venous thrombosis. The rate of clinically significant complications was < 3.5% and compared favorably with published complication rates of central vein catheters. We conclude that prolonged femoral vein catheterization for hemodialysis is associated with an acceptably low rate of complications when appropriate techniques for placement and catheter care are followed and should be considered a reasonable option for vascular access in hospitalized patients.

Sweet taste (dysgeusia). The first symptom of hyponatremia in small cell carcinoma of the lung.

Three patients with small cell carcinoma of the lung presented with a persistent unpleasant sweet taste as their initial and only symptom. On further evaluation, they were found to have hyponatremia secondary to the syndrome of inappropriate secretion of antidiuretic hormone. In each case, resolution of the sweet taste paralleled an increase in serum sodium concentration after water restriction alone. Linkage of the sweet taste with a low serum sodium concentration strongly implicates hyponatremia--rather than tumor, antidiuretic factor, medications, or chemotherapy--as the central mechanism responsible for this previously unreported (to our knowledge) sentinel symptom of small cell carcinoma of the lung.

Hypertonic saline: patterns of and guidelines for use.

Guidelines for appropriate use of hypertonic (3%) saline (HS) for the treatment of hyponatremia are ill-defined. We reviewed each infusion of HS in a 400-bed university hospital over a 1-year period. Of the 14 infusions, the hyponatremia (average serum sodium [Na+] 19.9 +/- 6.7 mEq/L) was chronic in 11 cases and acute in only 3. In only 2 patients were there symptoms possibly attributable to hyponatremia. On the average, more than 5 hours elapsed from the last measured serum Na+ level to the initiation of HS infusion, and the next measured serum Na+ value came more than 6 hours later. HS should be reserved for symptomatically hyponatremic patients, most of whom become acutely hyponatremic. A target level for the serum Na+ should be determined and a time-course for correction set. The infusion should be started promptly and monitored frequently for the effect on the serum Na+ level and patient symptoms.

Clearance of 131I by hemodialysis.

There are no available data documenting the dialysis clearance of iodide in humans. This work quantitates the hemodialysis clearance of iodide (as 131I) over time and examines certain factors which influence that clearance. In a single-patient study, three dialysis periods were studied over the 24 to 96 hours following administration of 129 mCi 131I given as Na131I. Hemodialysis clearance of 131I was calculated both from the arterio-venous difference of 131I across the artificial kidney and the appearance of 131I in the expended dialysate. Calculations were based on 131I activity in whole blood, whole plasma, and the supernate of plasma treated with 10% trichloroacetic acid (TCA). The hemodialysis clearance of 131I was highest when calculated from the activity of the plasma supernate, 171.3 +/- 6.0 ml/min for the period 24-29 h. post dosing, and fell in a linear fashion with time. The clearance calculated from whole blood activity was always intermediate to that from whole plasma (lowest) or the plasma supernate (highest). The percentage of plasma 131I activity precipitated by TCA rose over the study period and displayed a strong negative correlation to the hemodialysis clearance of 131I. The hemodialysis clearance of iodide, as 131I, is on the order expected for a free ion and is 4-5 times higher than the endogenous renal clearance of the ion. However, the calculated clearance varies with respect to total time of dialysis and the fraction of blood in which the 131I activity is measured.(ABSTRACT TRUNCATED AT 250 WORDS)

Remnant kidney oxygen consumption: hypermetabolism or hyperbole?

On the basis of observations in surgically created remnant kidneys of rat and dog, a novel hypothesis for progressive injury in the setting of reduced renal mass has been put forth. Both rat and dog remnant kidneys exhibit significant hypertrophy that is accompanied by an increased rate of oxygen consumption (QO2) per remaining nephron but not per gram of tissue. This putative "hypermetabolism" is seen in the face of progressive scarring of the tubulointerstitial compartment of the remnant kidney, and interventions that reduce QO2 in these models have been associated with reduced tissue injury in previous studies. The proposed pathway by which an increase in QO2 leads to cellular damage is via the production of oxygen-reactive species or free radicals. In this article, the available data upon which this "hypermetabolism" hypothesis is based are reviewed and the constructs within which these data have been analyzed are examined. From these considerations, a set of questions not yet answered that may serve to direct more fruitful query into this intriguing problem

Case report: a novel form of free protein S deficiency in an HIV-positive patient on hemodialysis.

Investigation of repetitive thrombotic episodes in an HIV-positive patient on maintenance hemodialysis revealed extraordinarily high levels of total (free plus protein bound) protein S antigen but severe reductions in free (interactive) protein S antigen. Patients with the nephrotic syndrome or chronic renal failure have shown elevations of total protein S antigen, associated with increased levels of the specific C4b-binding protein, yet have had normal free protein S antigen levels. Based on the fall in total and free protein S levels during hemodialysis treatments, the presence of normal levels of C4b-binding protein, and the coexistence of a polyclonal gammopathy, the authors infer the presence of a unique protein that binds protein S in this patient and that is not apparent in normal plasma. The anomalous association of protein S with this binding protein resulted in levels of free protein S antigen in the range of those reported in hereditary deficiencies of the anticoagulant.

Measurement of intracellular pH in suspensions of renal tubules from potassium-depleted rats.

Intracellular pH was estimated from the fluorescence of 2',7'-bis(carboxyethyl)-5,6-carboxyfluorescein (BCECF) in isolated renal cortical tubules from control, potassium-depleted (KD) and NH4Cl-induced metabolic acidosis (MA) rats. While pHi was not different among control, short- and long-term KD, and NH4Cl MA rats, in vitro rates of ammonium production were increased in rats with metabolic acidosis and both short- and long-term potassium depletion. Mitochondrial matrix pH, and the pH gradient across the mitochondrial membrane were not different in tubules from KD rats compared to those from controls. These results are interpreted to indicate that a signal other than intracellular acidosis maintains the high rate of renal ammoniagenesis seen in KD.

Severe hyponatremia in spinal cord injury.

A male quadriplegic (C6--complete) with persistent chronic hyponatremia (serum sodium values ranging consistently from 117-132 mmol/L) developed acute hyponatremia with a serum sodium concentration of 98 mmol/L. This extreme hyponatremia related, in part, to a reversible defect in the excretion of a water load, while on a low (46 mmol/day) sodium diet. Subsequent ingestion of a normal sodium diet (150 mmol/day), with or without 0.1 mg of fludrocortisone (Florinef), reestablished his ability to excrete a water load normally. The etiology of this patient's hyponatremia is discussed as well as the unique concordance of factors which make hyponatremia a common occurrence among spinal-cord injured patients.

The pK'1 of the carbonic acid-bicarbonate buffer system in hemodialyzed patients.

Blood gas analysis is crucial for the proper evaluation of systemic acid-base disorders, but several reports have been critical of the current approach which relies on the Henderson-Hasselbalch equation and other possibly erroneous assumptions about the bicarbonate-carbonic acid buffer system of blood. This report studied renal failure patients receiving dialysis and nondialyzed medical patients with respect to variations of the pK'1 of carbonic acid dissociation and discrepancies between measured and calculated bicarbonate. Among dialyzed patients, the mean pK'1 differed significantly from 6.10, and a significant difference was found between calculated and measured total CO2 even though all assays were performed on the same arterial blood. Significant correlations were observed between pK'1 and calculated-measured total CO2 as well as serum phosphate converted to mEq/l in the dialyzed group. These data suggest that there is a need to reevaluate current acid-base analysis, especially as it is applied to very seriously ill individuals.

Proton compartmentation in rat renal cortical tubules.

To study the control of renal ammoniagenesis, a technique was developed to estimate simultaneously intracellular (pHi) and intramitochondrial (pHm) pH in suspensions of rat renal cortical tubules. pHi was estimated with the fluorescent probe 2',7'biscarboxyethyl-5(6)-carboxy-fluorescein (BCECF). The intracellular distribution of the weak acid 5,5-dimethyloxazolidine-2,4-dione (DMO) allowed calculation of pHm with the use of values of pHi obtained with BCECF and tubule mitochondrial content. At medium pH (pHe) 7.4, pHi was 7.08 +/- 0.02. Over the pHe range 7.0-7.7, pHi was linearly related to pHe, but the pH gradient across the cell membrane decreased as pHe was lowered. No difference in the relationship between pHe and pHi was obtained when tubules were incubated in the presence of a nonbicarbonate or bicarbonate-buffered medium. Changes in pHe with bicarbonate-buffered media resulted in identical pHi values, whether the changes were induced by altered bicarbonate or CO2 content. At pHe 7.4, pHm was 7.78 +/- 0.6 in bicarbonate-buffered medium but was higher (0.2-0.3 pH units) when tubules were bathed in nonbicarbonate-buffered medium. pHm was linearly related to pHi in either buffer. The pH gradient across the inner mitochondrial membrane was also positively correlated with pHe. The present studies indicate the suitability of the techniques for estimating pHi and pHm simultaneously in suspensions of rat renal cortical tubules. Parallel changes occur in both intracellular compartments when pHe is altered. pHm, which is approximately 0.7 pH units greater than pHi, decreases in acute acidosis. This decrease may be important in stimulating renal ammoniagenesis, possibly by activation of alpha-ketoglutarate dehydrogenase.

Renal gluconeogenesis.

Gluconeogenesis, the de novo formation of glucose from non-carbohydrate precursors, is confined to the proximal convoluted and proximal straight tubules of the mammalian kidney. Compared to liver, renal gluconeogenesis has different substrate requirements and responds to different regulatory stimuli. Stimuli in kidney include starvation, metabolic acidosis, glucocorticoid treatment, and, possibly, PTH and catecholamines. Regulation of gluconeogenic flux occurs at three or four key enzyme sites, particularly phosphoenolpyruvate carboxykinase (PEPCK) and fructose 1,6-bisphosphatase. Interest has focused on the relation among H+, Ca2+, and cyclic AMP in the hormonal regulation of gluconeogenesis. The importance of other putative regulators including fructose 2,6-bisphosphate remains to be determined.

PGE2, forskolin, and cholera toxin interactions in modulating NaCl transport in mouse mTALH.

Prostaglandin E2 (PGE2) inhibits the ADH-stimulated components of the lumen-positive transepithelial voltage (Ve) and of net chloride absorption (JnetCl) in the isolated microperfused mouse medullary thick ascending limb of Henle (mTALH), presumably by interfering with the ADH-dependent intracellular accumulation of cAMP. These experiments examined the interactions of PGE2 with two nonhormonal stimulators of adenylate cyclase--cholera toxin and forskolin--in an attempt to evaluate the means by which PGE2 inhibits ADH-stimulated transport in these mTALH segments. Forskolin (FSK) stimulated Ve in the mTALH with half-maximal stimulation at 1.4 X 10(-7) M FSK. PGE2 had no effect on FSK stimulation of Ve; 10(-6) M FSK reversed completely the PGE2 inhibition of ADH-stimulated Ve. A low concentration of cholera toxin, 5 X 10(-13) M, stimulated Ve and JnetCl in the mTALH; 10(-6) M PGE2 inhibited the stimulation by cholera toxin; and 10(-6) M FSK reversed the PGE2 inhibition of both Ve and JnetCl in cholera toxin-stimulated mTALH. A higher concentration of cholera toxin, 10(-10) M, stimulated Ve and JnetCl to values identical to those seen with maximal concentrations of ADH, but PGE2 did not inhibit the increments in either Ve or JnetCl produced by 10(-10) M cholera toxin. PGE2 appears to inhibit ADH stimulation of NaCl transport in mTALH by an action distal to hormone-receptor interactions yet proximal to the catalytic subunit of adenylate cyclase.

Interactions among prostaglandin E2, antidiuretic hormone, and cyclic adenosine monophosphate in modulating Cl- absorption in single mouse medullary thick ascending limbs of Henle.

This paper describes the inhibitory effect of prostaglandin E2 (PGE2) on antidiuretic hormone (ADH)-stimulated net Cl- absorption and spontaneous transepithelial voltage (Ve) in single medullary thick ascending limbs of Henle (TALH, thick ascending limb; mTALH, medullary segment; cTALH, cortical segment) obtained from mouse kidney. The experimental data indicate that PGE2 reduced the ADH-dependent values of net Cl- absorption (JnetCl, eq cm-2 s-1) and Ve (mV) in a dose-dependent manner; that increasing concentrations of peritubular ADH reversed the PGE2-mediated reductions in the ADH-dependent moiety of Ve in the mouse mTALH; that PGE2 had no effect on cyclic AMP-stimulated increments in Ve in the mouse mTALH; and that PGE2 had no effect on Ve in the cTALH, where Ve is unaffected either by ADH or by cyclic AMP. These effects might be obtained because of a direct competition between ADH and PGE2 for receptor binding on basolateral membranes. Alternatively, PGE2 might have reduced the affinities between ADH-receptor units and a component(s) of the series of processes leading to adenyl cyclase activation. The latter argument requires that basolateral membranes of the mouse mTALH exhibit receptor reserve, i.e., at the minimum concentration of ADH required to enhance Ve and JnetCl maximally, a fraction of basolateral membrane ADH receptors were unoccupied. According to this view, increasing peritubular ADH concentrations might reverse the PGE2-mediated reduction in ADH-dependent salt transport by increasing the number of basolateral membrane receptors occupied by ADH.

NaCl transport in mouse medullary thick ascending limbs. I. Functional nephron heterogeneity and ADH-stimulated NaCl cotransport.

We assessed the effects of antidiuretic hormone and cyclic adenosine monophosphate (cAMP) analogues on transepithelial voltage, Ve, and/or net chloride absorption in isolated mouse medullary (mTALH) and cortical (cTALH) thick ascending limbs of Henle; the passive NaCl permeability characteristics and electrical properties of the mTALH; and the effects of anion and cation substitutions and transport inhibitors on both basal and ADH-stimulated Ve and/or net chloride absorption in the mTALH. The data demonstrate that these two segments are functionally heterogeneous: ADH, at concentrations comparable to plasma levels seen in mammalian species during ordinary antidiuresis, and/or cAMP increase three- to fourfold the rate of NaCl absorption in the mTALH but not in the cTALH. The ion substitution and inhibitor data are consistent with the view that NaCl absorption in the mTALH depends on a secondary active transport process: NaCl entry across luminal membranes is a coupled process of indeterminate stoichiometry that is driven by the transmembrane electrochemical gradient for Na+, which is maintained by Na+-K+-ATPase. Finally, the data demonstrate that the mTALH is electrically leaky whether measured electrically, 11 omega . cm2, or isotopically, 50 omega . cm2, but essentially water impermeable; and that the mTALH is perm-selective for Na+ with respect to Cl-. The disparity between electrical resistances measured directly with respect to those calculated from tracer fluxes, together with the hybrid characteristics of mTALH junctional complexes (leaky to Na+ and Cl-; tight to water), may be reconciled by assuming that mTALH junctional complexes contain passive ion permeation pathways composed of narrow channels through which ions pass in single-file fashion.