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S Garella

Publications and source records attributed to S Garella.

At least 19 recordsLinked to original sources

The costs of dialysis in the USA.

End-stage renal disease (ESRD) is unique in that, in the United States, it is the only disease-specific condition covered by Medicare independently of the age of patients. Medical care to these patients is provided through 2506 facilities, most of which are free-standing. Of these, the majority are operated by profit-making concerns. The total number of patients served by the Medicare ESRD programme has increased each year and in 1995 it is estimated to be approximately 260,000, of which 195,000 are treated with maintenance dialysis, largely in-centre haemodialysis. Total expenditures for the ESRD programme (of which Medicare is responsible for approximately 72%) in 1995 are projected at $12.3 billion, of which Medicare is responsible for approximately $8.9 billion. Close to 50% of the expenditures are related to the provision of maintenance dialysis. The major component of these expenses is attributable to the Medicare 'composite' reimbursement fee, a fee the amount of which is established by Medicare to reimburse dialysis units for the provision of maintenance dialysis, independent of the costs that the unit might incur. This 'composite' fee has decreased substantially in the course of the last 20 years. The mortality of patients on dialysis in the USA remains high. This is in part due to the increasing severity of associated illnesses and more advanced age of the patients. However, the dose of delivered dialysis in the USA remains less than that observed in other industrialized countries. Three factors appear to play important roles in keeping the dose of dialysis low: the Medicare reimbursement method, the fiscal pressure on dialysis units to generate revenues, and patient preferences. There is general agreement that an increase in dialysis dose will be necessary to reduce mortality. However, this increase would be accompanied by increased costs to the providers of treatment. Improvements in the dose of dialysis to patients (and hence, it is hoped, in morbidity and mortality) are not likely to occur unless Medicare reimbursement increases and is designed to provide financial inducements to improve care and outcomes.

Costs and Cost Analysis

Drug-induced renal disease.

Many pharmacologic agents affect the kidney, but special attention should be paid to four classes: aminoglycoside antibiotics, radiocontrast agents, ACE inhibitors, and NSAIDs. Iatrogenic complications associated with these agents include acute renal failure, acute interstitial nephritis, and prerenal failure, which are frequently reversible with early diagnosis.

Acute Kidney Injury

Nonthrombocytopenic purpura associated sequentially with nifedipine and diltiazem.

OBJECTIVE: To report the case of a patient who developed nonthrombocytopenic purpura sequentially following the administration of nifedipine and diltiazem. DATA SOURCES: Case reports, MEDLINE review of pertinent literature, and review of relevant studies. DATA EXTRACTION: Data were extracted from direct patient observation and review of laboratory studies and published reports. DATA SYNTHESIS: Nonthrombocytopenic purpura secondary to cutaneous vasculitis is a known, although rare, adverse effect of nifedipine. It has not been reported in association with diltiazem. We report the case of a 75-year-old woman in whom a purpuric rash demonstrated by biopsy to be attributable to cutaneous vasculitis developed in the course of nifedipine therapy. The rash disappeared after discontinuation of the drug; however, it recurred when diltiazem therapy was initiated. CONCLUSIONS: Nonthrombocytopenic purpura may be associated with diltiazem as well as with nifedipine. When this adverse effect occurs following administration of a calcium-channel blocker, caution is advised in using other agents of the same class.

Aged

Chloride-depletion metabolic alkalosis induces ECF volume depletion via internal fluid shifts in nephrectomized dogs.

We recently reported that chloride-depletion metabolic alkalosis (CDMA) results in renal losses of Na, K, and water. In these studies we investigated whether CDMA (induced using a new model that avoids external changes in Na and water balance) was also associated with internal Na and water shifts out of the ECF. CDMA was induced using haemofiltration in functionally nephrectomized dogs. Plasma ultrafiltrate was substituted quantitatively with a solution duplicating each dog's plasma electrolyte composition in control animals, and with a solution containing HCO3 as the sole anion in CDMA animals. ECF volume was estimated as the space of distribution of [3H]-mannitol. Plasma composition and [3H]-mannitol distribution space were unchanged in control dogs. In CDMA dogs metabolic alkalosis developed; despite the absence of external changes in Na and water balance, the space of distribution of [3H]-mannitol decreased by 335 +/- 46 ml (equivalent to 8% of baseline ECF volume), calculated chloride space fell by 304 +/- 50 ml, and haematocrit increased from 45.6 to 48.5 vol%. We conclude that CDMA causes an internal shift of fluid out of the ECF. The resulting ECF volume contraction appears to be an inherent feature of CDMA.

Alkalosis

Acute interstitial nephritis with glomerulopathy due to nonsteroidal anti-inflammatory agents: a review of its clinical spectrum and effects of steroid therapy.

We reviewed case reports of patients who developed acute renal failure and/or nephrotic range proteinuria in the course of receiving treatment with nonsteroidal anti-inflammatory agents (NSAIA). Those cases that contained information sufficient to confirm the diagnosis of acute interstitial nephritis with glomerulopathy (AING), including a suggestive clinical syndrome with appropriate renal biopsy findings, were further analyzed to achieve a more complete description of this clinical entity and its responsiveness to steroid treatment. Analysis of the cases that fulfilled the inclusion criteria confirmed that the disorder is twice as common in women and occurs mainly in elderly people, usually after long-term use of NSAIAs for musculoskeletal problems. Fenoprofen was implicated in 47% of the cases. Evidence of systemic hypersensitivity was uncommon. Two thirds of the cases displayed clinical and/or histological evidence of both acute interstitial nephritis and increased glomerular permeability. These findings strongly suggest that this condition is distinct from other drug-induced "allergic" acute interstitial nephritides. In the absence of complicating factors, all patients improved following discontinuation of the offending agents. No evidence was found to suggest that steroid therapy altered the clinical course of this process.

Age Factors

Transport and histochemical studies of bicarbonate handling by the alligator kidney.

The alligator excretes a persistently alkaline urine despite consuming an acid-residue diet. The amount of bicarbonate excreted is greater than the amount filtered, evidencing tubular secretion of bicarbonate. The parallel urinary excretion of ammonium maintains external acid balance. To investigate putative renal mechanisms responsible for the concurrent excretion of large quantities of ammonium bicarbonate, we used acridine orange fluorescence methodology in microvesicles prepared from the proximal tubule brush border to assess the activity of the Na+-H+ antiporter, and histochemical methods (cobalt sulfide precipitation) to assess carbonic anhydrase localization. We found no evidence for the presence of a functioning Na+-H+ antiporter, the protein known to be responsible for the majority of bicarbonate reabsorption in mammals; Na+-H+ exchange in vesicles from the alligator kidney failed to exhibit saturation kinetics, showed no affinity for lithium, and was not inhibited by amiloride. Sensitive histochemical techniques failed to reveal carbonic anhydrase activity anywhere in the proximal tubule but detected an abundance of enzyme activity in the basolateral membranes and nuclei of distal tubular cells. In the connecting segment and collecting duct, cells without carbonic anhydrase alternated with cells containing carbonic anhydrase; in the latter, the enzyme was localized to the basolateral and luminal membranes, the nucleus and, to a lesser extent, throughout the cytoplasm. We conclude that the proximal tubule of the alligator kidney is devoid of the machinery necessary for the transport of large amounts of bicarbonate. The principal site at which bicarbonate is added to the final urine appears to be the distal tubule, at which site carbonic anhydrase is widespread.

Alligators and Crocodiles

Substitution of calcium carbonate for aluminum hydroxide in patients on hemodialysis. Effects on acidosis, on parathyroid function, and on calcemia.

Substitution of calcium carbonate for aluminum hydroxide in patients on dialysis: effects on acidosis, parathyroid function, and calcemia. We studied the effects of substituting CaCO3 for aluminum-containing gels on metabolic acidosis and on the response of the parathyroid glands in 11 patients treated with chronic hemodialysis. The 8 men and 3 women were clinically stable, were known to be compliant, and had no clinical evidence of aluminum overload; they were not receiving vitamin D supplements; and they had been on dialysis for an average of 65.6 months (range: 13-188 months). After 3 weeks of CaCO3 administration plasma phosphate concentration remained well controlled, and plasma calcium concentration increased from 9.2 +/- 0.2 (2.3 +/- 0.1 mmol/l) to 10.1 +/- 0.2 mg/dl (2.5 +/- 0.1 mmol/l). Predialysis plasma bicarbonate concentration increased from 19.7 +/- 0.6 to 21.9 +/- 0.6 mmol/l. Plasma aluminum concentration decreased from 78.7 +/- 12.5 to 48.5 +/- 3.9 micrograms/l. Plasma PTH level increased from 2.0 +/- 0.7 to 3.3 +/- 0.8 ng/ml despite the concurrent increase in plasma calcium levels. All values returned to control levels following discontinuation of CaCO3 and resumption of aluminum gels. We conclude: (1) In addition to controlling hyperphosphatemia and increasing plasma calcium concentration, CaCO3 ameliorates metabolic acidosis. (2) Avoidance of oral aluminum intake is followed by prompt lowering of plasma aluminum levels. (3) PTH levels paradoxically increase despite the increment in plasma calcium concentration. The hypercalcemia seen with CaCO3 administration may be due, in part, to transient parathyroid hypersecretion that develops when aluminum administration is discontinued.

Acidosis

Uremic acidosis.

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Acid-Base Equilibrium

Acidemia alone does not stimulate rat renal Na+-H+ antiporter activity.

To examine whether systemic acidemia is the cause of the adaptive increase in renal brush-border membrane (BBM) Na+-H+ exchange activity seen in metabolic acidosis, we examined the time course of changes in Na+-H+ exchange activity in rats with chronic metabolic or respiratory acidosis. Metabolic acidosis was created by allowing rats free access to a 1.5% NH4Cl drinking solution. Respiratory acidosis was created by housing rats in a chamber designed to maintain ambient PCO2 levels at 10%. All rats were fed normal rat chow. Control and respiratory acidosis rats had free access to tap water. Rats from each group were studied 1, 3, 5, 7, and 14 days after onset of treatment. Na+-H+ exchange activity was examined in renal BBM vesicles using acridine orange. In both metabolic acidosis and respiratory acidosis, arterial blood [H+] increased markedly at day 1 and returned toward normal thereafter; at day 14, [H+] was elevated to a comparable degree in both groups. In metabolic acidosis, Na+-H+ exchange activity remained at control levels for 3 days but increased markedly thereafter. In contrast, in respiratory acidosis no adaptive increase in activity occurred at any time. Because no correlation was found between blood [H+] and renal BBM Na+-H+ exchange activity, we conclude that stimuli other than systemic acidemia are responsible for the adaptation seen in chronic metabolic acidosis.

Acidosis

Renal response to metabolic alkalosis induced by isovolemic hemofiltration in the dog.

We describe a new model of chloride-depletion alkalosis (CDMA), in which the method of induction of alkalosis does not itself cause a direct alteration in sodium and fluid balance. We have used this model, which is based on hemofiltration techniques in the dog, to study the immediate response of the kidney to the induction of CDMA. Normal dogs maintained with a NaCl-free diet for several days underwent hemofiltration of 50 ml/kg over a 35 minute period. The hemofiltrate was replaced ml for ml with a solution containing sodium and potassium in the same concentrations as found in each animal's plasma water. In control animals, the replacement solution contained chloride and bicarbonate in the same ratio as in the plasma; in the experimental (CDMA) animals the replacement solution contained bicarbonate as the only anion. In the control group, the procedure of hemofiltration coupled with isovolemic replacement caused no appreciable changes in plasma composition, urinary excretion rates, GFR, or tubular handling of bicarbonate. In the CDMA group, 106 +/- 8.4 mEq of chloride were removed in exchange for bicarbonate. A marked metabolic alkalosis resulted, plasma bicarbonate concentration increasing from 21.9 +/- 0.6 to 33.3 +/- 0.6 mEq/liter. The hemofiltration procedure itself, by design, did not alter sodium or fluid balance. Nevertheless, cumulative urinary sodium excretion increased over 2.5 hours by 23.0 +/- 6.4 mEq. A natriuresis of this magnitude is equivalent to a loss of ECF volume of approximately 200 ml. GFR did not change significantly. The rate of tubular reabsorption of bicarbonate increased significantly from 1209 +/- 82 to 1559 +/- 148 mu Eq/min in CDMA animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Alkalosis

Immunopathologic mechanism of glomerular injury--an overview of current concepts.

It is now firmly established that a variety of immune mechanisms are responsible for most glomerulonephritides, and that they act largely through the activation of complement, recruitment of leukocytes and macrophages, stimulation of clotting, and liberation of vasoactive kinins. The etiological factors which originate the process can be either infectious agents, endogenous antigens (DNA, tumoral antigens), or exogenous toxins. The activation of the immune system may take different forms, including: the production of anti-GBM antibodies which may at times cross-react with other tissues or organs; the formation of antigen-antibody complexes of specific solubility, molecular size, permeability, which will variously tend to localize in the mesangium, in subepithelial, or subendothelial deposits; the development of antibodies which specifically react with native antigens present in the GBM in a discontinuous manner; the trapping of antigens within the GBM, which then act as "planted" antigens. The morphologic type of glomerulonephritis and its clinical course will probably depend upon the predominant type of antigen produced, its persistence, its mode of action, and the concurrent degree of activation of complement, recruitment of PMNs and macrophages, stimulation of the clotting system, as well as upon the development of hypertension and the functional response of the kidney to reduced renal mass. Whether or not it will be possible, in the future, to relate directly each type of glomerulonephritis to specific etiologic agents, to the type of immune response, and to genetic predisposition is unclear, but this will determine whether it will be possible to devise specific treatment strategies for each condition.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Effect of acute hypercapnia on renal bicarbonate reabsorption in the dog.

The increased plasma bicarbonate concentration seen in hypercapnia implies that tubular bicarbonate reabsorption must be increased in the presence of an elevated Paco2. In contrast to early reports, more recent experimental data in acute hypercapnia have been interpreted to show that the observed increment in tubular reabsorption of bicarbonate factored for glomerular filtration rate (THCO3/GFR) is largely related to the concurrent changes in renal sodium reabsorption and to the increment in the filtered load of bicarbonate, and that acute hypercapnia per se causes little or no change in the tubular handling of bicarbonate. We reexamined this question by observing the changes in renal function occurring in the presence of a moderate elevation of plasma bicarbonate concentration in two groups of dogs. In group I, the elevation occurred as a result of acute hypercapnia during the administration of an "isometric" solution; in group II, it was caused by the infusion of identical amounts of an isotonic solution with the same concentration of sodium as in group I, but a higher bicarbonate concentration, in the presence of eucapnia. A subset of group II provided controls for the decrease in renal perfusion pressure that occurred spontaneously in group I. With increasing filtered loads of bicarbonate, fractional excretion (FE) of HCO3 increased in group II, whereas it dropped markedly in group I. Furthermore, the relative reabsorption rate of HCO3 compared with that of Cl (assessed by changes in fractional reabsorption (FR) of HCO3/Cl) decreased in group II, whereas it increased in group I. Although FENa also decreased in group II, the opposite changes in FR(HCO3/Cl) could not be attributed solely to concurrent changes in sodium handling, indicating that in the presence of acute hypercapnia there is a preferential reabsorption of bicarbonate that tends to perpetuate the increase in plasma bicarbonate concentration. By contrast, THCO3/GFR rose in both groups. The data are interpreted to reveal that acute hypercapnia, although causing a drop in renal perfusion pressure and in natriuresis, also has an additional specific effect on raising preferential bicarbonate reabsorption. This effect can be detected best by monitoring changes in the anionic composition of tubular reabsorbate, whereas it may not be unveiled by following changes in THCO3/GFR. Changes in THCO3/GFR may not yield useful information regarding the integrated response of the kidney to acid-base perturbations, and the conclusions of previous studies based on changes in this parameter must be carefully reexamined.

Absorption

Renal effects of prostaglandins and clinical adverse effects of nonsteroidal anti-inflammatory agents.

Non-steroidal anti-inflammatory agents ( NSAIA ) are increasingly used in clinical practice. They exert the majority of their therapeutic and adverse effects by inhibiting prostaglandin synthesis. A variety of clinically important side effects have been described following their administration. We review the renal complications, which include sodium retention, interference with the effectiveness of diuretics, impairment of water excretion, development of hyperkalemia, interference with the therapy of hypertension, and induction of at least four different forms of renal failure. The hemodynamic variety of renal failure and the side effects affecting fluid and electrolyte homeostasis are most likely to become manifest in the context of conditions leading to decreased renal perfusion. Guidelines for use of NSAIA , detection of patients at risk, and therapeutic approaches are provided.

Acute Kidney Injury

Renal tubular acidosis associated with vitamin D-resistant rickets. Role of phosphate depletion.

3 children with vitamin D-resistant rickets (VDRR), and severe phosphate depletion had moderate metabolitic acidosis and evidence of impaired distal tubular acidifying mechanisms. Therapy with 1-alpha-OH-vitamin D3 and phosphate supplementation improved the clinical and radiological rachitic manifestations, and resulted in the normalization of systemic acid-base parameters as well as of tubular acidification. Profound phosphate depletion is another cause of acquired, reversible distal renal tubular acidosis (RTA).

Acidosis, Renal Tubular