David J. Hirsch

Interrelations among blood pressure, blood volume, plasma renin activity and urinary catecholamines in benign essential hypertension☆

Interrelations among blood pressure, circulatory volume, plasma renin activity (PRA) and urinary catecholamine excretion rates were studied in normal subjects and in patients with benign essential hypertension. Mean plasma or blood volumes related to lean body mass, products of blood volume and the logarithm of PRA, and catecholamine excretion rates did not differ significantly between normal and hypertensive subjects. In both normal subjects and hypertensive patients, blood pressure levels correlated positively with the noradrenaline excretion rate (r = 0.40 and 0.36, respectively; p less than 0.025) but not with adrenaline excretion, circulatory volume or the volume-renin product. The logarithm of PRA correlated inversely with mean blood pressure in normal subjects (r = 0.40; p less than 0.001) but not in hypertensive patients; however, there was no convincing evidence for an inappropriate blood pressure-PRA relationship as a prominent feature in the hypertensive patients. PRA did not correlate with blood volume. Patients with low PRA relative to sodium excretion (21 per cent of hypertensive population) were consistently normovolemic, but they tended to be older and excreted less (p less than 0.025) adrenaline than patients with normal or high PRA. The patient subgroup with high PRA relative to sodium excretion (11 per cent of population) was hypovolemic (p less than 0.02); despite this, urinary sodium output was high (172 +/- 64 meq/24 hours). These data reveal no evidence for major roles of PRA, circulatory volume and free peripheral catecholamines in the maintenance of benign essential hypertension. Essential hypertension with low PRA is usually not a hypervolemic state, but it may reflect diminished adrenergic activity, factors associated with aging and effects of a high systemic pressure. High PRA in benign essential hypertension may be at least partly a consequence of hypovolemia resulting from high blood pressure-induced sodium diuresis.

Economic appraisal of maintenance parenteral iron administration in treatment of anaemia in chronic haemodialysis patients

BACKGROUND Iron deficiency is common in haemodialysis patients and adequate supplementation by the oral or parenteral route has been limited by drug side-effects, absorption, and cost. Intermittent doses of intravenous iron dextran complex are recommended in patients with inadequate iron stores despite maximal tolerated oral dose. We conducted a prospective study with economic analysis of a regular maintenance intravenous iron regimen in this group of patients. METHODS Fifty patients comprising one-half of our haemodialysis population required intravenous iron treatment, i.e. they failed to achieve an arbitrary goal serum ferritin 100 microg/l despite maximal tolerated oral iron dose. After a loading dose of intravenous iron dextran complex (IV-FeD) based on Van Wycks nomogram (400+/-300 mg) they received a maintenance dose of 100mg IV-FeD once every 2 weeks. Initial goal serum ferritin was set at 100-200 microg/l. If no increase in haemoglobin was achieved at this level, transferrin saturation was measured to assess bioavailable iron, and when less than 20%, goal serum ferritin was increased to 200-300 microg/l. Recombinant human erythropoietin (rHuEpo) was used where needed to maintain haemoglobin in the 9.5-10.5 g/l range only if ferritin requirements were met. Results. Mean haemoglobin rose from 87.7+/-12.1 to 100.3+/-13.1 g/l (P<0.001, Cl 7.7-17.9) at mean follow-up of 6 months (range 3-15 months). In patients on rHuEpo, dose per patient was reduced from 96+/-59 u/kg per week to 63+/-41 u/kg per week, representing a 35% dose reduction (P<0.05, Cl 1-65). An annual cost reduction of

Experience with not offering dialysis to patients with a poor prognosis

3166 CDN was projected; however, in the first year this is offset by the cost of the loading dose of IV-FeD required at the beginning of treatment. No adverse reactions were encountered. CONCLUSION Iron deficiency is very common in our haemodialysis population, especially in those patients receiving rHuEpo. A carefully monitored regimen of maintenance parenteral iron is a safe, effective, and economically favourable means of iron supplementation in patients with insufficient iron stores on maximum tolerated oral supplements.

CLINICAL PRACTICE GUIDELINES AND RECOMMENDATIONS ON PERITONEAL DIALYSIS ADEQUACY 2011

Despite ongoing discussion of dialysis rationing in the nephrology community, there are little available data describing current practice in treatment selection for very ill renal patients with a poor prognosis. We report a prospective survey of end-stage renal patients referred to our Canadian regional dialysis center who were not accepted to the dialysis program on the grounds of poor prognosis and low quality of life. One quarter of patients referred during 1992 were not accepted to the program, with a mean age of 74 +/- 11 years. Patients were predominantly female and most suffered from a combination of renovascular and cardiovascular disease, with very poor functional capacity as determined by the Karnofsky scale. Nonacceptance to the dialysis program did not create legal difficulties or requests for second opinions. Based on our experience, we propose guidelines for nonacceptance of patients to dialysis programs.

Curable Hypertension with Unilateral Hydronephrosis: Studies on the Role of Circulating Renin

Division of Nephrology,1 University of Western Ontario, London, Ontario; Division of Nephrology,2 University of Toronto, Toronto, Ontario; Division of Nephrology,3 McMaster University, Hamilton, Ontario; Division of Nephrology and Transplant Immunology,4 University of Alberta, Edmonton, Alberta; Division of Nephrology,5 Dalhousie University, Halifax, Nova Scotia; Division of Nephrology,6 University of Ottawa, Ottawa, Ontario; Division of Nephrology,7 University of British Columbia, Vancouver, British Columbia, Canada

Best Threshold for Diagnosis of Stenosis or Thrombosis within Six Months of Access Flow Measurement in Arteriovenous Fistulae

Among eight patients with unilateral hydronephrosis and hypertension, peripheral plasma renin activity was normal in seven and borderline high in one. Four patients had hydronephrotic/contralateral kidney renin ratios of greater than 1.5, suggesting excessive renin release from the diseased kidney, and ratios between contralateral kidney and peripheral blood of less than 1.2, indicating suppressed renin production in the contralateral kidney. Nephrectomy normalized blood pressure in each of these patients. Two patients had hydronephrotic/contralateral kidney renin ratios of less than or equal to 1.3 or contralateral kidney/periphery ratios of greater than 1.2, suggesting ischemia of the contralateral kidney; pyeloplasty or nephrectomy, or both, failed to improve the hypertension. Postoperative changes in blood pressure correlated with changes in peripheral renin (r = 0.90; P less than 0.01). These data suggest that hypertension associated with unilateral hydronephrosis is partly renin-dependent; and renal vein renin values are helpful in selecting patients for surgery.

Crescentic IgA Nephropathy as a Manifestation of Human Immune Deficiency Virus Infection

Canadian clinical practice guidelines recommend performing angiography when access blood flow (Qa) is <500 ml/min in native vessel arteriovenous fistulae (AVF), but data on the value of Qa that best predicts stenosis are sparse. Because correction of stenosis in AVF improves patency rates, this issue seems worthy of investigation. Receiver-operating characteristic curves were constructed to examine the relationship between different threshold values of Qa and stenosis in 340 patients with AVF. Stenosis was defined by the composite outcome of access failure or angiographic stenosis occurring within 6 mo of the first Qa measurement. The Qa value was then classified as true negative, true positive, false negative, or false positive for stenosis. An additional analysis was performed in which Qa was corrected for systolic BP before assigning it to one of the four diagnostic categories. The area under the curve for the composite definition of stenosis was 0.86. Graphically, Qa thresholds of <500 and <600 ml/min had similar efficacy for detecting stenosis or access failure within 6 mo, and both seemed superior to <400 ml/min. However, the frequency of the composite definition of stenosis among AVF with Qa between 500 and 600 ml/min was only 6 (25%) of 24, as compared with 58 (76%) of 76 when Qa was <500 ml/min. This suggests that most lesions that would be found using a threshold of <600 ml/min occurred in AVF with Qa <500 ml/min and that the small gain in sensitivity associated with the <600-ml/min threshold would be outweighed by the reduced specificity compared with <500 ml/min. Correcting Qa for BP did not improve diagnostic performance or change these results, which were consistent in several sensitivity analyses. Qa measurements seemed to predict stenosis or incipient access failure equally well in groups defined by diabetic status, gender, and AVF location. In conclusion, it was found that Qa <500 ml/min seems to be the most appropriate threshold for performing angiography in patients with native vessel AVF. It is recommended that clinicians arrange angiography when Qa is <500 ml/min in AVF.

Access Flow Monitoring of Patients with Native Vessel Arteriovenous Fistulae and Previous Angioplasty

A 37-year-old Caucasian male homosexual presented with hematuria and rapidly progressive acute renal failure. He was found to have proteinuria and microscopic hematuria as well as RBC casts. Investigations revealed polyclonal gammopathy with five times normal serum IgA levels as well as elevated serum IgG. Renal biopsy showed evidence of crescentic IgA nephropathy with ultrastructural changes of tubuloreticular inclusions described in HIV nephropathy. He was found to be positive for human immunodeficiency viral antibodies. Renal function improved during follow-up after two doses of 1 g each of methylprednisone. In our opinion, this is the first case of HIV-related crescentic IgA nephropathy. HIV testing should be performed more frequently in patients presenting with acute glomerular diseases.

Relation between access blood flow and mortality in chronic hemodialysis patients.

Screening strategies based on measurement of access blood flow (Qa) allow detection and angioplasty of subclinical stenosis in native vessel arteriovenous (AV) fistulae. However, little is known about the efficacy of Qa measurements for detecting recurrent stenoses in fistulae and that of angioplasty for correcting them. A total of 303 patients were studied over 30 mo; 69 (23%) of these had stenoses, of whom 53 underwent angioplasty. Of those undergoing angioplasty, 30 patients had 46 episodes of recurrent positive studies and underwent repeat fistulography. In 31 of these episodes (19 patients), stenosis was again identified and treated successfully with angioplasty. Overall positive predictive values for stenosis were similar in first and subsequent episodes of stenosis (71% versus 67%), and angioplasty was associated with sustained increases in Qa for both first and subsequent episodes. Assisted patency in fistulae that required repeat angioplasty was 87% (median follow-up 10 mo after the second angioplasty). In conclusion, Qa is effective for detecting first and subsequent lesions in patients with AV fistulae, and angioplasty of first or subsequent lesions is associated with sustained increments in Qa. Continued screening after correction of first stenoses appears reasonable, because of both the frequency of recurrent stenosis and the success of repeat intervention.

Acute skin and fat necrosis during sepsis in a patient with chronic renal failure and subcutaneous arterial calcification

BACKGROUND Access blood flow (Qa) measurement is a potentially important determinant of systemic hemodynamics in hemodialysis patients. High Qa may contribute to left ventricular dilation and high output heart failure. On the other hand, low Qa might lead to underdialysis, which is associated with adverse outcomes. METHODS In this retrospective study of incident chronic hemodialysis patients treated in three Canadian cities (Edmonton, Calgary, and Halifax), the hypothesis that extremes of Qa(low or high) would be associated with increased mortality was tested. The distribution of Qa was not Gaussian, and therefore Qa was log-transformed in analyses that treated it as a continuous variable. Qa was classified into categories defined by cutpoints of 500, 1000, 1500, and 2000 ml/min. Univariate and multivariate Cox proportional hazard models were performed to examine the relation between Qa and all-cause mortality. Patients were followed from the date of Qa measurement until death; follow-up was discontinued at loss to follow-up, kidney transplantation, or end of study. RESULTS Of 820 participants, those with lower levels of Qa tended to be older and to have more comorbidities. During the median follow-up period of 28 mo, 206 (25.1%) participants died and 101 (12.3%) patients received a kidney transplant. When only baseline measures of Qa were considered, there was significant association between Qa and mortality [hazard ratio (HR) per unit increase in logQa 0.81, 95% confidence interval (CI) 0.67, 0.97; adjusted HR per unit increase in logQa 0.90, 95% CI 0.72, 1.11]. The adjusted risk of mortality was similar between the different categories of baseline Qa before and after adjustment for demographic characteristics, comorbidity, and access type. In analyses that included all Qa measurements per patient as a time-varying covariate, the adjusted association between Qa and death remained nonsignificant, with no evidence of increased mortality at higher Qa (HR per unit increase in logQa 0.82, 95% CI 0.67, 1.01, P = 0.066). CONCLUSION The findings of this study do not suggest an increased risk of death at higher levels of Qa, Further studies would be needed to confirm an increased risk of death at lower Qa.