Acute renal failure: outcomes and risk of chronic kidney disease.

Acute renal failure (ARF) is a common condition, especially among the critically ill, and confers a high mortality. The incidence of ARF is increasing. Efforts such as the Acute Dialysis Quality Initiative (ADQI) are being undertaken to establish a consensus definition of ARF, and to distinguish between varying degrees of acute kidney injury that might confer a different prognosis. Data are emerging to allow comparison of the epidemiology of ARF across institutions internationally. There is ongoing recognition of the important interaction between ARF and chronic kidney disease and more information regarding recovery from ARF is available. Controversy exists regarding the optimal management of ARF. Recent publications emphasize the importance of timing and dose of renal replacement therapy rather than the modality of treatment (intermittent hemodialysis vs continuous therapies). These issues are explored in this review.

The significance of the attachment of rat kidney glutaminase to the inner mitochondrial membrane.

The inner mitochondrial membrane of rat kidney mitochondria was altered by 0.03% Triton X-100 treatment in such a way as to render it permeable to NAD and CoA molecules without release of phosphate-dependent glutaminase. A break of linearity in the Arrhenius plot of the enzyme activity was characteristic for a conformational change of a membrane-bound enzyme. The activity of phosphate-dependent glutaminase immobilized in the inner mitochondrial membrane, as studied in 0.03% Triton X-100-treated mitochondria, and solubilized, as in the supernatant of sonicated mitochondria, was hyperbolic with respect to glutamine concentration. Under optimal conditions (pH 8.6 and 100 mM phosphate) the Vmax and Km were 216 +/- 12 nmol/mg per min and 2.7 +/- 0.4 mM, respectively, for Triton X-100-treated mitochondria, and 121 +/- 8 nmol/mg per min and 15.9 +/- 1.8 mM for sonicated mitochondria. Under near physiological conditions (pH 7.8 and 20 mM phosphate), distinct differences in phosphate-dependent glutaminase kinetics were observed. The Vmax as 29.8 +/- 0.4 and 2.6 /- 0.3 nmol/mg per min and the apparent Km 1.55 +/- 0.06 and 24.5 +/- 6.6 mM for Triton X-100 and sonicated mitochondria, respectively. The sigmoidal activation by phosphate at pH 7.8 was significantly shifted to the left in Triton X-100-treated as compared to sonicated mitochondria. As opposed to the data obtained in sonicated mitochondria, the kinetics of phosphate-dependent glutaminase in 0.03% Triton X-100-treated mitochondria agreed quite well with those obtained in intact, rotenone-inhibited and metabolically active mitochondria. These results suggest that an attachment of phosphate-dependent glutaminase to the inner membrane of kidney mitochondria has a profound effect on its kinetics, particularly under near physiological conditions.

Effect of imidazole on renal gluconeogenesis.

The metabolic effects of imidazole were tested in rat renal cortex. Imidazole enhanced the activity of renal cortical phosphodiesterase in vitro. Imidazole inhibited glucose production in a dose-dependent fashion from a variety of substrates in the gluconeogenic pathway proximal to the triose phsophates. The stimulation in renal gluconeogenesis resulting from isoproterenol and parathyroid hormone was inhibited by imidazole. These changes correlated with an inhibition of the augmented levels of renal cortical cyclic AMP levels produced by these hormones. These studies indicate that imidazole is an effective activator of phosphodiesterase in intact renal cells and lend further support to the suggestion that the stimulation of renal gluconeogenesis produced by isoproterenol and parathyroid hormone is mediated by a release of cyclic AMP.

Additive nephrotoxicity from roentgenographic contrast media. Its occurrence in phenazopyridine-induced acute renal failure.

A 68-year-old woman had reversible nonoliguric acute renal failure and yellow pigmentation of her skin and sclerae after ingesting phenazopyridine hydrochloride, 200 mg four times a day for six weeks. Although she began to recover renal function promptly after the drug therapy was discontinued, there was a further decline in her glomerular filtration rate after an oral cholecystogram and intravenous pyelogram. Phenazopyridine-induced acute renal failure is rare, but its early recognition is important so that additional nephrotoxicity from studies using roentgenographic contrast material may be avoided in patients with this problem.

Nephrosclerosis postpartum and in women taking oral contraceptives.

The condition of a patient with postpartum nephrosclerosis improved during heparin therapy. Review of the literature disclosed 29 other patients with the same histopathologic characteristics, eight of whom also recovered substantial renal function after anticoagulation therapy. Also reported is a patient in whom renal failure occurred while she was taking oral anovulatory agents. Renal biopsy specimen showed the same histopathologic features, which raises the question of similar factors mediating the expression of this disease. We suggest a uniform terminology for this syndrome, either postpartum nephrosclerosis or nephrosclerosis in women taking oral contraceptives.

Evidence that high dose cortisol-induced Na+ retention in man is not mediated by the mineralocorticoid receptor.

We have previously shown that high dose cortisol (F; 240 mg/day)-induced Na+ retention and systolic blood pressure (BP) increases are not inhibited by the glucocorticoid (type II) receptor antagonist RU486. Adequacy of type II receptor blockade with RU486 was clearly demonstrated, indicating that the Na+ retention was not mediated through the glucocorticoid receptor. Spironolactone (Sp: 400 mg/day), in a preliminary assessment, also did not inhibit F-induced Na+ retention. The purpose of this study was to determine whether the Na+ retention produced by F administration is mediated by the type I receptor by comparing the effects of F to a potent type I agonist [9 alpha-fludrohydrocortisone (9 alpha FF)] with and without Sp administration. The effects of the two agonists and Sp on urinary K excretion and BP were also compared. Normal male volunteers, on a constant daily diet for 10 days, received either F (240 mg/day) or 9 alpha FF (3.0 mg/day) with or without Sp (400 mg/day) for the last 5 days. The mean cumulative reductions in Na+ excretion during the 5 days compared to baseline values before hormone administration were 255 +/- 38 and 494 +/- 81 mmol/5 days for F (n = 9) and 9 alpha FF (n = 5), respectively (P = 0.01). Sp (n = 5) completely inhibited 9 alpha FF-induced Na+ retention (494 +/- 81 vs. -37 +/- 130 mmol/5 days; P less than 0.01), but had no effect (n = 5) on F-induced Na+ retention (255 +/- 38 vs. 193 +/- 50 mmol/5 days; P = NS). After the expected first day kaliuresis, the effects of both steroids on net cumulative urinary K+ excretion were minimal. Systolic BP was increased by F, but not 9 alpha FF, and Sp did not inhibit this increase. A 2-fold greater Sp-inhibitable Na(+)-retaining effect of the mineralocorticoid demonstrates that the failure of Sp to block F-induced Na+ retention is not due to inadequate type I receptor blockade. Based on these findings and earlier studies, we conclude that high dose (stress level) F-induced Na+ retention and systolic BP increase are not mediated by either the mineralo- or glucocorticoid receptor in normal man.

Perianeurysmal retroperitoneal fibrosis. An unusual cause of renal failure.

Retroperitoneal fibrosis causing ureteral obstruction in association with an abdominal aortic aneurysm has been reported infrequently. However, the clinical presentation of patients with this entity and the histopathologic findings at surgery are similar to those in patients with idiopathic retroperitoneal fibrosis. We describe a patient with perianeurysmal fibrosis and bilateral ureteral obstruction who presented with severe renal failure. The diagnosis of an abdominal aortic aneurysm with perianeurysmal fibrosis was made only at the time of surgery to repair bilateral ureteral obstruction. Previous case reports of perianeurysmal fibrosis are reviewed, and possible pathogenetic mechanisms are discussed. It is important to consider the presence of an occult abdominal aortic aneurysm in patients suspected of having retroperitoneal fibrosis because of the serious prognostic and therapeutic implications.

Cefoperazone for empiric therapy in patients with impaired renal function.

Thirty-five patients with serious infections and impaired renal function were treated empirically with 2 to 8 g of cefoperazone per day. Infections included sepsis in 14, nonbacteremic urinary infections in nine, pneumonia in five, intra-abdominal infection in five, fasciitis in one, and malignant otitis externa in one. The average age of this group was 64.3 years, 25 had ultimately fatal underlying diseases, and their average serum creatinine level was 5.2 mg/dl. Infections were caused by Enterobacteriaceae in 23 patients, Streptococcus faecalis in five, Pseudomonas aeruginosa in four, Staphylococcus aureus in four, Hemophilus influenzae in three, and Staphylococcus epidermidis, Streptococcus pneumoniae, and Clostridium sordelli in one each. Overall, 32 patients had clinical and microbiologic cures, two had improvement, and one had failure. Hypoprothrombinemia occurred in 18 of 28 patients not given vitamin K for prophylaxis and occurred more often in those with serum albumin concentrations below 3.5 g/dl. Prothrombin times returned to normal within 36 hours of treatment with vitamin K, although two patients experienced mild hematemesis. In anicteric patients with liver function abnormalities, 2 g every 12 hours produced peak and trough serum concentrations that averaged 254 and 125 micrograms/ml, respectively, compared with 179.5 and 19.5 micrograms/ml, respectively, in five with normal liver function test results. In jaundiced patients treated with 1 g every 12 hours, trough concentrations were comparably elevated. Serum concentrations did not correlate with hypoprothrombinemia, but high levels throughout the dosing interval may have contributed to the excellent cure rate in this study.

Metastatic periosteal osteosarcoma causing cardiac and renal failure.

The case of a 25-year-old man who had periosteal osteogenic sarcoma with intravascular metastases in unusual locations is reported. The patient presented with acute renal failure, unilateral pulmonary edema, functional mitral stenosis, and low cardiac output. After successful surgical removal of a left atrial metastasis with subsequent improvement in cardiac output, renal function improved only transiently and urinary output varied markedly. At autopsy, metastatic osteogenic sarcoma was discovered within the lumen of the abdominal aorta obstructing both renal arteries. The case is the first report of a neoplasm metastatic to the aorta causing intermittent bilateral renal arterial obstruction; it illustrates the diagnostic difficulties presented by intravascular metastatic disease.

Mortality of acute renal failure after rupture of abdominal aortic aneurysms.

Acute renal failure of an abdominal aortic aneurysm is associated with an extremely poor chance of survival. We reviewed the cases of ruptured abdominal aortic aneurysm presenting between January 1, 1976 and June 1, 1979. Four patients developed oliguric acute renal failure and required hemodialysis. All patients survived despite multiple life-threatening complications. The prognosis for acute renal failure after ruptured abdominal aortic aneurysm is better than previously recognized.

Calcium and phosphorus in diet therapy of uremia.

Significant advances have been made in understanding the pathogenesis of renal osteodystrophy. Several factors play a role in the development of uremic bone disease, such as secondary hyperparathyroidism, PTH resistance at the level of bone, abnormalities in vitamin D metabolism, and factors contributing to extraosseous calcification. Through a better understanding of the pathogenetic mechanisms, a more rational approach to the dietary management of patients with chronic renal failure has been possible. In view of present knowledge, the following preventive and therapeutic interventions can be recommended: provision of liberal calcium intake in the diet, appropriate restriction of phosphorus intake, provision of potent vitamin D analogs, and close attention to the calcium-phosphorus product. With careful attention to these recommendations, the bone lesions of secondary hyperparathyroidism and osteomalacia may be minimized and even prevented.

PEPCK mRNA localization in proximal tubule and gene regulation during metabolic acidosis.

To identify the nephron segments expressing PEPCK in control and acidotic conditions, PEPCK mRNA was localized in rat kidney using the technique of reverse transcription and polymerase chain reaction (RT-PCR) in individual microdissected S1 S2, and S3 segments of the rat proximal tubule. In controls, the number of tubules expressing PEPCK mRNA was greatest in the S3 segment, moderate in the S2 segment, and least in the S1 segment of the proximal tubule. After NH4Cl feeding, strong signals for PEPCK mRNA were detected in all three proximal tubule segments. In situ hybridization demonstrated expression of PEPCK mRNA only in the medullary rays in controls. After NH4Cl, PEPCK mRNA was expressed throughout the cortex, confirming the RT-PCR results. These data demonstrate the ability of the rat kidney cortex to modulate the expression of PEPCK mRNA during metabolic acidosis by recruitment of additional cells in the proximal nephrons. Studies with cultured LLC-PK1-F+ cells indicated that increased PEPCK gene transcription at acid pH required a cis-acting element (enhancer) in the more distal 5' flanking region of the promoter.

Acute aluminum toxicity associated with oral citrate and aluminum-containing antacids.

The authors report the development of a rapidly progressive encephalopathy marked by confusion, myoclonus, seizures, coma, and death in a group of women with renal failure who received an oral solution of citrate and aluminum hydroxide gel concurrently. Two patients were documented as having marked hyperaluminemia far exceeding blood aluminum levels encountered in the chronic state of aluminum intoxication. We ascribe the toxicity to enhanced gastrointestinal absorption of aluminum when complexed with citrate.

Aluminum-citrate interaction in end-stage renal disease.

The influence of a sodium citrate/citric acid mixture on the gastrointestinal (GI) absorption of aluminum (Al) from an Al(OH)3 preparation was evaluated in six stable maintenance hemodialysis patients. Plasma Al concentrations were determined serially after each of the following treatment sequences (I) Al(OH)3; (II) Al(OH)3 + sodium citrate/citric acid; (III) sodium citrate/citric acid; (IV) Al(OH)3 + NaHCO3. AUC0-8 for plasma Al from 0 to 8 hours was significantly greater (p less than 0.05) for Al(OH)3 + sodium citrate/citric acid (73 +/- 23 micrograms.hr/l; mean +/- SEM) than Al(OH)3 (16 +/- 30 micrograms.hr/l); sodium citrate/citric acid (-27 +/- 14 micrograms.hr/l); or Al(OH)3 + NaHCO3 (6 +/- 22 micrograms.hr/l). The 24 hour Al level remained above baseline (p less than 0.03) following Al(OH)3 + sodium citrate/citric acid (31 +/- 12 (pre) vs 54 +/- 14 micrograms/l (post), in contradistinction to study limb: l (34 +/- 14 vs 30 +/- 12 micrograms/l); III (79 +/- 40 vs 65 +/- 35 micrograms/l); and IV (71 +/- 37 vs 66 +/- 42 micrograms/l). We conclude that the GI absorption of Al from Al(OH)3 is enhanced by citrate in patients undergoing hemodialysis and that elevations of plasma Al persist longer. The concomitant administration of citrate and Al-containing phosphate (PO4) binders should be avoided in patients with end-stage renal disease (ESRD). NaHCO3 may serve as an alternative therapy for metabolic acidosis with less risk of enhancing Al absorption.