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Biomedical subjects

R D Toto

Publications and source records attributed to R D Toto.

At least 37 records · Page 2Linked to original sources

Renal insufficiency due to angiotensin-converting enzyme inhibitors.

Angiotensin-converting enzyme (ACE) inhibitors represent a major therapeutic breakthrough for treatment of hypertension, congestive heart failure and various chronic renal diseases. They are effective generally well tolerated and safe for most patients. However, acute renal insufficiency or overt renal failure occurs in some patients with underlying critical renal artery stenosis (RAS), hypertensive nephrosclerosis, autosomal dominant polycystic kidney disease, diabetes mellitus, and chronic congestive heart failure. Diuretic-induced sodium depletion and underlying chronic renal insufficiency are the major predisposing factors for renal insufficiency in all of these patient populations. Renal insufficiency is usually asymptomatic, nonoliguric, associated with hyperkalemia, and in nearly every case completely reversible after discontinuation of the offending agent. Moreover, it can usually be managed in the outpatient setting by discontinuation of the ACE inhibitor, concomitant diuretic or both. An asymptomatic increase in serum creatinine in patients administered ACE inhibitors should raise the possibility of RAS; however, more common renal diseases should be considered. The decision to pursue testing for RAS should be done on an individual basis; moreover, it is imperative that patient willingness to undergo invasive procedures including angioplasty and/or surgery should be determined prospectively.

Acute Kidney Injury↗

Gentamicin clearance during hemodialysis: a comparison of high-efficiency cuprammonium rayon and conventional cellulose ester hemodialyzers.

The advent of high-efficiency hemodialyzers has afforded improved efficiency of urea clearance; however, increased clearance of other substances, particularly antibiotics, also may occur, necessitating changes in clinical practice. Accordingly, we compared the efficiency of gentamicin removal using two different hemodialyzers, a conventional saponified cellulose ester (CD 135) and a high-efficiency cuprammonium rayon dialyzer (TAF 175L), in eight hospitalized patients undergoing antibiotic therapy for suspected or proven gram-negative infection. The rate of dialysis, estimated as the ratio of dialyzer urea clearance (K) to urea distribution volume (V) (K/V urea), and the total elimination rate constant (k) of gentamicin were measured during 17 hemodialysis treatments. The K/V urea for the two dialyzers, TAF 175L and CD 135, was 0.390 +/- 0.024 hr-1 and 0.413 +/- 0.129 hr-1 (P = NS), respectively. The TAF 175L hemodialyzer was almost twice as efficient in removing gentamicin as the CD 135: TAF 175, k = 0.263 +/- 0.024 hr-1; CD 135, k = 0.132 +/- 0.027 hr-1 (P < 0.001). Moreover, the rate of dialysis (K/V urea) was correlated with k of gentamicin for the TAF 175L dialyzer (r2 = 0.50, P < 0.02) but not for the CD 135 dialyzer. We conclude that dialyzer characteristics and the rate of dialysis (K/V urea) should be taken into consideration when determining the dosage of gentamicin in patients on hemodialysis.

Adult↗

Mechanisms and treatment of dyslipidemia of renal diseases.

Dyslipidemia is commonly observed in nephrotic syndrome, in chronic renal failure, and after renal transplantation. The patterns of dyslipidemia, however, differ among these three conditions, and the origins and mechanisms responsible for abnormalities in lipoprotein metabolism in each are not well understood. Whether these dyslipidemias contribute to the development of atherosclerosis and coronary heart disease is uncertain, but it is probable that they do. Important questions are whether an attempt should be made to treat the various renal dyslipidemias, and if so, by what means. Also of current interest are dyslipidemias in the nephrotic syndrome, chronic renal failure (uremia), and the post-renal transplantation state.

Animals↗

Tumor lysis syndrome.

Tumor lysis syndrome is a critical illness characterized by massive tumor cell death leading to severe hyperuricemia, hyperphosphatemia, hyperkalemia, hypocalcemia, and acute renal failure in patients with rapidly growing cancers (especially Burkitt's lymphomas with extensive abdominal bulk). It may be preventable with allopurinol therapy combined with aggressive intravenous fluid therapy aimed at establishing an ongoing alkaline diuresis. In most cases renal failure is completely reversible; however, fatal hyperkalemia and volume overload may develop. Therefore, aggressive management with hemodialysis often is necessary to maintain life support while tumor burden is controlled with cytoreductive therapy. Early recognition and management by a team approach in the intensive care unit where careful monitoring is available serves to forestall severe renal failure, thereby improving short-term prognosis in susceptible patients.

Adult↗

Sympathetic overactivity in patients with chronic renal failure.

BACKGROUND: Hypertension is a frequent complication of chronic renal failure, but its causes are not fully understood. There is indirect evidence that increased activity of the sympathetic nervous system might contribute to hypertension in patients with end-stage renal disease, but sympathetic-nerve discharge has not been measured directly in patients or animals with chronic renal failure. METHODS: We recorded the rate of postganglionic sympathetic-nerve discharge to the blood vessels in skeletal muscle by means of microelectrodes inserted into the peroneal nerve in 18 patients with native kidneys who were undergoing long-term treatment with hemodialysis (of whom 14 had hypertension), 5 patients receiving hemodialysis who had undergone bilateral nephrectomy (of whom 1 had hypertension), and 11 normal subjects. RESULTS. The mean (+/- SE) rate of sympathetic-nerve discharge was 2.5 times higher in the patients receiving hemodialysis who had not undergone nephrectomy than in the normal subjects (58 +/- 3 vs. 23 +/- 3 bursts per minute, P < 0.01). In contrast, the rate of sympathetic-nerve discharge was similar in the patients receiving hemodialysis who had undergone bilateral nephrectomy (21 +/- 6 bursts per minute) and the normal subjects. The rate of sympathetic-nerve discharge in the patients receiving hemodialysis who had not undergone nephrectomy was also significantly higher (P < 0.01) than that in the patients with bilateral nephrectomy, and it was accompanied in the former group by higher values for vascular resistance in the calf (45 +/- 4 vs. 22 +/- 4 units, P < 0.05) and mean arterial pressure (106 +/- 4 vs. 76 +/- 14 mm Hg, P < 0.05). The rate of sympathetic-nerve discharge was not correlated with either plasma norepinephrine concentrations or plasma renin activity. CONCLUSIONS: Chronic renal failure may be accompanied by reversible sympathetic activation, which appears to be mediated by an afferent signal arising in the failing kidneys.

Angiotensin II↗

Paradoxical withdrawal of reflex vasoconstriction as a cause of hemodialysis-induced hypotension.

Acute hypotension is an important complication of hemodialysis, but the underlying mechanisms remain poorly understood. Because hemorrhage-induced hypovolemia can trigger a sudden decrease in sympathetic activity resulting in bradycardia and vasodilation, we hypothesized that hemodialysis-induced hypovolemia also can trigger the same type of vasodepressor reaction, which would exacerbate the volume-dependent fall in blood pressure. We therefore measured blood pressure, vascular resistance, and sympathetic nerve activity (intraneural microelectrodes) during sessions of maintenance hemodialysis in 7 patients with and 16 patients without a history of hemodialysis-induced hypotension. During hemodialysis, blood pressure at first remained unchanged as calf resistance increased in both hypotension-resistant (from 37 +/- 4 to 49 +/- 5 U, P < 0.05) and hypotension-prone (from 42 +/- 6 to 66 +/- 12 U, P < 0.05) patients; sympathetic activity increased comparably in the subset of patients in whom it could be measured. With continued hemodialysis, calf resistance and sympathetic activity increased further in the hypotension-resistant patients, but in the hypotension-prone patients the precipitous decrease in blood pressure was accompanied by decreases in sympathetic activity, vascular resistance, and heart rate as well as symptoms of vasodepressor syncope. On an interdialysis day, both groups of patients increased vascular resistance normally during unloading of cardiopulmonary baroreceptors with lower body negative pressure and increased heart rate normally during unloading of arterial baroreceptors with infusion of nitroprusside. These findings indicate that in a group of hemodialysis patients without diabetes or other conditions known to impair autonomic reflexes, hemodialysis-induced hypotension is not caused by chronic uremic impairment in arterial or cardiopulmonary baroreflexes but rather by acute, paradoxical withdrawal of sympathetic vasoconstrictor drive producing vasodepressor syncope.

Adult↗

Reversible renal insufficiency due to angiotensin converting enzyme inhibitors in hypertensive nephrosclerosis.

OBJECTIVE: To review the incidence of reversible renal insufficiency in patients with hypertensive nephrosclerosis undergoing antihypertensive therapy. DESIGN: Retrospective analysis of 73 patients in a long-term blood pressure control study that compared the effects of an angiotensin converting enzyme (ACE) inhibitor plus conventional antihypertensive agents compared with placebo plus antihypertensive agents. SETTING: Hospital-based outpatient treatment center. INTERVENTIONS: Patients were divided into group 1, which received enalapril plus conventional antihypertensives, and group 2, which received placebo plus conventional antihypertensives. MEASUREMENTS: Blood pressure and serum creatinine levels were measured, and imaging studies of the main renal arteries were done. MAIN RESULTS: In group 1, eight of 42 patients (19%, 95% CI, 9% to 34%) developed reversible renal insufficiency, defined as an unexpected increase in serum creatinine of 88 mumol/L or higher. Six episodes of reversible renal insufficiency occurred during July and August when temperatures were 32.2 degrees C to 37.8 degrees C (90 degrees F to 100 degrees F). Renal artery stenosis was excluded by renal arteriogram or ultrasonic duplex scanning. All eight group-1 patients had a significant decrease in mean arterial pressure below their baseline level during reversible renal insufficiency (mean change, -28 +/- 10 mm Hg, P less than 0.001). The increase in the serum creatinine level was inversely correlated with the decrease in the mean arterial pressure (r = -0.68, P less than 0.01). Reversible renal insufficiency was successfully managed by withdrawing or reducing enalapril as well as other antihypertensive agents. Subsequently, enalapril was tolerated by seven of the eight patients without recurrence of renal insufficiency. In contrast, none of 31 (CI, 0% to 11%) patients in group 2 developed reversible renal insufficiency despite the fact that both the incidence of decreases in mean arterial pressure in 6 of 31 patients (19%) and the magnitude of the decreases in mean arterial pressure (mean change, -33 +/- 16 mm Hg) were similar to those observed in group 1. CONCLUSIONS: Reversible renal insufficiency in hypertensive nephrosclerosis associated with ACE inhibitor therapy correlates with relative hypotension, is not dependent on renal artery stenosis, and can usually be managed by dose reduction.

Aged↗

Severe neurologic toxicity induced by cyclosporine A in three renal transplant patients.

Cyclosporine A (CyA) is a potent immunosuppressive agent that is used in organ transplantation and in a variety of immunological diseases. It has a variety of adverse side effects, some of which can be serious and even life-threatening. CyA-associated neurotoxicity is generally mild, consisting of fine tremor. However, more complex neurologic abnormalities, including motor spinal cord and cerebellar syndromes, have rarely been described in bone marrow and liver transplant patients. Renal transplant patients have been spared from such CyA-induced toxicity. In this report, three renal transplant patients are described who developed complex and severe neurologic toxicity in the setting of therapeutic blood levels of CyA, which was completely reversible on discontinuation of the drug. No patient had a prior history of neurological or psychiatric dysfunction and there was no evidence of known psychoactive substance abuse. The toxicity was manifested as flaccid hemiparesis in one and dementia in a second patient. The third patient developed a previously unreported Guillain-Barré-like syndrome consisting of an ascending motor neuropathy. One patient developed reversible lesions involving the cerebral white matter. Whereas similar complex neurologic syndromes have been confined to patients who are intensely immunosuppressed, often debilitated, and have toxic levels of the drug, these three patients serve to emphasize that complex neurotoxicity can occur in stable patients who have therapeutic levels of CyA. Given the use of CyA in an ever-expanding list of disease processes, an appreciation of these potential neurologic syndromes is of paramount importance. At present, CyA-induced neurologic disease remains a diagnosis of exclusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

The role of prostaglandins in NSAID induced renal dysfunction.

Renal prostaglandins (PG) play an important role in regulating renal hemodynamics and excretory function in 2 conditions (1) which effective arterial blood volume is reduced and (2) chronic renal failure is reduced. The use of nonsteroidal antiinflammatory drugs (NSAID) in patients with these conditions can produce a significant decline in renal function, including decreased glomerular filtration rate and solute and water excretion, by inhibiting renal cyclooxygenase, and thus, PG production. Results of preliminary investigation with the PGE1 analog misoprostol suggest that exogenous PG analogs may be effective in counteracting the effects of NSAID in such settings. Further clinical studies will be needed to establish the role of PG in this setting.

Alprostadil↗

Acute tubulointerstitial nephritis.

Acute tubulointerstitial nephritis (ATIN) is a common disorder characterized by a spectrum of clinical manifestations ranging from asymptomatic urinary abnormalities to acute oliguric renal failure. Tubular dysfunction out of proportion to the degree of renal failure is an important clue to the diagnosis. This review describes its pathogenesis, pathophysiology, diagnosis, differential diagnosis and therapy, emphasizing the drug-induced form of ATIN.

Animals↗

Cardiorenal effects of atrial natriuretic factor administration in congestive heart failure: natriuresis and diuresis without hemodynamic alterations.

The effects of low bolus dose (70 +/- 6 micrograms [mean +/- SEM]) atrial natriuretic factor (ANF) administration was assessed in 16 patients with chronic congestive heart failure. Measurements were made for at least 60 minutes before and after the dose of ANF. There was a significant increase in urine flow rate (0.81 +/- 0.06 to 1.81 +/- 0.23 ml/min, p less than 0.01), sodium excretion rate (56 +/- 14 to 80 +/- 23 microEq/min, p less than 0.01), fractional excretion of sodium (1.23 +/- 0.49 to 1.63 +/- 0.60 percent, p less than 0.01) and potassium excretion rate (35 +/- 7 to 42 +/- 6 microEq/min, p less than 0.02). However, no significant alterations in renal plasma flow or glomerular filtration rate were observed. Furthermore, there was no significant correlation between the change in urine flow rate or sodium excretion rate and the change in renal plasma flow or glomerular filtration rate, respectively. In addition, there was no significant effect on cardiac index, mean aortic or left ventricular filling pressures, or systemic vascular resistance. There also was no discernible relationship between the response to ANF and the baseline concentrations of plasma ANF, aldosterone, or plasma renin activity. Thus, in patients with congestive heart failure, low dose ANF boluses may produce an increase in urine flow rate and sodium excretion rate that is independent of renal plasma flow or glomerular filtration rate. This suggests a meaningful direct renal tubular effect of exogenous ANF in this setting.

Adult↗

Confirmation of the utility of fine needle aspiration biopsy of the renal allograft.

Allograft immunobiologic theory would predict that analysis of immunocompetent cells infiltrating the renal transplant would be most instructive. Recently a new aspiration biopsy technique has been developed to permit such analysis in patients which can be safely and repetitively performed. The clinical utility of such a technique has been tested utilizing a randomized prospective trial in which an aspirate was obtained every other day from the third post-operative day until discharge. Analysis included examination of adequacy criteria and the capacity of pathologic diagnosis to corroborate clinical diagnosis from coded specimens. Ninety-six aspirates from 21 consenting transplant recipients were obtained and analyzed. In 94 instances a clinical diagnosis could be made; 80 aspirates fulfilled adequacy criteria. We found the technique to be highly sensitive (greater than or equal to 90%) and highly specific (greater than or equal to 90%) for the clinical diagnoses of acute allograft rejection, post-operative acute renal failure, cyclosporine toxicity, and normal function. We conclude that the fine needle aspiration technique is an important adjunct to analysis of clinical renal transplantation and offers a major advantage to the clinical scholar in understanding transplant biology.

Acute Kidney Injury↗

Carbonic anhydrase inhibitors.

The purpose of the present review is to describe the use of carbonic anhydrase inhibitors in clinical medicine and renal physiology. We first describe the localization of carbonic anhydrase within the kidney and then discuss evidence for its role in renal acidification and NaCl absorption. This is then followed by a description of clinical uses for carbonic anhydrase inhibitors. Many of the uses and effects of carbonic anhydrase inhibitors can be predicted from an understanding of renal physiology and the role of carbonic anhydrase. The limited potency of carbonic anhydrase inhibitors correlates well with the large magnitude of carbonic anhydrase-independent bicarbonate absorption. While theories for carbonic anhydrase-independent bicarbonate absorption are presented, the exact mechanisms remain unresolved.

Bicarbonates↗

Effects of nonsteroidal antiinflammatory drugs on renal function in patients with renal insufficiency and in cirrhotics.

We have assessed the effects of acute and chronic administration of etodolac, ketoprofen, and indomethacin on renal function in patients with mild to moderate chronic renal insufficiency (CRI). We studied 18 normal volunteers and 24 patients with CRI due to hypertension and/or diabetes mellitus with creatinine clearances between 19 and 83 mL/min/1.73 m2. Clearance studies were performed with the first dose of nonsteroidal antiinflammatory drug (NSAID) to compare acute effects of the agent with a no-drug control. Subjects then received the NSAID for three to five days and, on the last day of study, underwent another clearance study to assess the effects of a single dose of NSAID superimposed on chronic dosing. With each dose of each NSAID, inulin and paraaminohippurate (PAH) clearances and fractional excretion of NA+ decreased. However, the baseline control collections after chronic dosing did not differ from the no-drug control periods. Hence, the decline in renal function with each dose is transient, and no overall adverse effect on renal function occurred with chronic dosing. In five patients with cirrhosis, we assessed the renal sparing effects of sulindac. After equilibration on a fixed sodium intake, they received a 200-mg dose of sulindac. In one patient, no adverse effect occurred; the remaining patients suffered declines in creatinine clearance of 29%, 87%, 37%, and 37%, respectively. This effect was transient and returned to control values six to eight hours after sulindac administration. At the time of maximal depression of renal function, serum concentrations of sulindac sulfide were comparable to those in subjects with normal hepatic function.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetates↗

Effects of acute and chronic dosing of NSAIDs in patients with renal insufficiency.

Administration of nonsteroidal anti-inflammatory drugs (NSAIDs) to patients with chronically impaired renal function has been reported to cause abrupt and sustained reductions in renal plasma flow (RPF), glomerular filtration rate (GFR), and solute and water excretion in association with decreased renal prostanoid production. However, the time course of these acute effects and whether they are sustained during chronic exposure to the NSAIDs are unknown. Accordingly, using standard clearance and balance techniques, we investigated the effects of acute (zero to four hours) and chronic (five days) oral administration of two different NSAIDs on renal function in patients with stable, mild to moderate chronic renal insufficiency (CRI) and in normal subjects. In patients, acute oral administration of ketoprofen (K) and indomethacin (I) resulted in significant decreases in GFR (K: from 36 +/- 3 to 20 +/- 4 ml/min, P = 0.001; I: from 37 +/- 6 to 30 +/- 7 ml/min, P = 0.032; in RPF (K: from 194 +/- 21 to 146 +/- 21 ml/min, P = 0.002; I: from 222 +/- 33 to 147 +/- 18 ml/min, P = 0.016); and in urinary PGE2 excretion (K: from 0.60 +/- 0.25 to 0.08 +/- 0.02 ng/min, P = 0.05; I: from 0.34 +/- 0.06 to 0.18 +/- 0.06 ng/min, P = 0.042). Fractional excretion of sodium chloride and fractional free water clearance (CH2O/CIn) also decreased significantly after both agents. In normal subjects, GFR and RPF were not significantly decreased after acute dosing, whereas urinary PGE2 and fractional excretions of NaCl and free water decreased significantly.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Lack of a direct effect of atrial natriuretic factor in the rabbit proximal tubule.

Whole animal clearance studies and in vitro microperfusion studies were performed to examine the effect of atrial natriuretic factor (ANF) on the rabbit proximal tubule. Infusion of ANF into rabbits resulted in an increase in glomerular filtration rate and a natriuresis and diuresis. To determine whether ANF has a direct proximal tubule effect to account for part of the observed natriuresis, proximal convoluted tubules (PCT) and proximal straight tubules (PST) were perfused in vitro. Addition of 10(-9) M ANF, a concentration recently measured in vivo during volume expansion, to the bathing solution of PCT caused no significant change in volume absorption. Addition of a pharmacological concentration of ANF (10(-7) M) to either the bathing solution or the luminal perfusate of PCT resulted in no change in volume absorption. When added to the bathing solution of PST, 10(-7) M ANF did not have an effect on volume absorption. ANF did not affect the transepithelial potential difference in any protocol. In conclusion, these data show that ANF does not affect transport directly in the proximal tubule.

Animals↗