Inaccuracies in estimated glomerular filtration rate in one Australian renal centre.

BACKGROUND: Early identification of true renal disease (glomerular filtration rate (GFR) < 60 mL/min) results in better patient outcomes. There is now routine reporting in Australia of estimated GFR (eGFR) in all patients over age 18 who have serum creatinine measured, calculated by the Modification of Diet in Renal Disease (MDRD) formula, which was validated in an American Caucasian cohort. Significant clinical decisions and prognosis are often made on the basis of this calculation. AIM: To assess the accuracy of three estimates of GFR in an Australian population by comparing eGFR obtained by the abbreviated MDRD (aMDRD), Cockcroft-Gault corrected for body surface area (BSA) (CG) and Chronic Kidney Disease Epidemiology (CKD-Epi) formulae with a gold standard, isotopic (51) Cr-ethylenediaminetetra-acetic acid ((51) Cr-EDTA) GFR. METHODS: Patients referred with an eGFR of <60 mL/min reported by the aMDRD formula underwent isotopic measurement of GFR (over 4 h) and had eGFR calculated using CG corrected for BSA, aMDRD and CKD-Epi formulae. Data were analysed using Bland-Altman plots and regression analysis to compare methods; bias, precision and the proportion of patients correctly stratified by stage of chronic kidney disease (CKD) were also compared according to the three estimates of GFR, using (51) Cr-EDTA GFR as the gold standard. RESULTS: A total of 139 patients were recruited (female 45%), mean age 64 years and mean serum creatinine 212 µmol/L. The mean GFR (SD) (mL/min per m(2) ) for isotopic, CG, aMDRD and CKD-Epi were 47 (28), 37 (20), 32 (17) and 33 (18) (P = 0.001). CG (57%) was more likely to correctly stage CKD than aMDRD (37%) or CKD-Epi (37%), and absolute bias was significantly lower using CG than either other method (P = 0.001). CONCLUSION: In this small Australian population the CG formula corrected for BSA agreed more closely with isotopic GFR and correctly staged patients with CKD more often than the aMDRD or CKD-Epi formulae. It is important that each renal Unit considers the accuracy of estimates of GFR according to their population demographics.

Microscopic hematuria in pregnancy: relevance to pregnancy outcome.

BACKGROUND: The significance of dipstick or microscopic hematuria in pregnancy is uncertain, with some studies suggesting this is associated with a greater risk for preeclampsia. We sought to determine the prevalence and clinical significance of microscopic hematuria during pregnancy. METHODS: This was a prospective case-control study in the antenatal Clinic of St George Hospital, Kogarah, Australia, a teaching hospital without tertiary referral antenatal care, with approximately 2,600 deliveries per year. One thousand pregnant women attending for routine antenatal care were invited to have a routine urinalysis performed and be referred to a nephrology clinic for further investigation if dipstick microscopic hematuria was detected on more than 1 occasion before 32 weeks' gestation. Main outcome measures were the prevalence of dipstick hematuria, prevalence of hematuria confirmed by urine microscopy, and the development of preeclampsia or gestational hypertension or delivery of a small-for-gestational-age baby. RESULTS: One hundred seventy-eight of 902 women (20%) who entered the study had dipstick hematuria on at least 2 occasions in pregnancy; 66 of 126 women (53%) who had hematuria before 32 weeks attended the nephrology clinic, where microscopic hematuria was confirmed in 40 women (61%). Renal imaging results were normal in all except 1 woman, and all women had a serum creatinine level of 0.90 mg/dL or less (< or =80 micromol/L). The development of preeclampsia or gestational hypertension or delivery of a small-for-gestational-age baby were similar in women with and without dipstick hematuria. Microscopic hematuria persisted in half (15 women) of those who attended for follow-up after 3 months postpartum. CONCLUSION: Dipstick hematuria is very common during pregnancy, but rarely signifies a disorder likely to impact on the pregnancy outcome. Postpartum follow-up is recommended to detect women who have persistent hematuria and presumed underlying mild glomerulonephritis.

Comparisons of auscultatory hybrid and automated sphygmomanometers with mercury sphygmomanometry in hypertensive and normotensive pregnant women: parallel validation studies.

OBJECTIVE: To find a suitable replacement for mercury sphygmomanometry to measure blood pressure (BP) accurately in normal and hypertensive pregnancy. METHODS: Two parallel validation studies were carried out in 340 pregnant women, 170 with a hypertensive disorder and 170 normotensive women. An auscultatory hybrid sphygmomanometer, A&D UM-101, and a professional automated oscillometric device for office and clinic use, Omron HEM-907, were tested. Using a modified British Hypertension Society (BHS) Protocol, nine sequential BP recordings were taken alternating between the mercury sphygmomanometer and the study device. The first readings for each device were discarded, and three differences between mercury and study device were calculated for each woman for SBP and DBP. Main outcome measures were the percentages of BP readings that were within 5, 10 and 15 mmHg absolute difference from mercury sphygmomanometry. RESULTS: Women in both studies were an average of 34 weeks' gestation and of similar ethnicity, age and BMI. In hypertensive women, 29% had preeclampsia and 73% were receiving antihypertensives. Amongst hypertensive women, SBP was within 5 mmHg of mercury BP in 94% of readings with the auscultatory device and 75% with the automated device (P = 0.021); DBP was within 5 mmHg in 97 and 61% readings, respectively (P = 0.001). Results were similar amongst normotensive pregnant women. Both devices achieved an A/A rating according to the BHS protocol. CONCLUSION: The auscultatory hybrid sphygmomanometer is more accurate than the automated oscillometric device in pregnancy, specifically in hypertensive pregnancies. It is an acceptable replacement for mercury sphygmomanometry in pregnancy.

The nitric oxide system in glucocorticoid-induced hypertension.

The blood pressure-raising effects of adrenocortical steroids with predominantly glucocorticoid activity, both naturally occurring and synthetic, are well known. Recent evidence suggests that the nitric oxide system plays a key role in the hypertension produced by glucocorticoids. Glucocorticoid actions at various sites in the nitric oxide synthase (NOS) pathway may result in elevated blood pressure. These include: alterations in l-arginine availability or transport; NOS2 and NOS3 downregulation; reduced cofactor bioavailability; NOS uncoupling; a concomitant elevation in reactive oxygen species and removal of nitric oxide (NO) from the vascular environment; alterations in whole body antioxidant status; and erythropoietin induced resistance to NO.

Markers of cardiovascular disease risk after hypertension in pregnancy.

OBJECTIVES: Women with a history of preeclampsia or gestational hypertension have an increased risk of cardiovascular disease. Underlying cardiovascular risk factors, persistent endothelial dysfunction or sympathetic overactivity may contribute to this risk. We studied markers of cardiovascular disease risk in nonpregnant women with a history of hypertension in pregnancy. METHODS: Women with a history of preeclampsia (n = 39), gestational hypertension (n = 27) and normal pregnancies (n = 35) were studied 2-12 years after delivery. Laboratory measures included plasma fasting lipids, glucose, insulin, creatinine and urinary albumin-to-creatinine ratio. Blood pressure was measured by 24-h ambulatory blood pressure monitoring, endothelial function by flow-mediated dilatation and sympathetic activity by both head-up tilt test and cold pressor test, including the response of the circulating renin-angiotensin system to tilt testing. RESULTS: Compared with women who had previous normal pregnancies, women with a history of preeclampsia or gestational hypertension have higher ambulatory blood pressure, BMI and relative insulin resistance. Glomerular filtration rate, albumin-to-creatinine ratio, endothelial function and sympathetic activity was similar among the three groups. CONCLUSION: Women with a history of preeclampsia or gestational hypertension have features of the metabolic syndrome which are presumably present already before pregnancy, predisposing them to hypertensive disorders of pregnancy and later cardiovascular risk. In this study, we found no evidence for early renal damage, endothelial dysfunction or sympathetic overactivity in the postpartum state.

Transient gestational hypertension: Not always a benign event.

OBJECTIVE: Pregnancy outcome in women with transient gestational hypertension (TGH);defined as de novo blood pressure elevation after 20weeks gestation that normalizes by subsequent evaluation in a Day Assessment Unit. STUDY DESIGN: Retrospective cohort analysis of hypertensive pregnancies between 2003 and 2008. MAIN OUTCOME MEASURES: Final hypertensive delivery diagnosis and composites of adverse maternal and fetal outcome. RESULTS: Overall 1417 women were referred; 890 met criteria; 41% (65% of study population) had TGH. Twenty percent with TGH developed gestational hypertension and 19% preeclampsia. Women with TGH who developed preeclampsia had similar composite adverse maternal outcomes to other preeclamptic women (51% vs. 63%; p=0.24) but fewer adverse fetal outcomes (50% vs. 71%; p<0.01) due to less prematurity (30% vs. 45%; p=0.02) and small for gestational age babies (33% vs. 51%; p=0.02). Within the TGH population;developing gestational hypertension or preeclampsia was associated with referral at gestation <33weeks (RRR 2.8; p<0.01);initial average systolic blood pressure 130-139mmHg (RRR 2.1; p<0.01) and initial average diastolic blood pressure 80-89mmHg (RRR 3.2; p<0.01). CONCLUSION: TGH after 20weeks is common in pregnancy. Although initial assessment implies low risk;the risk of progression to gestational hypertension or preeclampsia is substantial and warrants appropriate clinical surveillance.

Blood pressure measurement in pregnancy: the effect of arm circumference and sphygmomanometer cuff size.

This study aimed to assess the difference in blood pressure readings between the standard and large cuff and to determine if such a difference applies over a range of arm circumferences (ACs) in pregnancy. We measured blood pressure on 219 antenatal women. Six blood pressure readings were taken, three with a standard 'adult' and three with a 'large' cuff, in random order. A random zero sphygmomanometer was used by a trained observer. Women with an AC >33 cm were similar in age, gestational age and parity but were heavier and had more hypertension than those with AC ≤33 cm. There was a systematic difference between the standard and large cuff of 5-7 mmHg with little effect due to AC. We were unable to demonstrate an association between the standard and large cuff blood pressure difference and increasing blood pressure. Our study has shown that both systolic and diastolic blood pressure measurements are more dependent on the cuff size used than AC and for the individual it is difficult to predict the magnitude of effect the different cuff sizes will have on blood pressure measurements. This study has shown the presence of an average difference in blood pressure measurement between standard and large cuffs in pregnancy, and does not support the arbitrary 33 cm 'cut-off' recommended in guidelines for the use of a large cuff in pregnancy.

Measuring protein excretion in pregnancy.

The recognition and detection of proteinuria has been acknowledged as an important clinical marker of renal disease since 1827 when Richard Bright published his landmark medical case reports. In more recent times, the broader community of clinicians has come to share the enthusiasm of nephrologists in recognizing the importance of protein excretion, not only as a marker of current renal disease but also as a predictor of long-term renal and cardiovascular morbidity and mortality. It is important that methods for detecting and measuring proteinuria are accurate, and this is particularly relevant to diseases that are defined by the detection of proteinuria, such as pre-eclampsia. This review will first discuss current knowledge of protein handling by the normal kidney, then the changes in normal and hypertensive pregnancy, and finally, how recent advances in our understanding of proteinuria may affect our future management of hypertensive pregnancies.

Darbepoetin alfa administered monthly maintains haemoglobin concentrations in patients with chronic kidney disease not receiving dialysis: a multicentre, open-label, Australian study.

AIM: Darbepoetin alfa, an erythropoiesis-stimulating protein, has a longer serum half-life than recombinant human erythropoietin, allowing less-frequent administration. This study aimed to demonstrate that once-monthly (QM) darbepoetin alfa administration would maintain haemoglobin (Hb) concentrations in subjects with chronic kidney disease (CKD) not receiving dialysis who had previously been administered darbepoetin alfa every 2 weeks (Q2W). METHODS: This was a multicentre study in which subjects with CKD receiving stable Q2W darbepoetin alfa doses and with stable Hb (100-130 g/L) were started on QM darbepoetin alfa dosing. The initial QM darbepoetin alfa dose was equivalent to the cumulative darbepoetin alfa dose administered during the month preceding enrollment. Darbepoetin alfa doses were titrated to maintain Hb concentrations between 100 and 130 g/L. The primary endpoint was the proportion of subjects maintaining mean Hb >or= 100 g/L during the evaluation period (weeks 21-33). RESULTS: Sixty-six subjects were enrolled in the study and all received at least one dose of darbepoetin alfa; 55 (83%) had mean Hb >or= 100 g/L during evaluation. Mean (SD) Hb concentrations at baseline and during the evaluation period were 119 (8.7) g/L and 114 (9.8) g/L, respectively. The median QM darbepoetin alfa dose at baseline and during the evaluation period was 80 microg. Darbepoetin alfa was considered to be well-tolerated. CONCLUSION: Patients with CKD not receiving dialysis who are receiving darbepoetin alfa Q2W can be safely and effectively extended to darbepoetin alfa QM. Dosing QM may simplify anaemia management for patients and health-care providers.

Effect of synthetic corticosteroids on vascular reactivity in the human forearm.

Exogenous cortisol raises blood pressure (BP) and suppresses acetylcholine (ACh)-induced vasodilatation in healthy male volunteers. This study tests the hypothesis that the activation of either classical type I or II corticosteroid receptors by synthetic corticosteroids induces endothelial dysfunction. In two separate studies, dexamethasone or fludrocortisone was administered to healthy male subjects over five days. BP, metabolic parameters, and forearm blood flow (FBF) responses to intra-arterial ACh and nitroprusside (SNP) were measured on day 5 of treatment. Fludrocortisone (800 microg/day) and dexamethasone (3 mg/day) increased BP from control measurements, but not when compared with placebo. Metabolic effects of the steroids were consistent with their known actions. Endothelium-dependent vasodilatation was enhanced by fludrocortisone, most obviously in the presence of nitric oxide (NO) synthase inhibition with NG-mono-methyl-L-arginine (LNMMA). Dexamethasone did not suppress endothelium dependent or independent vasodilatation. Non-NO-mediated endothelium-dependent vasodilatation was increased by systemic mineralocorticoid excess but unaffected by glucocorticoid excess. These results do not support the notion that cortisol-induced vascular effects are mediated through classical corticosteroid receptors.

Acute effects of hydrocortisone on plasma nitrate/nitrite activity and forearm vasodilator responsiveness in normal human subjects.

1. The aim of the present study was to examine the acute effects of cortisol infusion on plasma nitrate/nitrite (NO) activity and forearm vascular responsiveness to acetylcholine. 2. We performed two randomized, placebo-controlled, cross-over studies. Study A examined the effects of intravenous hydrocortisone (200 mg over a 3 h period) on blood pressure (BP) and plasma NO activity in six healthy male volunteers. Study B examined the effects of intra-arterial hydrocortisone on cholinergic vasodilator responsiveness in six healthy male volunteers. Vasodilator responsiveness was measured by bilateral strain gauge plethysmography. 3. In study A, there was no significant change in BP during the hydrocortisone infusion. Comparing values obtained following 180 min infusion of hydrocortisone and control, there were significant increases in plasma cortisol (3441 +/- 342 vs 209 +/- 29 nmol/L, respectively; P < 0.001) and glucose (5.7 +/- 0.2 vs 4.6 +/- 0.2 mmol/L, respectively; P < 0.05) and a reduction in plasma renin concentration (PRC) (8.1 +/- 1.2 vs 11.0 +/- 1.8 pg/mL, respectively; P < 0.05) following hydrocortisone infusion. However, there were no significant changes in either plasma NO or in the endogenous NO synthase inhibitors asymmetrical and symmetrical dimethylarginine. 4. In study B, there was no significant change in BP or in cholinergic vasodilator responsiveness during the hydrocortisone infusion. 5. Short-term cortisol infusions do not alter biochemical or physiological markers of NO activity. If cortisol-induced hypertension is mediated by suppression of NO activity in humans, it seems likely that these changes take more than 3 h to become detectable.

Glucocorticoids and the kidney.

Glucocorticoids are widely used by nephrologists for their immunomodulatory and anti-inflammatory effects. The present review considers three aspects of glucocorticoids with which nephrologists may be less familiar: (i) renal metabolism; (ii) effects on renal haemodynamics; and (iii) effects on blood pressure as they relate to the kidney.