Quantifying exposure to calcium and phosphate in ESRD; predictive of atherosclerosis on top of arteriosclerosis?

BACKGROUND: Long-term exposure to hypercalcaemia and hyperphosphataemia leads to media calcification and predicts mortality in patients with end-stage renal disease (ESRD). It is debatable whether this exposure is only a risk factor for arteriosclerosis, or also for superimposed atherosclerosis. Calcium-phosphate exposure is difficult to quantify, because it is variable in time and exerts its deleterious effects only after prolonged presence. METHODS: In 90 dialysis patients, calcium and phosphate values from the complete dialysis period were collected. From three-month averages, measures for calcium-phosphate exposure were derived after exclusion of transplant periods. Calcium-phosphate exposure was then related to intima-media thickness (IMT) and to ankle-brachial index (ABI) as markers of early atherosclerosis. RESULTS: Calcium-phosphate exposure was quantified in three ways using 1670 patient-quarters (i.e. three-months periods) covering 93% of the time on dialysis: averaged calcium-phosphate exposure, percentage of time with above-reference values, and burden of hypercalcaemia/hyperphosphataemia represented by this percentage multiplied by months on dialysis. No association was found with IMT. Patients with increased, not decreased, ABI had higher calcium-phosphate exposure throughout dialysis treatment: hyperphosphataemia burden was 31 (19 to 43) months for patients with ABI between 0.90 and 1.40 and 79 (58 to 100) months for patients with ABI >1.40 or incompressible ankle arteries (p<0.001). CONCLUSION: These findings do not support the hypothesis that calcium-phosphate exposure leads to atherosclerotic changes on top of arteriosclerosis in ESRD, and confirm its role in causing arteriosclerotic damage leading to increased arterial stiffness and incompressible ankle arteries. The used tool for quantifying calcium-phosphate exposure is easy to apply and can properly weigh the complete exposure during ESRD.

Patients' representations of their end-stage renal disease: relation with mortality.

BACKGROUND: Self-regulation theory explains how patients' illness perceptions influence self-management behaviour (e.g. via adherence to treatment). Following these assumptions, we explored whether illness perceptions of ESRD-patients are related to mortality rates. METHODS: Illness perceptions of 182 patients participating in the NECOSAD-2 study in the period between December 2004 and June 2005 were assessed. Cox proportional hazard models were used to estimate whether subsequent all-cause mortality could be attributed to illness perception dimensions. RESULTS: One-third of the participants had died at the end of the follow-up. Mortality rates were higher among patients who believed that their treatment was less effective in controlling their disease (perceived treatment control; RR = 0.71, P = 0.028). This effect remained stable after adjusting for sociodemographic and clinical variables (RR = 0.65, P = 0.015). CONCLUSIONS: If we consider risk factors for mortality, we tend to rely on clinical parameters rather than on patients' representations of their illness. Nevertheless, results from the current exploration may suggest that addressing patients' personal beliefs regarding the effectiveness of treatment can provide a powerful tool for predicting and perhaps even enhancing survival.

Acute effects of hemodialysis on salivary flow rate and composition.

AIMS: To evaluate acute effects of hemodialysis (HD) on the salivary flow rate, pH and biochemical composition before, during and after completion of a dialysis session. MATERIAL AND METHODS: Unstimulated whole saliva (UWS) and chewing-stimulated whole saliva (CH-SWS) were collected in 94 HD patients. Salivary flow rate, pH, concentrations of total protein, albumin, cystatin C, secretory immunoglobulin A (S-IgA) and of sodium, potassium and urea were measured. RESULTS: HD had an acute stimulating effect on the salivary flow rate (UWSbefore = 0.30+/-0.22 ml/min, UWSduring = 0.39+/-0.25 ml/min, p < 0.005). The mean pH of UWS showed a small but significant increase during HD mainly due to an increased watery secretion from the salivary glands. The salivary biochemical constituents changed markedly, but no significant difference in output was found. The electrolyte concentration did not change significantly during dialysis. The level of urea in CH-SWS declined to 40% (Ureabefore = 25.+/-6.4 mmol/l, Ureaduring = 15.3+/-4.5 mmol/1). CONCLUSIONS: This study shows that HD has significant acute effects on both salivary secretion rate and protein concentrations in saliva. We conclude that the observed changes in salivary concentrations and proteins are mainly due to an increased watery secretion from the salivary glands.

Long-term blood pressure monitoring and echocardiographic findings in patients with end-stage renal disease: reverse epidemiology explained?

BACKGROUND: In patients with end-stage renal disease (ESRD) hypertension is common and often leads to left ventricular (LV) hypertrophy and diastolic dysfunction, but hypotension at the onset of dialysis is associated with increased mortality. We studied blood pressure data over longer periods of time in patients on haemodialysis and related them to echocardiographic outcome, in order to elucidate these contradictory findings. METHODS: In 50 haemodialysis patients mean arterial pressure (MAP) and pulse pressure (PP) were calculated in the first three months of haemodialysis, the complete period from the start of haemodialysis until echocardiography and the last three months of haemodialysis before echocardiography. Hypertension load, pulse pressure and interdialytic weight gain were quantified and related to echocardiography. RESULTS: LV mass index was associated with MAP in all three periods, and also with the hypertension load, PP and PP load. In patients with LV dilatation, MAP and PP averaged over the complete period of dialysis were 5 to 7 mmHg higher than in patients without LV dilatation. Blood pressure parameters were the same in patients with or without LV diastolic dysfunction or systolic dysfunction. Systolic dysfunction was more frequent in patients undergoing long-term haemodialysis treatment. Interdialytic weight gain was not associated with any of the echocardiographic variables. CONCLUSION: When long-term blood pressure values are considered, hypertension is associated with parameters of early cardiac damage such as increased LV mass index and not with parameters of advanced heart failure such as systolic dysfunction. This supports the hypothesis that the presence of advanced heart failure reciprocally influences blood pressure in a negative way, thereby explaining the 'reverse epidemiology' of blood pressure and mortality in ESRD.

Rare cause of ureteral stenosis more than 10 years after kidney transplantation.

Late renal graft failure is in most cases due to a chronic allograft nephropathy. In this report, we present a case in which a surgical complication led to ureteral stenosis more than 10 years after transplantation. The patient developed slowly deteriorating renal function and ultimately progressive hydronephrosis. At surgical exploration, the ureter was found to perforate the wall of the small bowel before entering the bladder. We successfully performed ureter reimplantation to restore the outflow of the kidney.

Hemodialysis (HD) versus peritoneal dialysis (PD): latent overhydration in PD patients?

Data on the difference in fluid status between hemodialysis (HD) and peritoneal dialysis (PD) patients are scarce. Bio-electrical impedance analysis (BIA) is able to detect total body water (TBW) and its distribution in intracellular (ICW) and extracellular water (ECW). Echographic determination of the diameter of the inferior caval vein (VCD) provides information about the intravascular space (IVS). Nineteen PD-patients and 20 HD-patients in stable clinical condition were studied. In HD-patients a significant decrease in VCD, mean arterial pressure (MAP), TBW and ECW was noted due to ultrafiltration. Both ratios of VCD to ICW/ECW and of VCD to ECW/TBW decreased. No significant differences were found in these variables between PD-patients and HD-patients before HD. In both patient groups the measured variables pointed towards overhydration and the increased ratios both of VCD to ICW/ECW and VCD to ECW/TBW towards the storage of surplus of fluid in the intravascular space. It can be concluded that both PD-patients and HD-patients before HD have a surplus of fluid in the extracellular compartment, predominantly stored in the intravascular space.

Clinical outcome of daily dialysis.

Dialysis patients are prone to malnutrition, which may be counteracted by daily home hemodialysis (DHHD, 6 times a week) due to improved clinical outcome and quality of life. Eleven patients were treated with DHHD during 18 months, after a run-in period with three dialysis sessions a week. The total weekly dialysis dose was kept constant during the first 6 months of DHHD, whereupon it was allowed to increase. KT/V was 3.1 +/- 0.5 at baseline, 3.2 +/- 0.5 after 6 months and 4.0 +/- 0.8 at 18 months. Blood pressure decreased from 142 +/- 19/83 +/- 8 to 130 +/- 25/79 +/- 9 mmHg with a more than 50% reduction in antihypertensive medication. Potassium did not change, but potassium binding resins could be stopped almost completely. Bicarbonate increased from 20.6 +/- 3.3 to 23.1 +/- 2.6 mEq/L after 18 months. Patients with a protein intake of less than 1.0 g/kg/d showed a greater increase in body weight (62.3 +/- 6.0 to 65.5 +/- 3.7, P: < 0.05) and normalized protein catabolic rate (nPCR) (0.87 +/- 0.08 to 1.25 +/- 0.36, ns) than patients with acceptable protein intake (>/=1.0 g/kg/d). Phosphate decreased, though not significantly, especially in the latter group. Erythropoietin dose could be reduced from 6400 +/- 5400 U/L at baseline to 5100 +/- 4000 U/L at 18 months. Quality of life improved significantly, especially with to respect to physical condition and mental health. The DHHD markedly improves hemodynamic control and quality of life. Overall nutritional parameters did not change, except cholesterol. Patients with a low protein intake, however, showed a significant increase in body weight, and a greater rise in nPCR.

Diameter of inferior caval vein and impedance analysis for assessment of hydration status in peritoneal dialysis.

In 19 stable peritoneal dialysis (PD) patients, hydration status was evaluated by measurement of vena cava diameter (VCD) and bioelectrical impedance analysis (BIA) variables: intracellular water (ICW), extracellular water (ECW), and total body water (TBW). We investigated whether BIA can replace VCD. VCD did not correlate with TBW but correlated moderately with ECW/TBW (r = 0.42; 0.025 < p < 0.05) and ICW/ECW (r = -0.47; p < 0.025). Patients with underhydration (n = 4; VCD <8 mm/m2) revealed limits for BIA variables as ICW/ECW (>1.50) and ECW/TBW (<0.40). The same held true for overhydration (n = 5; VCD >11.5 mm/m2): ICW/ECW (<1.50) and ECW/TBW (>0.40). Although the positive predictive value of ICW/ECW and ECW/TBW for both under- and overhydration was only 50% and 54%, respectively, there were no false negative values. Although BIA cannot replace VCD in PD patients, the reverse holds true as well. Combining BIA and VCD may lead to a better estimation of hydration status because both techniques provide complementary information.

The impact of equations on calculation of lean body mass by bioelectrical impedance analysis in RDT patients.

Several equations are available to derive lean body mass (LBM) from bioelectrical impedance analysis (BIA). The purpose of this study was to investigate in dialysis patients the impact of the equation used on the outcome of LBM assessment. To avoid dyshydration as a confounder, vena cava diameter measurement was used to assess normohydration in the 21 patients studied. Five equations were compared. In a previously published study to assess total body water using antipyrine as a gold standard, Deurenberg's formula was advocated to be used in the estimation of LBM by BIA. Therefore, this formula was used as a basis for comparison with the other four equations. One equation gave results comparable to those obtained by Deurenberg's formula. Despite high correlations and agreement according to Bland and Altman analysis, the other three equations showed a significant difference with Deurenberg-derived LBM. Thus, the equation used has a major impact on the outcome of LBM estimations.

Daily home haemodialysis in The Netherlands: effects on metabolic control, haemodynamics, and quality of life.

BACKGROUND: More frequent dialysis has been claimed to improve clinical outcome and quality of life. METHODS: Clinical status was optimized in 13 haemodialysis patients during a run-in period of 2 months with three dialysis sessions a week. Thereafter, daily home haemodialysis (DHHD, 6 sessions per week) was initiated. The total weekly dialysis dose (Kt/V) was kept constant. RESULTS: Weekly Kt/V was 3.2+/-0.13 (M+/-SEM) before, and 3.2+/-0.15 after 6 months of DHHD (NS), time-averaged concentration of urea (TACu) was 21.2+/-1.6 mmol/l and 20.1+/-0.9 mmol/l (NS). Urea reduction was 0.56+/-0.05 before DHHD, and 0.41+/-0.06 during DHHD (P<0.0001). Serum K remained unchanged, but significantly less exchange resins were used (P<0.02). Also, the dose of phosphate-binding agents could be decreased. Values for Na, K, Cl, bicarbonate, Ca, PTH, albumin, and Hb remained unchanged. Iron deficiency developed in some patients. Twenty-four-hour blood pressure monitoring showed a decrease of systolic blood pressure (141.1+/-17.2 mmHg before, and 130.9+/-19.2 mmHg during DHHD, P<0.001). Diastolic blood pressure remained constant (82.8+/-7.2 and 76.9+/-10.1 mmHg, NS). Mean arterial pressure decreased from 102.2+/-9.5 to 94.9+/-1.4 mmHg (P<0.02). Blood pressure decreased mainly in previously hypertensive patients. Mean target weight increased 0.8 kg. The amount of antihypertensive drugs used decreased from 1.88+/-0.35 to 0.75+/-0.17 (P<0.005, n=7). Dialysis sessions were much more stable, also in patients with cardiac insufficiency. Quality of life questionnaires (Rand 36, Nottingham Health Profile, Uraemic Symptoms Profile) showed a significant improvement of physical condition and fewer uraemic symptoms. CONCLUSION: DHHD compared to conventional thrice-weekly haemodialysis with similar weekly Kt/V results in an improved haemodynamic control and quality of life, but has lesser impact on metabolic regulation.

High-flux dialysis membranes improve lipid profile in chronic hemodialysis patients.

In a controlled prospective trial, the effect of a switch from cellulose-based, low-flux dialysis membranes to polysulphone, high-flux membranes on lipid parameters was evaluated. Baseline values of lipid parameters were identical in the study group and the control group in which the dialysis membrane remained unchanged. After 6 wk, total triglyceride, very low-density lipoprotein (VLDL) triglyceride, and VLDL cholesterol decreased, respectively, 28 +/- 17 (P < 0.01), 38 +/- 17 (P < 0.01), and 24 +/- 21% (P < 0.05), and the proportion of total cholesterol that was high-density lipoprotein cholesterol increased from 15 +/- 5 to 18 +/- 5% (P < 0.05) in the high-flux polysulphone group, whereas these variables remained unchanged in the control group. Low-density lipoprotein and total cholesterol as well as Kt/V, protein catabolic rate, parathyroid hormone, albumin, and body weight did not change. No change in lipoprotein lipase activity was found. In a second study, the effects of a single hemodialysis session with high-flux polysulphone and low-flux, cellulose-based membranes on lipid parameters and lipolytic activity were compared in a cross-over fashion. Treatment with both membranes resulted in a significant decrease in plasma triglyceride, VLDL triglyceride, and VLDL cholesterol. Lipoprotein lipase activity increased during hemodialysis. Changes in lipid parameters and lipolytic activity were identical during the two treatments.

Efficacy of intrarenal ACE-inhibition estimated from the renal response to angiotensin I and II in humans.

Recent studies on the nature of the renin-angiotensin system (RAS) in animals have led to the concept that systemic and intrarenal RAS can be influenced to different degrees by angiotensin converting enzyme (ACE) inhibitors. Assessment of efficacy of intrarenal ACE inhibition by ACE inhibitors in humans is necessarily indirect and has not been reported. We therefore monitored the renal response to acute angiotensin (Ang) I infusion in volunteers taking 20 mg enalapril twice daily, and related the responses to the obtained increments in plasma Ang II levels. Ang I infusion rates of 4, 8, 16, and 32 pmol/kg/min caused gradual increments in plasma Ang I (maximal change from 26 +/- 18 to 578 +/- 120 pmol/liter, P < 0.05) and, despite treatment with enalapril, also of Ang II (from 3 +/- 1 to 29 +/- 5 pmol/liter, P < 0.05). This was associated with large reductions in renal plasma flow (paraaminohippurate clearance), filtration fraction, maximal urine flow, sodium excretion, lithium and uric acid clearance, and increments in mean arterial pressure and plasma aldosterone (P < 0.05 for each variable). Strong correlations existed between the changes in either variable and the increment in plasma Ang II. Infusions of Ang II at 1 and 4 pmol/kg/min in the same subjects caused comparable increments in plasma Ang II and had similar physiological effects as found during the Ang I infusion. Analysis of covariance of the changes in plasma Ang II and each of the measured variables revealed no differences between Ang I and Ang II infusions.(ABSTRACT TRUNCATED AT 250 WORDS)

The origin of urinary angiotensins in humans.

To examine whether urinary angiotensin (ANG) I and II excretion responds to changes in plasma ANG I and ANG II, ANG I or ANG II was infused in seven healthy subjects pretreated with a 340-mmol sodium diet and 20 mg of enalapril twice daily. Infusion rates were 4, 8, 16, and 32 pmol/kg per minute for ANG I and 1, 4, and 8 pmol/kg per minute for ANG II. Baseline ANG I and ANG II excretions averaged 10 and 20 fmol/min, respectively, which is approximately 0.3 and 5% of the filtered loads. Despite a 20-fold increase in plasma ANG I during ANG I infusion, urinary ANG I did not increase. Similarly, the 30-fold increase in plasma ANG II during ANG II infusion was not followed by an increase in ANG II excretion, but in fact by a decrease in urinary ANG I and ANG II. In a separate study, urinary ANG I and ANG II were measured before and after the oral administration of 20 mg of enalapril in eight healthy volunteers taking 400, 200, or 20 mmol of NaCl daily. In contrast to the considerable effects on plasma ANG I and ANG II and renal hemodynamics, enalapril had no effect on urinary ANG I and ANG II. Variation of sodium intake had predictable effects on plasma ANG I and ANG II but did not affect urinary ANG I and ANG II. These data suggest that urinary ANG I and ANG II originate from an intrarenal source. The independency of sodium intake and ANG-converting enzyme make the juxtaglomerular apparatus as the site responsible for the production of this ANG unlikely.

Posttransplant T-cell lymphoma. Report of three cases and a review of the literature.

BACKGROUND: Although 14% of the malignant lymphomas after organ transplantation are reported to be T-cell lymphomas, only a few cases are described in the literature. METHODS: The authors presented three new cases. They summarized the clinical data and analyzed histologic and immunochemical findings. The presence of Epstein-Barr virus (EBV) and human T-cell lymphoma type 1 (HTLV-1) were investigated. T-cell receptor (TCR) rearrangement was analyzed by Southern blot technique in two cases. RESULTS: Two of the three lymphomas developed after renal transplantation. One was a T-cell lymphoma of pleomorphic medium-sized cell type and the other was a T-cell lymphoblastic lymphoma; the third T-cell lymphoma was an anaplastic large cell (Ki-1 positive) type that developed after heart transplantation. No association was established with EBV or HTLV-1. A monoclonal TCR rearrangement was found in the two cases that were analyzed. A literature search revealed 22 other cases. Nineteen of the 22 reported cases were peripheral T-cell lymphomas. Almost all lymphomas presented in extra-nodal sites. The time between diagnosis and organ transplantation seemed to be influenced by the type of immunosuppressive therapy. In five cases, EBV was detected in the tumor cells. A monoclonal T-cell receptor rearrangement was found in eight cases and a polyclonal proliferation in one case. Response to therapy was variable, but often poor. CONCLUSIONS: The etiology of posttransplant T-cell lymphomas remains unclear. Similarities with posttransplant B-cell proliferations are the predominant extranodal presentation and the finding that the time of occurrence is influenced by the type of immunosuppression. In contrast with posttransplant B-cell proliferations, only a minority of the cases are associated with EBV. Most tumors appear to be monoclonal. Prognosis is generally poor, but tumor presentation with localized disease might have a somewhat better prognosis.

[Little difference in quality of life of dialysis patients in Utrecht and Willemstad]. / Kwaliteit van leven van dialysepatiënten in Utrecht en Willemstad weinig verschillend.

OBJECTIVE: To assess and compare the quality of life of patients treated with haemodialysis and chronic ambulatory peritoneal dialysis (CAPD) in Utrecht and Willemstad, Curaçao. DESIGN: Transverse multicentre study. METHODS: All haemodialysis and CAPD patients in Utrecht and all haemodialysis patients in Curaçao under treatment for over 6 months were studied. The objective tests applied were the 'Nottingham health profile', the 'affect balance scale', the 'index of well-being' and the 'Amsterdam complaint profile'. Possible correlations between individual patient-related and treatment-related factors and biochemical variables were also investigated. RESULTS: The objective and subjective tests revealed only slight differences in quality of life in the three groups. In a few respects, the CAPD patients rated the quality of life slightly better. In the Utrecht group a positive relationship was seen between haematocrit (higher owing to treatment with erythropoietin) and plasma bicarbonate concentration, and the quality of life.

Effects of enalapril on renal sodium handling in healthy subjects on low, intermediate, and high sodium intake.

Angiotensin-converting enzyme (ACE) inhibitors have a modest natriuretic effect, but the responsible changes in tubular sodium (Na) handling are not fully known. We therefore studied the effect of a single dose of 20 mg enalapril on Na excretion in 8 healthy subjects, using lithium clearance and maximal water diuresis to analyze tubular Na handling. Because the natriuretic effect may depend on the volume state, the same subjects were studied during low (20 mmol Na/day), medium (200 mmol Na/day), and high (400 mmol Na/day) salt intake. Enalapril caused natriuresis during the 20-mmol Na diet (from 51 +/- 9 to 81 +/- 14 mumol/min, p < 0.05) and the 200-mmol Na diet (from 190 +/- 24 to 230 +/- 31 mumol/min, p < 0.05), but not during the 400-mmol Na diet. The increase in Na excretion was not accompanied by consistent changes in glomerular filtration rate (GFR), free water clearance data, maximal urine flow, uric acid clearance, or lithium clearance. Instead, the increase in Na excretion was positively related to the increase in Na concentration in the maximally diluted urine (r = 0.75, p < 0.01). Regardless of diet, enalapril reduced the filtration fraction, but a significant increase in effective renal plasma flow was noted only during the 20-mmol Na diet. The data suggest that a decrease in Na reabsorption in the diluting segment, perhaps related to renal vasodilatation, participates in the natriuretic effect of ACE inhibition in humans.

Effects of angiotensin II on renal sodium handling and diluting capacity in man pretreated with high-salt diet and enalapril.

The antinatriuretic effect of angiotensin II (Ang II) is generally attributed to a decreased glomerular filtration rate (GFR) and an increased proximal tubular sodium reabsorption. We studied this by infusion of increasing amounts (1, 4, and 8 pmol/kg per min) of Ang II in seven water-loaded volunteers who were pretreated with enalapril and a high-salt diet. While mean arterial pressure increased from 92 +/- 3 mmHg to respectively 98 +/- 3, 110 +/- 2, and 116 +/- 2 mmHg, sodium excretion fell from 331 +/- 40 to 135 +/- 23, 65 +/- 17, and 63 +/- 22 mumol/min, and GFR from 138 +/- 9 to 128 +/- 6, 111 +/- 6, and 104 +/- 8 ml/min (P < 0.05 for each variable). At 1 pmol/kg per min, Ang II decreased maximal urine flow and the fractional excretions of lithium and uric acid. Urine sodium concentration decreased, whereas minimal urine osmolality remained unchanged. At 4 pmol/kg per min, these effects were more pronounced. Moreover, minimal urine osmolality increased from 58 +/- 4 to 72 +/- 8 mosm/kg, but sodium concentration decreased further. The step to 8 pmol/kg per min did not decrease sodium, lithium, or uric acid excretion further, but induced a further increase in minimal urine osmolality to 99 +/- 16 mosm/kg. These data suggest that the antinatriuretic effect of modestly hypertensive dosages of Ang II is not only due to a decrease in GFR and an increase in proximal sodium reabsorption, but also involves a rise in fractional reabsorption in a distal nephron segment. In addition Ang II decreases renal diluting capacity.(ABSTRACT TRUNCATED AT 250 WORDS)

Response of urinary angiotensin to challenges of the renin-angiotensin system.

Angiotensin has an intrarenal action which may not parallel its action in the general circulation. We investigated whether the urinary excretion rates of angiotensin I and II (UV-AI, UV-AII) can be used as a marker of renal production. We therefore measured UV-AI, UV-AII, plasma angiotensin I and II (PAI, PAII), and plasma renin activity (PRA) in healthy subjects under conditions influencing the renin-angiotensin system: captopril injection (n = 7), enalapril treatment (n = 9), furosemide infusion on high and low sodium intake (n = 6), indomethacin treatment (n = 8), and head-out water immersion (three sodium intakes). After captopril (acute) and enalapril (chronic), PAI and PRA increased, PAII decreased, but neither UV-AI nor UV-AII changed. During furosemide infusion, PAI, PAII, PRA, as well as UV-AI and UV-AII increased. During indomethacin treatment, PAI, PAII, and PRA decreased, whereas UV-AI and UV-AII did not change consistently. Sodium restriction increased PAI, PAII, and PRA, but did not alter UV-AI and UV-AII. Head-out immersion decreased PAI, PAII, and PRA, but did not change UV-AI and UV-AII. The relative constancy of the urinary AI and AII excretion rates makes it doubtful whether urinary angiotensins reflect changes of renal angiotensin production.