The hemodynamic effects of intravenous digoxin-binding fab immunoglobulin in severe preeclampsia: a double-blind, randomized, clinical trial.

OBJECTIVE: An endogenous digitalis-like factor (EDLF) has been implicated in the pathophysiology of preeclampsia (PE). This hypothesis is supported by two cases of preeclampsia in which administration of digoxin immune Fab (DIF) reduced mean arterial pressure (MAP). STUDY DESIGN: To study this observation further, we performed a double-blind, placebo-controlled, randomized clinical trial to examine the effects on MAP of intravenous DIF given after delivery in 26 subjects with severe preeclampsia. Treating obstetricians were blinded to subject assignment and were allowed to use standard antihypertensive drugs during the trial. RESULTS: The primary outcome, a significant difference in blood pressure between the two groups over the 24-h period of observation after the intervention, was not supported. However, mean MAP was significantly lower in the DIF-treated subjects for the first 4 h after therapy as compared with controls (P=0.05). Six subjects (46.2%) in the placebo arm were given conventional antihypertensive medications by their obstetrician for blood pressure >160 mm Hg systolic or >110 mm Hg diastolic, compared with zero subjects in the treatment arm (P=0.01). A trend towards increased creatinine clearance was observed in DIF-treated subjects (137.6+/-42.6 versus 104.1+/-43.4, P=0.07). CONCLUSION: These results support the hypothesis that EDLF contributes to the elevated blood pressure in preeclampsia and suggests a possible role for DIF as a treatment for this condition.

Repeated dosing of digoxin-fragmented antibody in preterm eclampsia.

Early onset eclampsia has significant morbidity and mortality for both the mother and fetus. No effective treatment exists at present except delivery and seizure prophylaxis with magnesium sulfate. We report the novel use of a fragmented ovine antibody against digoxin for the treatment of eclampsia. A 16-year-old primagravida at 29 weeks 5/7 days gestation presented with clinical diagnosis of eclampsia and was treated with compassionate off-label use of digoxin-fragmented ovine antibody (Digibind Glaxo Smith Kline, Research Triangle Park, NC, USA). Improvement of her underlying disorder during a 48 h treatment window was noted without adverse maternal or neonatal outcome. We suggest digoxin-fragmented ovine antibody as a possible intervention in preterm pregnancies complicated by pre-eclampsia or eclampsia.

Candidate gene analysis in African Americans with renal failure.

A search for renal failure genes is being conducted in African American sib pairs concordant for end-stage renal disease (ESRD) recruited predominantly from the dialysis population in the Southeastern United States. Family history data is being collected in patients from more than 250 individual dialysis units. Patients with polycystic kidney disease, Alport's Syndrome and confirmed urologic disease are excluded. The study employs a candidate gene strategy initially, followed by a genome-wide search for linkage between polymorphic markers and the phenotype "ESRD."

Summary of a symposium on natriuretic and digitalis-like factors.

An international symposium on natriuretic and digitalis-like factors was convened for the first time since 1992. Topics discussed included structures and biosynthesis of endogenous digitalis-like factors (EDLF), biologic activities, physiology function and role of EDLF in hypertension, and novel natriuretic factors. Progress was reported in determining the exact structure of an isomer of ouabain isolated from bovine hypothalamus. Evidence was presented supporting the existence of a second mammalian EDLF that resembles steroids found in toads (bufodienolides). Support for endogenous synthesis of mammalian EDLF was also presented. Mammalian EDLF were reported to have effects which are different from those possessed by digitalis like steroids derived from plants. New evidence was presented implicating EDLF in various forms of hypertension in humans and animal models. Finally, several unique natriuretic factors that do not inhibit Na, K ATPase and that appear to play a role in mammalian volume regulation were discussed.

CLCN5 mutation Ser244Leu is associated with X-linked renal failure without X-linked recessive hypophosphatemic rickets.

This study demonstrates that a missense mutation in the voltage gated chloride channel, CLCN5, can cause X-linked renal failure without X-linked recessive hypophosphatemic rickets. A large kindred (Family A), initially evaluated in 1974 with an inherited syndrome characterized by hypercalciuria, nephrocalcinosis, low molecular weight proteinuria, renal tubular acidosis, and renal failure, was clinically re-evaluated and genetically characterized. Medical histories, physical examinations, blood chemistries, and 24-hour urine collections were obtained from 48 family members. Both female and male family members exhibited hypercalciuria, nephrolithiasis, and low molecular weight proteinuria. However, only men developed renal insufficiency, consistent with an X-linked recessive gene defect. Genetic linkage located the disease locus on the proximal short arm of the X chromosome (Xp11) where a voltage gated chloride channel gene, CLCN5, had previously been mapped. DNA sequence of the CLCN5 gene demonstrated a missense mutation (Ser244Leu) in affected family members. The same missense mutation has previously been shown to cause X-linked recessive hypophosphatemic rickets. No affected member of Family A had evidence of chronic hypophosphatemia, clinically significant rickets, or osteomalacia. We hypothesize that genetic background, environment, diet, or an unidentified modifying gene may account for the differing phenotypes resulting from this shared gene defect.

Role of nitric oxide in the evolution of renal ischemia in two-kidney, one-clip renovascular hypertension.

To clarify the role of nitric oxide (NO) in the pathogenesis of renovascular hypertension, we examined the effects of long-term oral administration of either the precursor substrate L-arginine or the NO synthesis inhibitor Nomega-nitro-L-arginine (L-NA) on systemic and renal hemodynamics in dogs with chronic two-kidney, one-clip (2K-1C) renovascular hypertension. Furthermore, the importance of NO in maintaining kidney function in chronic renal ischemia was evaluated. Chronic inhibition of NO production aggravated the rise in blood pressure (L-NA 117.7+/-6.8 vs. control 107.2 3.3 mmHg, p < 0.05 on day 1) and stimulated marked bradycardia (L-NA 84.9+/-3.2 vs. control 94.6+/-2.6 beats/min, p < 0.05 on day 1). These changes were associated with significant reductions in renal plasma flow (RPF, L-NA 0.03+/-0.02 vs. control 0.85+/-0.20 ml/min/kg, p < 0.01) and glomerular filtration rate (GFR, L-NA 0.02+/-0.01 vs. 0.22+/-0.05 ml/min/kg, p < 0.01) in the ischemic kidney. In contrast, in the contralateral non-clipped kidney, chronic inhibition of NO production induced a significant reduction in RPF with no significant change in GFR. Oral administration of L-arginine had no effect on the magnitude of hypertension. L-arginine significantly improved RPF (2.76+/-0.49 ml/min/kg) and GFR (0.61+/-0.08 ml/min/kg) in the ischemic kidney, whereas the elevation of RPF and GFR in the non-clipped kidney was not significant. Unilateral renal artery occlusion in these hypertensive dogs resulted in diffuse atrophic tubulointerstitial changes in the ischemic kidney. These changes were markedly aggravated by NO synthesis inhibition. On the other hand, L-arginine treatment significantly protected against the morphological changes of renal ischemia. These data show that NO plays a key role in the maintenance of renal function during the evolution of hypertension induced by chronic renal ischemia. In addition, these data demonstrate that renovascular hypertension is associated with a compensatory increase in the vasodilator function of the vascular endothelium.

Ischemic nephropathy: an important cause of renal disease in the elderly.

RAOD is an important cause of progressive renal failure in the elderly population. We can expect to see an increasing incidence of this disease as the population ages. A non-invasive test for detecting this condition with a high degree of sensitivity and specificity has been developed, although the technique is sufficiently difficult that it is currently available in only a few specialized centers. Indications for intervention to preserve renal function are not clear. Application of stenting to renal artery lesions has lead some to advocate treatment of these lesions empirically when they are detected much as is done with coronary artery lesions in patients with ischemic heart disease. Given the present state of knowledge, this is not an unreasonable approach. However, not all lesions progress and their role in causing renal failure is not clear in all cases. Furthermore, intervention can cause worsening of renal failure in some cases and actually precipitate the need for dialysis. Several recommendations are reasonable based on this review. Patients over 50 starting dialysis with renal failure of unknown etiology should be screened for RAOD. Those with bilateral lesions should be offered an intervention. Patients with mild or moderate renal failure of unknown etiology over age 50 should also be screened. Those with bilateral lesions should be offered an intervention with conservative management for those with unilateral lesions. The later group should be monitored on a yearly basis for the development of contralateral lesions or significant bilateral renal atrophy. If either of these eventualities develop, intervention should be offered. These recommendations would have to be considered in the light of the possible need to perform an intervention for the treatment of hypertension.

Achievement and safety of a low blood pressure goal in chronic renal disease. The Modification of Diet in Renal Disease Study Group.

The Modification of Diet in Renal Disease Study showed a beneficial effect of a lower-than-usual blood pressure (BP) goal on the progression of renal disease in patients with proteinuria. The purpose of the present analyses was to examine the achieved BP, baseline characteristics that helped or hindered achievement of the BP goals, and safety of the BP interventions. Five hundred eighty-five patients with baseline glomerular filtration rate between 13 and 55 mL/min per 1.73 m2 (0.22 to 0.92 mL/s per 1.73 m2) were randomly assigned to either a usual or low BP goal (mean arterial pressure < or = 107 or < or = 92 mm Hg, respectively). Few patients had a history of cardiovascular disease. All antihypertensive agents were permitted, but angiotensin-converting enzyme inhibitors (with or without diuretics) followed by calcium channel blockers were preferred. The mean (+/- SD) of the mean arterial pressures during follow-up in the low and usual BP groups was 93.0 +/- 7.3 and 97.7 +/- 7.7 mm Hg, respectively. Follow-up BP was significantly higher in subgroups of patients with preexisting hypertension, baseline mean arterial pressure > 92 mm Hg, a diagnosis of polycystic kidney disease or glomerular diseases, baseline urinary protein excretion > 1 g/d, age > or = 61 years, and black race. The frequency of medication changes and incidence of symptoms of low BP were greater in the low BP group, but there were no significant differences between BP groups in stop points, hospitalizations, or death. When data from both groups were combined, each 1-mm Hg increase in follow-up systolic BP was associated with a 1.35-times greater risk of hospitalization for cardiovascular or cerebrovascular disease. Lower BP than usually recommended for the prevention of cardiovascular disease is achievable by several medication regimens without serious adverse effects in patients with chronic renal disease without cardiovascular disease. For patients with urinary protein excretion > 1 g/d, target BP should be a mean arterial pressure of < or = 92 mm Hg, equivalent to 125/75 mm Hg.

Prevalence of hypertension in 1,795 subjects with chronic renal disease: the modification of diet in renal disease study baseline cohort. Modification of Diet in Renal Disease Study Group.

The Modification of Diet in Renal Disease Study was a multicenter trial of the effect of protein restriction and strict blood pressure control on the progression rate of chronic renal failure of multiple causes. At the first baseline visit, 1,795 screened patients with renal disease had blood pressure measured, antihypertensive medications recorded, glomerular filtration rate (GFR) determined by 125I-iothalamate clearance, a nutritional assessment, and a 24-hour urine collection to determine sodium and potassium levels. A total of 1,494 patients in this cohort were classified as hypertensive (83%) and the remainder (301 patients) as nonhypertensive. Ninety-one percent of the hypertensive subjects were on treatment, 54% being controlled to a blood pressure of < or = 140/90 mm Hg. To better understand the factors that contribute to the development of hypertension in chronic renal disease, some determinants of the prevalence of hypertension in this cohort were investigated. Compared with normotensive subjects, hypertensive patients were older (51.2 +/- 12.7 years v 46.6 +/- 13.1 years [mean +/- SD]), had a higher body mass index (BMI; 27.5 +/- 4.7 kg/m2 v 25.4 +/- 4.2 kg/m2), and had a lower GFR (37.8 +/- 19.6 mL/min/1.73 m2 v 50.1 +/- 25 mL/min/1.73 m2). All these differences were significant (P < 0.01). The prevalence of hypertension was significantly higher for men than for women (86% v 80%; P = 0.001), and for blacks than for whites (93% v 81%; P < 0.001). The prevalence of hypertension was higher in subjects with glomerular disease than in those with tubulointerstitial disease (85% v 62.6%; P < 0.001). The prevalence of hypertension varied inversely with GFR (from 66% at a GFR of 83 mL/min/1.73 m2 to 95% at a GFR of 12 mL/min/1.73 m2). The prevalence of hypertension varied directly with BMI (from 70% with a BMI at the 10th percentile to 94% with a BMI at the 97th percentile). This relationship was independent of GFR. Multiple logistic regression analysis showed five predictors in decreasing order of significance as determined by chi-square values: GFR, 83.2; BMI, 36.7; black race, 19.9; increasing age, 14.5 (all P < 0.001); and male gender, 5.1 (P = 0.024). Salt intake was not a determinant of blood pressure status. These results confirm previous reports indicating that hypertension in renal disease is determined by the level of renal function. For the first time, three factors known to predict blood pressure levels in populations with normal renal function were also shown to be determinants of blood pressure in renal disease: BMI, black race, and age. In addition, the data suggest that hypertension is inadequately treated in more than half of patients with chronic renal disease in the United States.

Final outcome results of the Multicenter Isradipine Diuretic Atherosclerosis Study (MIDAS). A randomized controlled trial.

OBJECTIVE: To compare the rate of progression of mean maximum intimal-medial thickness (IMT) in carotid arteries, using quantitative B-mode ultrasound imaging, during antihypertensive therapy with isradipine vs hydrochlorothiazide. DESIGN: Randomized, double-blind, positive-controlled trial. SETTING: Nine medical center clinics. POPULATION: A total of 883 patients with baseline mean +/- SD systolic and diastolic blood pressure (SBP and DBP, respectively) of 149.7 +/- 16.6 and 96.5 +/- 5.1 mm Hg, age of 58.5 +/- 8.5 years, and maximum IMT of 1.17 +/- 0.20 mm. INTERVENTIONS: Twice daily doses of isradipine (2.5-5.0 mg) or hydrochlorothiazide (12.5-25 mg). MAIN OUTCOME MEASURE (PRIMARY END POINT): Rate of progression of mean maximum IMT in 12 carotid focal points over 3 years. RESULTS: There was no difference in the rate of progression of mean maximum IMT between isradipine and hydrochlorothiazide over 3 years (P=.68). There was a higher incidence of major vascular events (eg, myocardial infarction, stroke, congestive heart failure, angina, and sudden death) in isradipine (n=25; 5.65%) vs hydrochlorothiazide (n=14; 3.17%) (P=.07), and a significant increase in nonmajor vascular events and procedures (eg, transient ischemic attack, dysrhythmia, aortic valve replacement, and femoral popliteal bypass graft) in isradipine (n=40; 9.05%) vs hydrochlorothiazide (n=23; 5.22%) (P=.02). At 6 months, mean DBP decreased by 13.0 mm Hg in both groups, and mean SBP decreased by 19.5 mm Hg in hydrochlorothiazide and 16.0 mm Hg in isradipine (P=.002); the difference in SBP between the 2 groups persisted throughout the study but did not explain the increased incidence of vascular events in patients treated with isradipine. CONCLUSION: The rate of progression of mean maximum IMT in carotid arteries, the surrogate end point in this study, did not differ between the 2 treatment groups. The increased incidence of vascular events in patients receiving isradipine compared with hydrochlorothiazide is of concern and should be studied further.

Capillary electrophoresis for the determination of glomerular filtration rate using nonradioactive iohexol.

High-performance liquid chromatography (HPLC) has been used as an alternative to the isotopic method to calculate glomerular filtration rate (GFR). With the HPLC method, serum iohexol or iothalamate levels are measured, and the plasma clearance rate of the compound is used as a surrogate for GFR. However, HPLC is a labor-intensive procedure, which limits its usefulness in the clinical setting. Capillary electrophoresis, a newer technique in which electrophoretic separations are performed in capillary tubes, is easier and faster than HPLC. We used capillary electrophoresis for the determination of serum iohexol levels and the calculation of GFR. Patients underwent a simultaneous 125I-iothalamate clearance test and a plasma iohexol clearance test to determine GFR. Mean GFR (+/-SD) was 70.9 +/- 29.9 mL/min (range, 14.5 to 131 mL/min) in 52 patients as determined by standard iothalamate clearance methods. For iohexol clearance, the correlation coefficient and standard error were 0.93 and 10.9 mL/min, respectively, using capillary electrophoresis compared with the iothalamate method. Capillary electrophoresis is a simple, rapid method that can be used to calculate GFR and provides results at least as accurate as those obtained by HPLC and x-ray fluorescence.

Habitual use of acetaminophen as a risk factor for chronic renal failure: a comparison with phenacetin.

Six epidemiologic studies in the United States and Europe indicate that habitual use of phenacetin is associated with the development of chronic renal failure and end-stage renal disease (ESRD), with a relative risk in the range of 4 to 19. As a result of these and other studies, phenacetin has now been withdrawn from the market in most countries. However, three case control studies, one each in North Carolina, northern Maryland, and West Berlin, Germany, showed that habitual use of acetaminophen is also associated with chronic renal failure and ESRD, with a relative risk in the range of 2 to 4. These studies suggest that both phenacetin and acetaminophen may contribute to the burden of ESRD, with the risk of the latter being somewhat less than that of the former. This apparent difference in risk may not be due to differences in nephrotoxic potential of the drugs themselves. A lower relative risk would be expected for acetaminophen if the risk of both drugs in combination with other analgesics was higher than the risk of either agent alone. Thus, acetaminophen has been used both as a single agent and in combination with other analgesics, whereas phenacetin was available only in combinations. The possibility that habitual use of acetaminophen alone increases the risk of ESRD has not been clearly demonstrated, but cannot be dismissed.

Measurement of glomerular filtration rate using nonradioactive Iohexol: comparison of two one-compartment models.

Radioisotopic methods for the determination of the glomerular filtration rate (GFR) are highly accurate but require the collection of multiple blood and urine samples and are costly to perform due to personnel, material, and analysis costs. Nonradioactive methods of GFR determination have the potential of minimizing procedure costs while preserving accuracy. We determined the GFR simultaneously by 125I-iothalamate and nonradioactive iohexol clearance methods in 41 adults. The study group consisted of 54% males, with a mean age of 50.7 (range 28-79) years and a mean GFR by 125I-iothalamate clearance of 66.5 +/- 28.3 (range 10-118) ml/min. The iohexol concentrations were measured by a simplified high-performance liquid chromatography method that did not require sample preparation. The iohexol plasma clearance was calculated by both a new one-compartment model as well as by Jacobsson's one-compartment model. Using Jacobsson's single-sample model and data from the 240-min point, there was an excellent correlation between 125 I-iothalamate and nonradioactive iohexol clearance values: r2 = 0.95, standard error of the estimate = 11.4 ml/min, and intrapatient coefficient of variation = 16.9%. However, this formula tended to overestimate GFRs < 30 ml/min and to underestimate GFRs > 80 ml/min. The new one-compartment model is a modification of Bubeck's model, originally used for the determination of renal plasma blood flow. Using this modified model, there was an excellent correlation between 125I-iothalamate and nonradioactive iohexol clearance values at all levels of GFR tested: r2 = 0.95, standard error of the estimate = 9.2 ml/min, and intrapatient coefficient of variation = 13.7%. In conclusion, the determination of the plasma clearance of iohexol by a nonradioactive technique and a monoexponential model is a simple and accurate method of determining the GFR in patients with varying degrees of renal impairment.

Pathophysiology of progressive renal failure.

Progressive renal failure is conditioned by a number of factors, including type of renal disease, sex, level of arterial pressure, insulin deficiency and/or hyperglycemia in diabetes mellitus, and dietary protein intake. Elevated arterial pressure may cause a progressive renal disease, hypertensive nephrosclerosis, and accelerate the rate of progression of all other chronic renal disease. Hypertension contributes to progressive renal failure by inducing myointimal hyperplasia of arcuate and afferent arterioles, causing glomerular ischemia, and by increasing pressure in the glomerular capillaries. The latter leads to hyperfiltration of protein, increased mesangial ingestion of protein, and glomerular sclerosis. Increased glomerular pressure may also be induced by protein feeding, insulin deficiency and hyperglycemia, especially in the presence of reduced nephron number. Thus at least one common mechanism underlies the effect of hypertension, protein feeding, and diabetes on the progression of chronic renal disease.

End-stage renal disease: can dietary protein restriction prevent it?

The hypothesis that dietary protein restriction slows the rate of progression of chronic renal disease has been tested in four large clinical trials, the largest and most elegant of which was the Modification of Diet in Renal Disease (MDRD) study conducted recently in the United States. During these trials the majority of patients with nondiabetic renal disease had slow progression, and no overall benefit from dietary intervention was demonstrated in three of four studies. However, MDRD is the first trial to suggest that protein restriction has a two-stage effect on renal function. During the first 4 months, glomerular filtration rate (GFR) fell more rapidly in patients with protein restriction than in patients with normal protein intake, probably because of a hemodynamic effect on the renal microcirculation. After this 4-month period, the rate of decline in GFR was slower in patients on the low protein diet. This suggests but does not prove that low protein diet may slow progression of renal disease in the long run. MDRD also showed that strict control of hypertension slows progression in patients with heavy proteinuria.

Renal biopsy findings in presumed hypertensive nephrosclerosis.

The 'classic' descriptions of renal histologic abnormalities in patients with hypertensive nephrosclerosis were based upon specimens obtained at autopsy or sympathectomy and were evaluated by light microscopy, without the aid of immunofluorescence or electron microscopy. Patients with renal insufficiency accompanied by elevated blood pressure, hypertensive target organ damage (retinal disease and left-ventricular hypertrophy) and mild proteinuria are typically labelled as having hypertensive nephrosclerosis in the absence of renal biopsy material. Herein, we report the clinical summaries and renal pathology from 2 patients initially diagnosed with hypertensive nephrosclerosis. Glomeruli exhibiting focal and segmental sclerosis and interstitial scarring were present in both cases. The presence of primary renal disease in patients felt to have hypertensive nephrosclerosis is likely more common than currently appreciated. This may result from the lack of renal histologic material and the late presentation of these patients to nephrologists. Misclassification of hypertensive nephrosclerosis would impact greatly on the epidemiology of end-stage renal disease and the evaluation and treatment of patients with chronic renal insufficiency.

The familial risk of end-stage renal disease in African Americans.

African Americans have higher overall incidence rates of end-stage renal disease (ESRD) compared with American whites. Hypertensive nephrosclerosis (HN), nephropathy secondary to diabetes mellitus types I and II, and chronic glomerulonephritis (CGN) all occur more frequently in African Americans. To explore the possibility that hereditary factors may play a role in the increased risk of ESRD in African Americans, the family history of 131 African American hemodialysis patients (cases) was compared with 115 age-, sex-, and race-matched non-ESRD controls. Odds ratios (ORs) were calculated to define the prevalence of a relative with ESRD among cases versus controls. Chi-square values were estimated from a log-linear model, while controlling for gender, to test for significance of ORs. Forty percent (12/30) of HN cases, 35% (18/51) of type II diabetes mellitus-induced renal failure cases, and 13% (5/38) of CGN cases had a first-, second-, or third-degree relative with ESRD. The presence of a first-degree relative with ESRD increased an African American's risk for developing ESRD ninefold (OR, 9.13; 95% confidence interval [CI], 2.6 to 31.8; P < 0.001). The presence of a first- or second-degree relative increased the risk fivefold (OR, 5.23; 95% CI, 2.2 to 12.3; P < 0.0002). First-, second-, or third-degree relatives with ESRD were more prevalent among cases with ESRD due to hypertension and type II diabetes mellitus compared with CGN (P < or = 0.05). Gender differences among the ORs were nonsignificant (P > 0.2) and socioeconomic class (level of education and income) did not differ markedly between cases and controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of phospholipids on renal function.

The effects of two classes of phospholipids (PL) on renal function have been studied. Bolus injections of 1 ng (10 pmol) of lysophosphatidylcholine (LPC) caused natriuresis and diuresis in rats. Natriuretic activity was eliminated by substituting unsaturated bonds in the 1-acyl group and by removing the choline group on the sn-3 position. Natriuretic activity was not affected by substitution of 1-alkyl for 1-acyl groups. In the dog, LPC was natriuretic when given as a bolus of 3.0 micrograms/kg or as a constant infusion at 5 ng/kg/min. To explore further the effect of alkyl PLs on renal function, a series of studies with platelet activating factor (PAF) was performed. PAF injected directly into the renal artery (IR) in bolus doses of 0.5-10 ng/kg caused renal vasodilation that was blocked by a specific PAF receptor antagonist. This effect was not due to release of vasodilatory eicosanoids, dopamine, or nitric oxide (NO). PAF given IR as a continuous infusion at 2.5 ng/kg/min attenuated the renal vasoconstrictor effects of angiotensin II and norepinephrine but not vasopressin. This effect to attenuate vasoconstriction was blocked by the NO inhibitor N-monomethyl-L-arginine. These studies using picomolar amounts of PL suggest a physiologic role for these compounds in control of renal function.