Calcium Oxalate Stone Agglomeration Inhibition [tm] Reflects Renal Stone-Forming Activity.

Louisiana and other Gulf South states comprise a "Stone Belt" where calcium oxalate stone formers (CaOx SFs) are found at a high rate of approximately 5%. In these patients, the agglomeration of small stone crystals, which are visible in nearly all morning urine collections, forms stones that can become trapped in the renal parenchyma and the renal pelvis. Without therapy, about half of CaOx SFs repeatedly form kidney stones, which can cause excruciating pain that can be relieved by passage, fragmentation (lithotripsy), or surgical removal. The absence of stones in "normal" patients suggests that there are stone inhibitors in "normal" urines.At the Ochsner Renal Stone Clinic, 24-hour urine samples are collected by the patient and sent to the Ochsner Renal Stone Research Program where calcium oxalate stone agglomeration inhibition [tm] measurements are performed. Urine from healthy subjects and inactive stone formers has demonstrated strongly inhibited stone growth [tm] in contrast to urine from recurrent CaOx SFs. [tm] data from 1500 visits of 700 kidney stone patients have been used to evaluate the risk of recurrence in Ochsner's CaOx SF patients. These data have also been used to demonstrate the interactive roles of certain identified urinary stone-growth inhibitors, citrate and Tamm-Horsfall protein (THP), which can be manipulated with medication to diminish recurrent stone formation. Our goal is to offer patients both financial and pain relief by reducing their stones with optimized medication, using medical management to avoid costly treatments.

Agglomeration inhibition reflected stone-forming activity during long-term potassium citrate therapy in calcium stone formers.

OBJECTIVES: The agglomeration of preformed crystals of calcium oxalate has been hypothesized to be the rate-limiting step in renal stone-forming activity (SFA). The effect of urine on the in vitro inhibition of agglomeration of seed crystals of calcium oxalate monohydrate, designated [tm], has been used to monitor SFA in calcium oxalate stone formers (CaOxSF). The objective of the present study was to determine whether [tm] could be used to help monitor the long-term effectiveness of oral potassium citrate therapy (K-Cit-Rx) in CaOxSF. METHODS: Clinic and radiographic (or ultrasound) reports were evaluated for 80 patients, aged 20 to 72 years, 55 men and 25 women, who were treated with oral K-Cit for recurrent calcium oxalate urolithiasis at the Ochsner Stone Clinic between January 1992 and July 1996. Seventy-five of these patients had at least one 24-hour citrate excretion rate of less than 3.0 mm/day before or after K-Cit-Rx. SFA graded on a scale of -2 to +2 by radiographic criteria was combined with information on stone passage to evaluate clinical stone status, and 24-hour urine collections were evaluated for volume, pH, calcium, citrate, uric acid, oxalate, creatinine, and [tm] on free diet before and after 6 to 53 months of K-Cit-Rx. Historical information on procedures performed for urolithiasis before and on K-Cit-Rx was also reviewed. RESULTS: K-Cit-Rx resulted in increased urine pH (P <0.0001) and decreased calcium (P=0.0475), [tm] (P=0.0045), number of stones passed per year (P=0.0016), and remedial procedures per year (P <0.0001). Patients taking allopurinol in addition to K-Cit required higher doses (P <0.0001) of K-Cit to control their disease, had lower pretreatment urine pH (P=0.0493), and showed greater increase in urine citrate (P=0.0092) than those on K-Cit alone. Those taking high-dose K-Cit were younger (P=0.0363) and showed greater decrease in SFA (P=0.0005) than those taking lower doses. A small group of 10 medication refractory patients, who retained (n=9) or increased (n=1) their stone burden during K-Cit-Rx, was identified. Compared with the medication-responsive group, the refractory patients were older (P=0.0124), and had greatly increased SFA (P <0.0001) and higher (P=0.0347) urine pH before and during (P=0.0173) treatment (data not shown). CONCLUSIONS: The data confirm that [tm] can be used not only to verify previously documented stone formation rate but also to help evaluate the long-term effectiveness of therapy. In this report, changes in [tm] after K-Cit-Rx reflected decreased stone formation rate and decreased remedial procedures.

Urinary Tamm-Horsfall protein increased after potassium citrate therapy in calcium stone formers.

OBJECTIVES: To evaluate the effect of oral potassium citrate therapy on urinary excretion rates of citrate. Tamm-Horsfall protein (THP), and on calcium oxalate monohydrate crystal agglomeration inhibition [tm], in patients with recurrent calcium stone formation. METHODS: To evaluate the effect of oral therapy with potassium citrate on urinary citrate, THP, and [tm], 24-hour urine samples were collected before and at least 2 months after initiation of oral potassium citrate therapy in 33 calcium stone-forming patients who had no dietary restrictions. The citrate concentration was measured by an adaptation of a citrate lyase method. Urinary disaggregated THP concentration was determined with a quantitative enzyme-linked immunosorbent assay. The [tm] was determined by observing the effects of patients' urine, before and after oral potassium citrate therapy, on the uptake of 45Ca2+ onto the surfaces of added preformed calcium oxalate crystals in a supersaturated solution of calcium oxalate, using the in vitro kinetic method described by other investigators. RESULTS: We observed an increased urinary excretion rate of citrate from a mean of 1.9 mmol/24 h prealkali to 2.6 mmol/24 h postalkali (P < 0.0004) and of THP from a mean of 94.0 mg/24 h prealkali to 199.3 mg/24 h postalkali (P < 0.0016). A corresponding increase in [tm] from a mean of 177.1 minutes prealkali to 221.0 minutes postalkali (P < 0.024) was also observed. CONCLUSIONS: To our knowledge this is the first report correlating increased urinary citrate with THP excretion rate following oral alkalinization with potassium citrate in calcium stone formers. Of clinical importance is the corresponding increase in [tm], which was previously shown to be inversely related to stone-forming activity. Moreover, urinary citrate and THP are known to have a synergistic effect on [tm]. Our data suggest that the effectiveness of potassium citrate therapy in calcium stone-forming patients may, at least in part, be due to increased levels of THP.

Calcium oxalate stone agglomeration reflects stone-forming activity: citrate inhibition depends on macromolecules larger than 30 kilodalton.

To evaluate the clinical utility of in vitro calcium oxalate monohydrate (COM) crystallization kinetics measurements and to determine the effect of quantitative removal of urinary Tamm-Horsfall glycoprotein on such measurements, we examined 24-hour, room temperature urine collections of patients from our Stone Clinic and of normal subjects from our research laboratories at Ochsner Medical Institutions in New Orleans, LA, and compared their COM kinetic parameters in vitro before and after urine ultrafiltration (30 kd). Data from 53 calcium oxalate stone-forming patients (26% women; mean age, 47 years) who demonstrated radiographic or other evidence of forming at least one stone were compared with data from 22 healthy volunteers (25% women; mean age, 40 years). Hypercalciuria (> 7.5 mm/24 hr), hyperoxaluria (> 0.5 mm/24 hr), and hypocitraturia (< 2.0 mm/24 hr) were present in 38%, 26%, and 26% of the patient population, respectively. Urinary creatinine, urate, calcium, citrate, phosphate, oxalate, pH, volume, total immunoreactive-disaggregated Tamm-Horsfall glycoprotein, and the urine's effects on COM solubility, percent crystal growth inhibition, and crystal agglomeration inhibition [tm] were determined. Calcium oxalate monohydrate agglomeration inhibition, [tm], was reduced in stone-forming patients. It decreased with increasing stone frequency, making [tm] a useful tool for measuring the risk of stone recurrence. Urinary Tamm-Horsfall glycoprotein and citrate concentrations were linearly related to COM agglomeration inhibition. Their effects were synergistic. Tamm-Horsfall glycoprotein removal from urine reduced COM agglomeration inhibition dramatically. Alkali therapy increased urinary citrate concentration and increased [tm].(ABSTRACT TRUNCATED AT 250 WORDS)

Complications of flow-directed balloon-tipped catheters.

Acute or short-term complications following the use of flow-directed balloon-tipped catheters are well recognized. Long-term sequelae are rarely reported. We report herein an early complication of pulmonary arterial rupture with infarction followed by the delayed development of a pulmonary arterial aneurysm.

Immediate hemodynamic response to furosemide in patients undergoing chronic hemodialysis.

To evaluate the effect of furosemide on cardiovascular hemodynamics in patients with end-stage renal failure, we studied ten patients undergoing hemodialysis three times a week. Arterial pressure, heart rate, and cardiac output (indocyanine green dye) were measured in triplicate; total peripheral resistance and central blood volume were calculated by standard formulas. Hemodynamics were determined at baseline and 5, 10, 15, and 30 minutes after intravenous (IV) bolus injection of furosemide 60 mg. Furosemide produced a decrease in central blood volume of -13% +/- 2.2% from pretreatment values (P less than .01) that was most pronounced five minutes after injection, together with a fall in cardiac output (from 6.76 +/- 0.59 to 6.17 +/- 0.52 L/min, P less than .10). Stroke volume decreased with a maximum fall occurring after 15 minutes (from 84 +/- 7 to 79 +/- 7 mL/min, P less than .05), and total peripheral resistance increased (from 15.8 +/- 2.1 to 17.8 +/- 2.3 units, P less than .05) after furosemide. Arterial pressure and heart rate did not change. The decrease in central blood volume reflects a shift of the total blood volume from the cardiopulmonary circulation to the periphery, suggesting dilation of the peripheral venous bed. Thus, even in patients undergoing hemodialysis, furosemide acutely decreases left ventricular preload by venous dilation and should therefore prove to be beneficial in acute volume overload.

Long-term therapy for heart failure with continuous ambulatory peritoneal dialysis.

This article reports the treatment with continuous ambulatory peritoneal dialysis of a patient with intractable congestive heart failure secondary to an ischemic cardiomyopathy. Although the use of peritoneal dialysis to treat refractory heart failure is not new, the advent of an effective continuous peritoneal dialysis system has allowed its use over prolonged periods of time. The two-year treatment interval described herein represents the longest reported application of this technique, to the best of our knowledge.

Carcinoembryonic antigen: assay following heat compared with perchloric acid extraction in patients with colon cancer, non-neoplastic gastrointestinal diseases, or chronic renal failure.

Heat inactivation has been proposed as an alternative to perchloric acid (PCA) precipitation for the extraction of carcinoembryonic antigen (CEA) from human plasma. We examined a commercial RIA kit using heat inactivation, and compared results with those obtained with PCA precipitation. Adequate sensitivity (1.5 micrograms CEA/l plasma), satisfactory analytical recovery of CEA added to plasma, and dilutional linearity of samples found to have elevated CEA concentrations, were demonstrated for the heat-inactivation assay. Between-assay precision was better with the heat inactivation than with the PCA assay. Although the absolute concentration of CEA estimated after heat inactivation was consistently lower than that estimated after PCA extraction of plasma specimens, there was excellent correlation between results obtained with the two methods in colon cancer patients free of disease, colon cancer patients with residual or recurrent disease, patients with benign gastrointestinal disease, and in patients with chronic renal failure. We conclude that the heat-inactivation assay is an excellent alternative to the PCA assay.

Antiadrenergic therapy: special aspects in hypertension in the elderly.

The effect of antiadrenergic treatment with methyldopa was studied in 17 patients with established essential hypertension who were subdivided with respect to age in a group younger (n = 10; mean age, 47 +/- 2.4 (SEM) years; and a group older than 60 years of age (n = 7, mean age, 67 +/- 2.8 SEM). The fall in arterial pressure was associated with a significant (p less than 0.05) decrease in cardiac output and heart rate in patients over 60 years of age and no change in total peripheral resistance, whereas a (nonsignificant) fall in resistance occurred in younger patients. In both age groups, a significant (p less than 0.05 and less than 0.01, respectively) decrease in plasma norepinephrine levels was observed, whereas epinephrine and dopamine showed no changes. Pre- and posttreatment values of mean arterial pressure correlated directly with plasma norepinephrine values (r = 0.35 p less than 0.05). Regardless of whether cardiac output was reduced or remained unchanged, renal blood flow, plasma and total blood volume did not change in either group with antiadrenergic treatment. Further, reflexive cardiac changes (responses to isometric exercise and upright tilt) remained qualitatively unchanged. It is concluded that antiadrenergic treatment with methyldopa lowers arterial pressure additionally by decreasing circulating norepinephrine levels. The antihypertensive effect is associated with a fall in peripheral resistance in the younger and a decrease in cardiac output in the older patients, and does not compromise renal blood flow or cardiac reflexive responses.

Adverse effects of antihypertensive drugs.

Early essential hypertension is asymptomatic and should remain so throughout treatment. In view of the increasing number of available antihypertensive agents, clinicians need to become familiar with the potential side effects of these drugs. By placing more emphasis on non-pharmacological treatment (sodium restriction, weight loss, exercise) and thoroughly evaluating each case in particular, the pharmacological regimen can be optimally tailored to the patient's needs. Potential side effects should be predicted and can often be avoided; if they become clinically significant they should be rapidly recognised and corrected. These side effects can be easily remembered in most instances, as they fall into 3 broad categories: (a) those caused by an exaggerated therapeutic effect; (b) those due to a non-therapeutic pharmacological effect; and (c) those caused by a non-therapeutic, non-pharmacological effect probably representing idiosyncratic reactions. This review focuses mainly on adverse effects of the second and third kind. Each group of drugs in general shares the common side effects of the first two categories, while each individual drug has its own idiosyncratic side effects.

Renal papillary necrosis and pyelonephritis accompanying fenoprofen therapy.

Renal papillary necrosis occurred after fenoprofen calcium administration in a patient with systemic lupus erythematosus and urinary tract infection. Possible mechanisms of renal damage may be hypersensitivity, decreased blood flow, and decreased production of a prostaglandin E-like substance.

Gold nephropathy in juvenile rheumatoid arthritis.

A 2-year-old girl was treated with gold salts for juvenile rheumatoid arthritis. Treatment had to be discontinued when persistent proteinuria was detected. As this case report indicates, close monitoring of the urine is mandatory during treatment with gold salts to detect early signs of toxicity: hematuria followed by casts and then proteinuria as therapy is continued. Histologic examination with electron microscopy will help to differentiate the different forms of gold toxicity. When the findings are consistent with gold-induced renal involvement, therapy should be discontinued. The gold nephropathy usually resolves in time, with no permanent renal damage.

Hypertension after clonidine withdrawal.

Rebound hypertension occurred in two patients upon clonidine withdrawal. Treatment of the hypertensive crisis consists of both alpha- and beta-adrenergic receptor blockade, reserpine, or the reintroduction of clonidine. With effective control of pressure during the crisis, long-term antihypertensive therapy must be resumed.