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PubMed1988

Angiotensin converting enzyme inhibitors. II. Clinical use.

Since their introduction in clinical practice in 1980, ACE inhibitors have been found useful in the treatment of hypertension and CHF. In hypertension, they are effective as monotherapy in 40% to 50% of the patients, and in combination with diuretics or calcium antagonists, they are effective in up to 85% of the patients. They are well tolerated, are not associated with depression, impotence, bronchospasm or metabolic derangements such as hypokalemia, hyperuricemia or hyperglycemia, and do not have adverse effects on the quality of life. As a result, they are preferred in hypertensive patients with CHF, left ventricular dysfunction, mental depression, older age, coronary artery disease, metabolic disorders, chronic destructive pulmonary disease, and peripheral vascular disease. In CHF they cause long-lasting hemodynamic and symptomatic improvement, improve exercise tolerance, and may lower mortality in certain patient subsets. Evolving new indications for ACE inhibitors include the diagnosis of renovascular hypertension, the prediction of surgical success, the treatment of scleroderma renal crisis, the reduction of proteinuria, renal protection, cardioprotection, the improvement of arterial compliance, in Bartter's syndrome and idiopathic edema, etc. ACE inhibitors are usually well tolerated but in some instances they may cause class-specific side effects such as hypotension; usually reversible azotemia or renal failure, especially in patients with renal artery stenosis or with CHF with low blood pressure; cough; angioedema; and hyperkalemia. Differences among ACE inhibitors are emerging and include chemical class (e.g., zinc ligand), biotransformation, potency, pharmacokinetics, prodrugs, tissue effects, additional pharmacologic properties, and drug interactions.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1989

Safety and efficacy of percutaneous transluminal coronary angioplasty performed at time of diagnostic catheterization compared with that performed at other times.

Performing diagnostic cardiac catheterization and percutaneous transluminal coronary angioplasty (PTCA) as a single, combined procedure might provide savings in patient hospitalization days and more efficient use of catheterization laboratory time. To assess the safety and efficacy of combined diagnostic coronary angiography and PTCA, we reviewed all elective PTCA procedures performed at our institution during 1985 and 1986 so that we could compare patients who had diagnostic angiography and angioplasty on separate days (n = 404) with those who had the combined procedure (n = 120). The success rate and incidences of urgent bypass surgery, acute myocardial infarction, transient azotemia and procedure-related death were not different in the 2 groups. The mean hospitalization time was 6.2 days in the group with combined angiography and angioplasty, and 7.3 days in the group having separate procedures.

Angiography↗

PubMed1975

Hypertension corrected by discontinuing chronic sodium bicarbonate ingestion. Subsequent transient hypoaldosteronism.

A 52 year old man with a long history of marked hypertension, peptic ulcer disease, nephrocalcinosis and intermittent hypercalcemia was referred to be evaluated for primary aldosteronism suspected on the basis of low plasma renin activity, hypokalemia and blood pressure responsive to spironolactone. Aldosterone excretion, however, was extremely low. Alkaluria, high urinary sodium excretion and hypercalciuria were observed. The patient admitted to chronic ingestion of large amounts of baking soda. Upon cessation of alkali abuse, his blood pressure fell dramatically; orthostatic hypotension, concomitant azotemia, hemoconcentration, hyperkalemia and weight loss occurred. Despite dramatic elevation in plasma renin activity, urinary aldosterone excretion remained low during this period. Adrenal glucocorticoid secretion was intact. All abnormalities of sodium, potassium and aldosterone subsequently returned to normal. A 10 day challenge with oral sodium bicarbonate was associated with a rise in blood pressure, but serum calcium remained normal. The patient remains normotensive 15 months after discontinuing alkali abuse.

17-Hydroxycorticosteroids↗

PubMed1976

Modern system for treating high blood pressure based on renin profiling and vasoconstriction-volume analysis: a primary role for beta blocking drugs such as propranolol.

A new system is proposed for treating the spectrum of patients with high blood pressure. It is based on studies of the renin axis using renin profiling, pharmacologic probes and our bipolar vasoconstriction-volume hypothesis. The new system does not require renin profiling, pharmacologic testing or a vasoconstriction-volume analysis for widespread application. But these procedures, whenever available, will make treatment more efficient and more certain, and at the same time provide better base line definition. In the new system, all patients, except the elderly and those with congestive heart failure, bradycardia or a history of asthma, are treated first with propranolol alone, a procedure which will diminish or normalize blood pressure in many patients with high and noraml renin levels. For nonresponders, diuretic therapy is then superimposed. Subsequently, a propranolol subtraction trial picks out the low-renin patients who will usually respond to a diuretic alone. This program is likely to be fully effective in possible up to 85 per cent of patients. For the residual smaller fraction, drugs such as hydralazine, methyl DOPA, clonidine, reserpine or guanethidine are then added in traditional trial and error fashion. The proposed system has the theoretic attraction for long-term commitment, implicit in antihypertensive therapy, of achieving blood pressure control in large fractions with one drug instead of two or with two drugs instead of three or more. Moreover, the large groups who respond to therapy with propranolol alone (most high-renin and normal-renin patients) or to diuretics alone (most low-renin patients) gain the advantage of simple, more specific, long-term (i.e., antirenin or antivolume) therapy. The use of propranolol alone has practical and theoretic advantages over diuretics. Control may be achieved with even fewer side effects and without hypokalemia and chronic dehydration with its possibly adverse consequences (hyperuricemia, azotemia, hyperlipidemia, hyperreninemia, increased blood viscosity). Also, propranolol provides more direct control of the increased peripheral resistance and of neurogenically-induced swings in blood pressure. At the same time, the new system efficiently exploits the long-term use of diuretic therapy alone in low-renin patients in whom volume excess seems a causal factor. And it tends to avoid the use of diuretics in high-renin patients and of beta-blockers in low-renin patients in whom these drug types may be contraindicated.

Adrenergic beta-Antagonists↗

PubMed1978

Sodium wasting, acidosis and hyperkalemia induced by methicillin interstitial nephritis. Evidence for selective distal tubular dysfunction.

A 61 year old male patient was studied who manifested dehydration, azotemia, acidosis and hyperkalemia six weeks after exposure to methicillin. Thyroid and adrenal glucocorticoid and mineralocorticoid function were normal. The dehydration was found to be caused by a profound sodium-losing nephropathy; urinary sodium ranged from 78 to 101 meq/day during a salt restricted diet. A distal renal tubular acidosis and a quantitively impaired ability to excrete potassium were also found. These defects were relatively unresponsive to mineralocorticoid or prednisone therapy. A renal biopsy specimen showed an interstitial nephritis which selectively affected distal tubules and was thought to be secondary to methicillin. The data suggest functional impairment specific for the distal tubule, but with only a modest decrease in the glomerular filtration rate.

Acidosis↗

PubMed1981

Light chain nephropathy.

In 13 specimens of renal tissue from 11 patients, deposits of monoclonal immunoglobulin light chains and continuous granular electron-dense material within tubular basement membranes and in association with the glomerular basement membrane were identified. All but one patient were men n the fifth to seventh decades of life, and each presented with azotemia and features of glomerular rather than tubulointerstitial disease. Osteolytic bone lesions occurred in only three patients, and a bone marrow plasmacytosis greater than 30 percent consistent with plasma cell myeloma was identified in only four patients. Light chain distribution in the nephron was confirmed with immunoelectron microscopy and was not associated with deposition of other serum proteins such as immunoglobulin heavy chains, complement, transferrin, alpha 2 macroglobulin and albumin. The electron dense deposits differed in distribution and character from those associated with membranoproliferative glomerulonephritis type II (dense deposit disease), amyloidosis, cryoglobulinemia, macroglobulinemia and benign monoclonal gammopathy. Serum from six of these patients did not bind to normal human or rat renal parenchyma in vitro. Kappa light chain nephropathy was characterized by predominant linear tubular basement membrane kappa deposits, and nodular mesangial and linear glomerular basement membrane kappa immunostaining. Lambda light chain nephropathy was characterized by linear lambda glomerular basement membrane and tubular basement membrane immunostaining. Manifestations of glomerular dysfunction dominated the clinical presentation of light chain nephropathy, and most patients did not have typical features of multiple myeloma. The diagnosis was predicated upon thorough immmunohistologic assessment of renal biopsy material.

Adult↗

PubMed1981

Renal manifestations of the staphylococcal toxic-shock syndrome.

Twenty-three women of ages 13 to 44 years were hospitalized with illnesses fulfilling the criteria of the case definition for the toxic-shock syndrome (TSS) associated with coagulase-positive staphylococci. Disease onset occurred during menses in 22, and all were oliguric when admitted. Prolonged hypotension and a reduced central venous pressure were common features. Measurements of urine volume and creatinine clearance in eight patients identified two types of acute renal failure, oliguric and nonoliguric, and prerenal azotemia related to intravascular volume depletion. Urinary sodium excretion and measurement of the renal index (UNa divided by U/PCr) provided further support for the presence of both prerenal and intrinsic renal failure. Hemodialysis was required in one patient in whom findings on renal nuclide scan were consistent with acute tubular necrosis. Pyuria was frequent, but proteinuria and more than five erythrocytes per high-power field were infrequent. Other features included initial hyponatremia and the combination of hypoproteinemia, hypoalbuminemia, hypocalcemia and hypophosphatemia of several days' duration. The hypoalbuminemia was believed to be due to exudation of protein from the intra- to the extravascular space. The hypoalbuminemia was believed to be due to exudation of protein from the intra- to the extravascular space. The hypocalcemia was probably related to the hypoalbuminemia. The pathogenesis of hypophosphatemia in the presence of acute renal failure is unclear. Following the intravenous administration of colloids, fluids and, in seven patients, dopamine, all recovered from the acute illness.

Adolescent↗

PubMed1981

Renal involvement in Refsum's disease.

Renal hemodynamic and tubular functions were measured in a patient with Refsum's disease before and after 12 weeks of twice-weekly plasmaphereses. Percutaneous renal biopsy was performed before initiation of plasmapheresis. These studies were performed to (1) define the nature of the renal lesions and the effects of phytanic acid accumulation on renal functions, and (2) assess the effects of lowering the plasma phytanic acid level on renal functions. The patient, a 39 year old woman, had lipiduria, glycosuria, cylindruria, minimal proteinuria and mild azotemia initially. Renal lesions consist of extensive vacuolization and mitochondrial changes of the tubular epithelial cells, vacuolization of the visceral epithelial cells of the glomeruli, and slight to moderate mesangial sclerosis. The impaired renal hemodynamic function and various tubular functions improved following plasmaphereses associated with reduction of plasma phytanic acid. Over-all clinical improvement was also evident.

Adult↗

PubMed1982

Glomerular and tubular function in non-oliguric acute renal failure.

Glomerular and tubular function were evaluated in 30 non-oliguric patients with increasing azotemia following open heart surgery. Fractional clearances (theta) of test solutes relative to that of inulin were determined. In 16 patients, theta dextran (radius 22 to 30 A) exceeded unity, a finding attributed to inulin backleak through necrotic tubules. These patients were classified as having acute renal failure; 14 subsequently required dialysis. In the remaining patients (N = 14), theta dextran was normal. These patients were considered to have prerenal failure; all recovered spontaneously. clearance of inulin (Cin) was lower in acute renal failure than in prerenal failure (12 +/- 2 versus 18 +/- 2 ml/min/1.73 m2; p less than 0.025). The apparent difference in glomerular filtration rate when Cin is used as an index was abolished, however, when Cin in acute renal failure was corrected for tubule backleak of inulin. In acute renal failure, fractional clearance of p-aminohippurate (theta PAH) was 7.1 +/- 1.0, and fractional excretion of potassium (FEk) was 160 +/- 18 percent. These findings strongly suggest that secretory ability in both proximal and terminal tubule augments, respectively, is preserved in acute renal failure. Compared with prerenal failure, the urine-to-plasma inulin ratio was lower (U/Pin = 10 +/- 1 versus 25 +/- 4; p less than 0.005) and FENa was higher (FENa = 5.1 +/- 1.5 versus 0.5 +/- 1.0 percent; p less than 0.01) in acute renal failure.

Acute Kidney Injury↗

PubMed1984

Interpreting the fractional excretion of sodium.

In most normal subjects, the fractional excretion of sodium is usually less than 1 percent but may be raised with an increase in salt intake. In acutely azotemic patients, a low fractional excretion of sodium usually indicates a prerenal process that is responsive to volume repletion. However, such a low fractional excretion of sodium also can be seen with azotemia due to hepatic or cardiac failure, as well as acute glomerulonephritis, pigment nephropathy, contrast nephrotoxicity, polyuric renal failure associated with burns, acute obstruction, renal transplant rejection, and occasionally non-oliguric acute renal failure, none of which is a volume-responsive process. A fractional excretion greater than 1 percent in acutely azotemic patients usually indicates intrinsic renal injury, but is consistent with volume depletion in patients receiving diuretics or in some patients with chronic renal insufficiency. Similarly, a low quotient in acute renal parenchymal injury is usually interpreted to indicate widespread tubular integrity, but is consistent with several different pathophysiologic processes. The fractional excretion of sodium must be interpreted in light of the specific clinical setting and other laboratory data to be useful in patient management.

Creatinine↗

PubMed1985

Comparison of effects of enalapril plus hydrochlorothiazide versus standard triple therapy on renal function in renovascular hypertension.

Renal function and antihypertensive drug efficacy were determined in a prospective, double-blind, multicenter study comparing enalapril plus hydrochlorothiazide with standard triple therapy (hydrochlorothiazide, timolol, and hydralazine) in 75 patients with documented renovascular hypertension. Both groups had significant mean decreases in systolic and diastolic blood pressures. Effective control of diastolic hypertension occurred in 96 percent of patients receiving enalapril compared with 82 percent of patients receiving the triple-drug regimen. Effective renal plasma flow was significantly increased by enalapril therapy. In contrast, the glomerular filtration rate had a bimodal response. In 80 percent of enalapril-treated patients, there was no significant change in the inulin clearance, although in 20 percent of patients (10), there was a 28 percent decrease in the inulin clearance with a concomitant 12 percent increase in renal plasma flow. Seven of the 10 patients had unilateral renal artery stenosis, but in all 10, it was high-grade stenosis (more than 80 to 90 percent stenosis). Although a significant rise in the serum creatinine level occurred in one patient in association with diuretic therapy, volume repletion reversed this azotemia. No oliguric acute renal failure occurred in the enalapril-treated group. The cause of the decrease in glomerular filtration rate induced by enalapril plus hydrochlorothiazide in a minority of patients with renal artery stenosis appears to be quite complex. Although the abolishment of the autoregulation of glomerular filtration secondary to blockage of angiotensin II appears to be a primary cause, the roles of decreased arterial pressure, renal counterbalance, concurrent diuretic therapy, and other hemodynamic factors that may maintain glomerular ultrafiltration pressure must also be considered. The results of this study show that enalapril plus hydrochlorothiazide is effective in treating renovascular hypertension. Special care is needed for a small group of patients with renovascular hypertension in whom there is a decrease in the glomerular filtration rate with this therapy. This may identify a subset of patients with unilateral or bilateral high-grade renal artery stenosis in whom alternative therapy--percutaneous angioplasty or surgical intervention--may be considered.

Adult↗

PubMed1985

The bleeding time as a preoperative screening test.

To examine the benefit of determination of the bleeding time as a preoperative screening test, the medical records of all patients who had a prolonged bleeding time during a six-month period were reviewed. At Northwestern Memorial Hospital, where the bleeding time test is part of the presurgical panel, 1,941 bleeding time determinations were performed during six months. Prolonged bleeding times were recorded in 110 preoperative patients, of whom 83 (75 percent) had bleeding risk factors, including drug ingestion, thrombocytopenia, and azotemia. In these patients, the bleeding time ranged unpredictably from 10 to more than 20 minutes. However, of the 27 patients without apparent risk factors, only two had bleeding times of more than 20 minutes. This small number probably does not justify the routine use of the test in all preoperative patients. Rather, the test should be used selectively for those subjects who, on the basis of history or laboratory evidence, are suspected of being at risk of hemorrhage. Moreover, even in these patients, prolongation of the bleeding time may not always be associated with excessive surgical blood loss.

Aspirin↗

PubMed1986

Transient and sustained recovery from renal shutdown in accelerated hypertension.

Ten black patients (eight men) with renal shutdown from accelerated hypertension were treated with hemodialysis. Renal function improved, and dialysis was discontinued after 6 +/- 2 months. Five patients (Group I) have maintained good renal function at 25 +/- 3 months of follow-up, whereas the other five (Group II) had deterioration again to advanced azotemia over 16 +/- 6 months. On admission, Group I patients had lower levels of serum creatinine (9 +/- 1.2 mg/dl [mean +/- SE] versus 13.6 +/- 1.7 mg/dl, p = 0.04) and urinary protein (0.98 +/- 0.78 g per day versus 2.17 +/- 1.5 g per day) and were more oliguric (451 +/- 145 ml per day versus 1,122 +/- 494 ml per day) than Group II. In Group I, renal shutdown was faster (8 +/- 4 days versus 38 +/- 28 days), recovery earlier (4 +/- 1.5 months versus 8 +/- 4 months) and greater (lowest serum creatinine level 1.9 +/- 0.3 mg/dl versus 5.7 +/- 1.7 mg/dl, p less than 0.05), and compliance better than in Group II. Two patients in the former group but none in the latter had peripheral schistocytes. It is concluded that the sustained recovery in Group I resulted from the resolution not only of the acute vascular lesions but also of tubular necrosis and microangiopathy, and the postrecovery deterioration in Group II is attributed to the more severe renal damage initially, the progression of the chronic vascular lesions in uncompliant patients, and possibly hyperfiltration damage in the remaining nephrons.

Acute Kidney Injury↗

PubMed1987

Unpredictability of clinical evaluation of renal function in cirrhosis. Prospective study.

The natural course of renal function in patients with cirrhosis and ascites but without azotemia is unclear. Therefore, a prospective evaluation of 23 non-azotemic cirrhotic patients with ascites was carried out over a three-year interval. Assessment included evaluation of serum electrolyte values, liver function tests, plasma renin levels, and parathyroid hormone levels. Renal function was determined by measurement of clearances of water and solute excretion, and simultaneous clearances of para-amino hippurate, inulin, and creatinine. The initial mean glomerular filtration rate was 66 ml/minute, serum creatinine level was 1.1 mg/dl, and blood urea nitrogen value was 13 mg/dl. The glomerular filtration rate showed marked variability among patients. On the basis of initial glomerular filtration rate, the patients were divided into three groups. Group I consisted of patients with supranormal filtration rates (mean 183 ml/minute), Group II constituted patients with normal filtration rates (mean 92 ml/minute), and Group III comprised patients with severely impaired filtration rates (mean 32 ml/minute). The serum creatinine level was below 1.5 mg/dl in all three groups. Serial measurement of renal function was performed in 18 patients over a mean of 310 days (range four to 1,176 days). Eighty-six percent of patients studied from Groups I and II maintained a normal or supranormal glomerular filtration rate over one year. However, most patients in Group III showed a progressive decline in filtration rate, despite no change in serum creatinine value. Sixty-seven percent of Group III patients died over a mean of one year. The mean 24-hour solute excretion among Group III patients was only 263 mOsm per day, significantly less than the control value of 874 mOsm per day in other hospitalized non-cirrhotic patients. The serum creatinine level frequently failed to rise above normal even when the glomerular filtration rate was very low (less than 25 ml/minute), and creatinine clearance overestimated inulin clearance by a factor of two in Group III patients. However, the creatinine index was an aid in determining true glomerular filtration rate and may be a useful clinical test in the evaluation of renal insufficiency in cirrhotic patients with normal serum creatinine values. Many patients with cirrhosis and ascites will have a glomerular filtration rate of less than 60 ml/minute but a normal serum creatinine level. These patients may constitute a previously unrecognized large group.

Adult↗

PubMed1987

Renal, volume, and hormonal changes during therapeutic administration of recombinant interleukin-2 in man.

Changes in blood pressure, renal function, and fluid balance were studied in 12 patients receiving intravenous recombinant interleukin-2 (IL-2) (100,000 units/kg every eight hours) over five days for treatment of metastatic melanoma and renal and colorectal cancers. The IL-2 regimen produced progressive hypotension, azotemia, and sodium avidity (fractional excretion of sodium = 0.20 +/- 0.07 percent) despite massive fluid administration (mean: 18.4 liter per five days) and weight gain (mean: 4.0 kg). Plasma renin activity rose. Hypoalbuminemia developed rapidly (3.6 +/- 0.1 g/dl to 2.2 +/- 0.1 g/dl, p less than 0.01) with widespread edema formation despite normal central venous pressures. Hematocrit did not change during the IL-2 period, consistent with a "capillary-leak." Hemodynamic and renal functional changes reversed after the IL-2 regimen was discontinued, but hypoalbuminemia and elevated urinary n-acetyl-glucosaminidase levels persisted after six days. These studies demonstrate widespread hemodynamic and vascular effects of IL-2 administration that limit its safe use and suggest a possible role for the lymphokine in mediating cardiovascular instability under other circumstances, such as endotoxic shock.

Adult↗

PubMed1988

De novo focal glomerulosclerosis after kidney transplantation.

A transplanted kidney in a patient developed focal and segmental glomerulosclerosis, associated with severe systemic hypertension, proteinuria, progressive azotemia, and allograft hypertrophy. A pediatric kidney with two main arteries was used, and occlusion of the artery supplying the upper pole resulted in infarction of this portion of the allograft. Because other known factors predisposing to focal sclerosis were absent, it is postulated that renal hemodynamic changes associated with reduction in functioning renal mass, attended by striking stimuli for renal hypertrophy, resulted in progressive damage. The implications of these concepts are discussed in relation to the progression of renal diseases.

Adult↗

PubMed1992

Evolution of the treatment of hypertension: what really matters in the 1990s?

Over the past decade we have seen a shift in the strategy for the treatment of hypertension, from stepped therapy--involving a highly structured, unvarying series of steps--to recommendations for more individualized treatment. How shall we accomplish that goal? Severe hypertension provides a clear indication to bypass earlier recommendations. Demographic data such as age, gender, and race, often cited, have proved less helpful. Concomitant medical problems, which are found in greater than 50% of hypertensive patients, are most often the crucial determinants in the selection of antihypertensive therapy. Concurrent coronary artery disease, diabetes mellitus, heart failure, azotemia, asthma, chronic obstructive pulmonary disease, borderline cognitive dysfunction, anxiety, and depression are all common. Each has implications for antihypertensive therapy. Moreover, blood pressure reduction is a surrogate for our real goal, which is reduction of cardiovascular risk. Thus, consideration of concomitant medical problems has extended to left ventricular hypertrophy, obesity, hyperlipidemia, and insulin resistance as additional risk factors in hypertension. Consideration of all of these factors makes it possible to individualize antihypertensive therapy in most patients.

Age Factors↗

PubMed1993

Acute tumor lysis syndrome in patients with high-grade non-Hodgkin's lymphoma.

PURPOSE: To identify patients with lymphoma at risk for tumor lysis after chemotherapy. PATIENTS AND METHODS: The case records of 102 patients receiving combination chemotherapy for non-Hodgkin's lymphoma (intermediate to high-grade histology) were reviewed. Patients were considered to have "laboratory tumor lysis" if two of the following metabolic changes occurred within 4 days of treatment: a 25% increase in the serum phosphate, potassium, uric acid, or urea nitrogen concentrations, or a 25% decline in the serum calcium concentration. "Clinical tumor lysis" was defined as laboratory tumor lysis plus one of the following: a serum potassium level greater than 6 mmol/L, a creatinine level greater than 221 mumol/L, or a calcium level less than 1.5 mmol/L, the development of a life-threatening arrhythmia, or sudden death. RESULTS: Laboratory tumor lysis occurred in 42% of patients and clinical tumor lysis in 6%. There was no statistical difference in the frequency of either tumor lysis syndrome among lymphoma subgroups. Clinical tumor lysis occurred more frequently in patients with pretreatment renal insufficiency (serum creatinine level greater than 132 mumol/L) than in patients with normal renal function (36% versus 2%; p = 0.01). The development of azotemia correlated with high pretreatment serum lactate dehydrogenase concentrations (p < 0.01; r2 = 0.11). CONCLUSION: Clinically significant tumor lysis is a rare occurrence in patients with lymphoma when they are receiving allopurinol. However, tumor lysis can occur in patients with all types of moderate to high-grade non-Hodgkin's lymphoma. Patients with a high serum lactate dehydrogenase level or renal insufficiency are at increased risk for metabolic complications after chemotherapy and should be closely monitored.

Acute Disease↗