Significant Change In Glomerular Filtration Rate Research Articles

The Cardiorenal Effects of Chronic Phosphodiesterase-V Inhibition in Preclinical Diastolic Dysfunction (Stage B Heart Failure)

ObjectiveTo determine whether chronic phosphodiesterase-V (PDEV) inhibition with tadalafil will improve urinary sodium excretion, glomerular filtration rate (GFR), plasma cyclic guanosine 3’, 5’-monophosphate (cGMP), and urinary cGMP excretion in response to volume expansion (VE) in patients with preclinical diastolic dysfunction (PDD) or stage B heart failure. BackgroundPDD is defined as abnormal diastolic function with normal systolic function, without clinical heart failure. PDD is predictive of development of heart failure and all-cause mortality. Impaired renal function and attenuated cGMP response to VE are hallmarks of PDD. MethodsA double-blind, placebo-controlled, proof-of-concept study was conducted to compare 12 weeks of tadalafil 20 mg daily (n = 14) vs placebo (n = 7). Subjects underwent 2 study visits 12 weeks apart. Renal, neurohormonal and echocardiographic assessments were performed before and after intravascular VE (normal saline 0.25 mL/kg/min for 1 hour). ResultsBaseline characteristics were similar. There was no increase in GFR, plasma cGMP or urinary cGMP excretion in response to VE in either group at visit 1. At visit 2, tadalafil did not result in significant change in GFR but increased plasma cGMP and urinary cGMP excretion at baseline. In response to VE, tadalafil resulted in increased urine flow, urinary sodium excretion, GFR (7.00 [-1.0, 26.3] vs -9.00 [-24.5, 2.0] mL/min/1.73m2; P = 0.02) and plasma cGMP (0.50 [-0.1, 0.7] vs -0.25 [-0.6, -0.1] pmol/mL; P = 0.02). It did not improve urinary cGMP excretion after VE. ConclusionIn PDD, chronic PDEV inhibition with tadalafil improved renal response to VE through increased urine flow, urinary sodium excretion, GFR, and plasma cGMP. Further studies are required to determine whether this enhanced renal response can mitigate progression to clinical heart failure.

Effects of milrinone on renal perfusion, filtration and oxygenation in patients with acute heart failure and low cardiac output early after cardiac surgery

PurposeEarly postoperative heart failure is common after cardiac surgery, and inotrope treatment may impact renal perfusion and oxygenation. We aimed to study the renal effects of the inodilator milrinone when used for the treatment of heart failure after weaning from cardiopulmonary bypass (CPB). Material and methodsIn 26 patients undergoing cardiac surgery with CPB, we used renal vein catheterization to prospectively measure renal blood flow (RBF), glomerular filtration rate (GFR), and renal oxygenation. Patients who developed acute heart failure and low cardiac output (cardiac index <2.1 L/min/m2) at 30 min after weaning from CPB (n = 7) were given milrinone, and the remaining patients (n = 19) served as controls. Additional measurements were made at 60 min after CPB. ResultsIn patients with acute postoperative heart failure, before receiving milrinone, renal blood flow was lower (−33%, p < .05) while renal oxygen extraction was higher (41%, p < .05) compared to the control group. Milrinone increased cardiac index (21%, p < .001), RBF (36%, p < .01) and renal oxygen delivery (35%, p < .01), with no significant change in GFR and oxygen consumption compared to the control group. ConclusionsIn patients with acute heart failure after weaning from CPB, the milrinone-induced increase in cardiac output was accompanied by improved renal oxygenation. Trial registrationClinicalTrials.gov; identifier NCT02405195, date of registration; March 27, 2015, and NCT02549066, date of registration; 9 September 2015.

Arteriolar Hyalinosis Predicts Increase in Albuminuria and GFR Decline in Normo- and Microalbuminuric Japanese Patients With Type 2 Diabetes

This study investigated the association between renal histology, as assessed by morphometric analysis using light (LM) and electron (EM) microscopy, and changes in urinary albumin excretion (UAE) and glomerular filtration rate (GFR) in Japanese people with type 2 diabetes in the early stages of diabetic nephropathy. We performed percutaneous renal biopsies in 29 patients with type 2 diabetes (22 men, mean ± SD age 49 ± 10 years and GFR 119 ± 27 mL/min/1.73 m2, with 15 normoalbuminuric [UAE <20 μg/min] and 14 microalbuminuric [UAE 20-200 μg/min]) to clarify which histological factors were associated with changes in UAE and GFR during 8.0 ± 3.5 years' follow-up. Glomerular structural changes including mesangial volume fraction [Vv(Mes/glom)] were estimated using EM, whereas the index of arteriolar hyalinosis (IAH) score was assessed by LM. Patients underwent annual measurement of GFR using iohexol injection with simultaneous urine collections for UAE. Vv(Mes/glom) was negatively correlated with baseline and follow-up GFR but not with UAE. The IAH score was positively correlated with UAE and negatively correlated with GFR at follow-up, but it was not correlated with either UAE or GFR at baseline. GFR at follow-up was significantly decreased from baseline in patients with IAH scores ≥2.0 and significantly lower than in patients with IAH scores <2.0. Patients with IAH scores <2.0 showed no significant change in GFR during follow-up. Arteriolar hyalinosis is an additional histological predictor for albuminuria increase and GFR decline in normo- and microalbuminuric Japanese people with type 2 diabetes.

Rapid blood clearance and lack of long-term renal toxicity of 177Lu-DOTATATE enables shortening of renoprotective amino acid infusion

The aim of the study was to investigate the feasibility of shortening the recommended 4-h renoprotective amino acid infusion in patients receiving peptide receptor chemoradionuclide therapy (PRCRT) using radiosensitizing 5-fluorouracil. We evaluated the clearance of radiopeptide from the blood, long-term nephrotoxicity in patients undergoing PRCRT with the conventional 4-h amino acid infusion and renal uptake in patients receiving an abbreviated infusion. The whole-blood clearance of (177)Lu-DOTA-octreotate (LuTate) was measured in 13 patients receiving PRCRT. A retrospective analysis of short-term and long-term changes in glomerular filtration rate (GFR) in 96 consecutive patients receiving a 4-h infusion was performed. Renal LuTate retention estimated using quantitative SPECT/CT in 22 cycles delivered with a 2.5-h amino acid infusion was compared with that in 72 cycles with the 4-h infusion. LuTate demonstrated biexponential blood clearance with an initial clearance half-time of 21 min. Approximately 88 % of blood activity was cleared within 2 h. With the 4-h protocol, there was no significant change in GFR (1.2 ml/min mean increase from baseline; 95 % CI -6.9 to 4.4 ml/min) and no grade 3 or 4 nephrotoxicity at the end of induction PRCRT. The long-term decline in GFR after a median follow up of 22 months was 2.2 ml/min per year. There was no significant difference in the renal LuTate retention measured in patients receiving a 2.5-h amino acid infusion compared to those who had a 4-h infusion. The greatest renal exposure to circulating radiopeptide occurs in the first 1 - 2 h after injection. This, combined with the safety of LuTate PRCRT, allows consideration of an abbreviated amino acid infusion, increasing patient convenience and reducing human resource allocation.

Estimating Renal Function in Morbidly Obese Patients

This paper aims to evaluate, in a clinical context, current creatinine-based formulas commonly used to calculate renal function in morbidly obese patients. A retrospective analysis was performed of the estimates of renal function of 63 obese or morbidly obese patients undergoing gastric bypass surgery. Each patient's glomerular filtration rate (GFR) was calculated using five methods, both before and after surgery, and these approximations were then compared. Prior to surgery, the values offered by the five formulas for the renal function of this population ranged widely, by over a factor of 2. After surgery, the three weight-based GFR estimation methods indicated that a significant change in GFR had occurred, but the two non-weight-based formulas showed no significant change in estimated GFR. At baseline and after significant weight loss, creatinine-based formulas differ twofold in their estimates of renal function of the morbidly obese. An accurate method for calculating these patients' renal function is required to improve patient safety with drug dosing as well as to ensure early detection of renal failure.

1685 PERCUTANEOUS NEEDLE STICK ACCESS INTO THE KIDNEY IS ASSOCIATED WITH VASOCONSTRICTION

You have accessJournal of UrologyStone Disease: New Technology/SWL, Ureteroscopic or Percutaneous Stone Removal1 Apr 20111685 PERCUTANEOUS NEEDLE STICK ACCESS INTO THE KIDNEY IS ASSOCIATED WITH VASOCONSTRICTION Rajash Handa, Cynthia Johnson, Ehud Gnessin, Bret Connors, Andrew Evan, and James Lingeman Rajash HandaRajash Handa Indianapolis, IN More articles by this author , Cynthia JohnsonCynthia Johnson Indianapolis, IN More articles by this author , Ehud GnessinEhud Gnessin Indianapolis, IN More articles by this author , Bret ConnorsBret Connors Indianapolis, IN More articles by this author , Andrew EvanAndrew Evan Indianapolis, IN More articles by this author , and James LingemanJames Lingeman Indianapolis, IN More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2011.02.1862AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The percutaneous nephrolithotomy (PCNL) procedure for removing stones from the kidney involves gaining access to the collecting system by advancing a 18-gauge needle through the skin and kidney until the needle tip enters the urinary collecting system, and then the needle access tract is expanded and stabilized so that a channel is created for the introduction of endoscopic instrumentation to remove stones. We have shown in animal models that percutaneous access procedures can acutely impair renal function, resulting in marked reductions in glomerular filtration rate (GFR) and renal plasma flow (RPF) of 50–60% (J Endourology 20:1030–40, 2006). The surgical factors contributing to the PCNL-associated reduction in renal function are unknown. Therefore, the focus of the present study was to determine if insertion of the 18-gauge needle through the skin and into the kidney initiates the decrease in renal function observed immediately after PCNL. METHODS Acute experiments were performed in seven anesthetized adult female farm pigs. GFR and RPF were assessed by the renal clearance of inulin and para-aminohippuric acid, respectively, before and immediately after needle stick access. RESULTS A single needle stick to access the pig's urinary collecting system caused significant falls in GFR and RPF of ≈22% and ≈32%, respectively, in the treated kidney. The fall in renal function was not limited to the needle-treated kidney but also occurred in the opposite untreated kidney, albeit to a lesser extent (see figure). Our previously published work has shown that there is no significant change in GFR and RPF in either kidney of sham-treated pigs (J Endourology 20:1030–40, 2006). CONCLUSIONS The simple insertion of a needle into one kidney for percutaneous access to the urinary collecting space has significant effects on bilateral renal function. This highlights that the kidney is highly sensitive to the trauma induced by needle insertion and responds with vasoconstriction in both kidneys&em;an effect that was previously not known. © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 4SApril 2011Page: e677-e678 Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.MetricsAuthor Information Rajash Handa Indianapolis, IN More articles by this author Cynthia Johnson Indianapolis, IN More articles by this author Ehud Gnessin Indianapolis, IN More articles by this author Bret Connors Indianapolis, IN More articles by this author Andrew Evan Indianapolis, IN More articles by this author James Lingeman Indianapolis, IN More articles by this author Expand All Advertisement Advertisement PDF DownloadLoading ...

Effect of Angiotensin II Type 1 receptor blocker, Candesartan, and β1adrenoceptor blocker, Atenolol, on brain damage in ischemic stroke

This work aims at studying the possible alteration of renal renin secretion after human ischemic stroke and correlating it to the post stroke neurological and renal function alterations using angiotensin II type 1(AT1) receptor blocker (ARB), candesartan, and beta 1 adrenoreceptor blocker atenolol, which inhibits renin secretion, in Wistar rats subjected to middle cerebral artery occlusion. Methods . This study comprised 21 patients with cerebral ischemic stroke. Seventeen normal persons were used for comparison. Recumbent and standing plasma renin activity (PRA), reflex plasma renin sensitivity, plasminogen activator inhibitor and creatinine clearance (Ccr) were estimated at admission and two weeks later. Moreover, 60 male Wistar rats were divided into two groups SHAM and ischemic. Each of the two groups was further subdivided into three subgroups, non-treated, atenolol treated, and candesartan treated. In all rats, mean arterial blood pressure (MAP), systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse pressure (PP), heart rate (HR), neurobehavioral evaluation, Ccr, PRA, and infarct size were measured. Results . Together with the significant deterioration of the neurological score, focal cerebral ischemia in rats resulted in increased PRA and decreased glomerular filtration rate (GFR). In ischemic stroke patients, GFR was significantly decreased at admission and two weeks later, PRA increased at admission and two weeks later while plasma renin reflex secretion sensitivity had decreased significantly at admission relative to controls, but it increased significantly 2 weeks later. Atenolol caused significant improvement of the neurobehavioral score and renal function and decrease infarct size of rats subjected to focal cerebral ischemia whereas candesartan caused significant improvement of the neurobehavioral score and decreased infarct size with no significant change in GFR. Neither atenolol nor candesartan caused significant change in MAP, SBP, DBP, PP and HR Conclusion . (1) Ischemic stroke seems to be associated with a postischemic increase of the plasma renin secretion, which may increase the infarct size in the brain and may induce acute renal insufficiency. (2) This study confirms that Atenolol and ARBs could benefit ischemic stroke patients without altering blood pressure.

Temporal relation between body mass index and renal function in individuals with hypertension and excess body weight

Objective Recent evidence has suggested obesity as an independent risk factor for chronic kidney disease. However, the temporal relation between body mass index (BMI) and early renal dysfunction is unknown. This study aimed at evaluating whether longitudinal variations in BMI would reflect on changes in estimated glomerular filtration rate (GFR) in hypertensive individuals with excess body weight. Methods This was a cross-sectional, longitudinal study. Results Of the 218 participants who attended the first examination, 150 were available for paired final analyses. At the end of follow-up, GFR decreased by 1.024 mL/min for each 1-kg/m 2 increment in BMI ( P < 0.03). When BMI was analyzed in quartiles, a positive graded relation with GFR changes was observed in quartiles 1 and 2 (individuals who maintained or lost weight), and a negative relation in quartiles 3 and 4 (individuals who gained weight, P = 0.05). A significant difference was observed between the smallest and highest BMI quartiles ( P = 0.01). At the end of follow-up, the 76 participants (51%) who gained weight (+4.6 ± 0.4 kg) showed a reduction in GFR (−2.99 ± 1.99 mL/min) of borderline significance ( P = 0.06) and a significant increase in fasting plasma glucose and triacylglycerol levels. Conversely, the 74 participants who maintained or lost weight showed no significant change in GFR and in fasting plasma glucose and triacylglycerol levels, although their blood pressure decreased significantly. Conclusions Our study showed a significant temporal association between changes in BMI and GFR in overweight and obese hypertensive patients.

Hemodynamic effect of angiotensin II receptor blockade in postmenopausal women on a high-sodium diet: A double-blind, randomized, placebo-controlled study

Background: Hypertension becomes increasingly prevalent after menopause. Postmenopausal women are more responsive to salt than premenopausal women, and they have been reported to develop marked renal vasoconstriction on a high-sodium diet. Objective: The aim of this study was to assess whether angiotensin II receptor blockade can restore a normal pattern of renal response to salt in postmenopausal women on a high-sodium diet. We also assessed segmental renal sodium handling in that population. Methods: Normotensive and hypertensive postmenopausal women not receiving hormone replacement therapy were enrolled in this prospective, double-blind, placebo-controlled, crossover study. They were assigned to receive irbesartan 150 mg or placebo for 6 weeks; the sequence in which they received irbesartan or placebo was randomized. During the last week of treatment, they received a high-sodium diet (250 mmol/d). Ambulatory blood pressure (ABP), glomerular filtration rate (GFR), and effective renal plasma flow (ERPF) were measured using sinistrin and para-amino-hippurate clearances. Renal sodium handling was assessed by measuring endogenous lithium clearance on day 7 of the high-salt diet. Results: Nineteen women (mean age, 54.7 years; range, 43–72 years; 7 normotensive subjects [mean age, 53.4 years; range, 47–61 years] and 12 hypertensive subjects [mean age, 55.4 years; range, 43–72 years]) were included in the study. When the data for all 19 subjects were pooled, ABP was significantly lower with irbesartan than placebo both during the day (120 [3]/79 [2] vs 127 [3]/85 [2] mm Hg; both, P < 0.01) and at night (systolic BP, 107 [4] vs 111 [4] mm Hg [ P < 0.01] and diastolic BP, 71 [2] vs 75 [2] mm Hg [ P < 0.05]). Compared with placebo, irbesartan was not associated with a significant change in GFR in either the normotensive or the hypertensive women. When the data for all 19 subjects were pooled, irbesartan was associated with a significant increase in ERPF compared with placebo (372 [21] vs324 [18] mL/min · 1.73 m 2; P < 0.05). When the hypertensive and normotensive women were considered separately, the effect was more pronounced in the hypertensive women than in the normotensive women, but the changes did not reach statistical significance. When the data for all subjects were pooled, irbesartan was associated with a significant increase in daytime urinary sodium excretion compared with placebo (135 [13] vs 106 [13] μmol/min; P < 0.05) and a significant decrease at night (109 [13] vs 136 [19] μmol/min; P < 0.05). Fractional excretion of lithium (FELi), an inverse marker of proximal sodium reabsorption, increased significantly during the daytime with irbesartan compared with placebo (47% [6.5%] vs 35% [4.7%]; P < 0.05). At nighttime, FELi was significantly higher in the hypertensive subjects receiving irbesartan compared with placebo (43% [7.2%] vs 29% [6.5%]; P < 0.05). The fractional distal reabsorption of sodium did not change significantly with irbesartan compared with placebo. Conclusions: The results from this study suggest that angiotensin II receptor blockade had a favorable impact on BP, renal hemodynamics, and renal sodium handling in these salt-replete postmenopausal women. Blockade of the renin-angiotensin system restored the normal pattern of renal response to high sodium intake in these women.

Anti-albuminuric effect of losartan versus amlodipine in hypertensive Japanese patients with type 2 diabetes mellitus: A prospective, open-label, randomized, comparative study

Abstract. The antiproteinuric effect of the angiotensin II receptor-antagonist losartan has been observed in patients with type 2 diabetes mellitus (T2DM). Proteinuria is considered to be a predictor of the progression of kidney disease. The aims of the present study were to compare and examine the ability of losartan and amlodipine to ameliorate albuminuria in hypertensive Japanese patients (systolic blood pressure ≥140 mm Hg or diastolic blood pressure ≥90 mm Hg) with T2DM and whether the change in albuminuria was associated with a change in glomerular filtration rate (GFR). This prospective, open-label, randomized, comparative study was conducted over 3 months at the Kinki University School of Medicine, Osaka-Sayama, Japan. Hypertensive patients with T2DM were enrolled and randomly assigned to 1 of 2 study groups receiving either losartan (25-100 mg/d) or the calcium channel-blocker amlodipine (2.5-5 mg/d). Urinary albumin excretion (UAE), creatinine clearance, and GFR were recorded at study initiation (baseline) and study end (month 3). The GFR was measured from the fractional renal accumulation of (99m)Tc-diethylenetriaminepentaacetic acid. Adverse events (AEs) were monitored by a clinical research nurse during the examination. Fifty patients were asked to enroll and 38 returned the informed written consent. Thirty-five Japanese patients were included in the final study analysis. Seventeen patients were assigned to the losartan group (male sex, 10 [58.8%]; mean [SD] age, 58.1 [8.2] years) and 18 were assigned to the amlodipine group (male sex, 10 [55.6%]; mean [SD] age, 57.4 [8.9] years); no significant between-group difference in demographics was observed. A significant decrease from baseline to month 3 of mean (SD) UAE was observed in the losartan group (352.5 [556.6] mg/d vs 275.7 [466.1] mg/d; P = 0.048). No significant difference in mean (SD) UAE was observed in the amlodipine group for the same time period (298.2 [416.6] mg/d vs 322.7 [415.4] mg/d). There was a statistically significant difference found in the mean (SD) percent change of UAE from baseline to month 3 in the losartan group compared with the amlodipine group (-23.52 [28.42] vs +27.90 [63.51]; P = 0.004). Neither group was associated with a significant change in GFR during the course of the study. No patient discontinued the study due to AEs that were considered, by the investigator, to be possibly or probably associated with study treatment. Treatment with losartan, but not amlodipine, was associated with a reduction in albuminuria in these hypertensive Japanese patients with T2DM within a period as short as 3 months. Neither drug was associated with a significant change in GFR. Therefore, the reduction of UAE was independent of a change in the GFR.

The effect of statins on urinary albumin excretion and glomerular filtration rate: results from both a randomized clinical trial and an observational cohort study

Statins improve cardiovascular outcome, but less is known on the renal outcome. We, therefore, studied the relationship between the use of statins and urinary albumin excretion (UAE) and glomerular filtration rate (GFR) in two settings: a randomized controlled trial (RCT) and an observational cohort study, in which patients were included to study the impact of an elevated UAE on renal and cardiovascular prognosis. We used data from the Prevention of REnal and Vascular ENd-stage Disease Intervention trial (PREVEND-IT) and the PREVEND cohort study. The PREVEND-IT subjects (788 with a UAE 15-300 mg/day) received pravastatin 40 mg/day vs placebo and/or fosinopril 20 mg/day vs placebo in a 2x2 factorial-RCT design. Of the 3440 cohort subjects, 469 used statins during the 4-year follow-up period. Multivariate-regression adjusted for confounding factors and the propensity score was used to estimate the relation between statin use and UAE and GFR. In the RCT, pravastatin did not change UAE or GFR, neither in fosinopril yes/no subgroups. In the observational cohort, statin use was associated with a rise in UAE (+12.1%), compared with statin non-use (+3.6%, P<0.001). This rise was most pronounced in those on statins prior to the first screening [+24.8% (95% CI: 11.9-39.2)], those using statins>3 years [+18.5% (7.3-30.8)] and those with >1 or >2 defined daily doses (+15.7 and +17.3%, respectively). These differences remained significant after adjustment for relevant variables and propensity score. The rise in UAE could not be attributed to a higher dose or a specific statin. GFR fell in 4 years in both statin users and non-users (4.6+/-13.5 and 2.4+/-11.2, respectively). The fall in GFR between groups was not different after adjustment (P=0.11). We conclude from the RCT data that statins do not lower UAE in subjects selected because of an elevated UAE instead of hyperlipidaemia. In the observational cohort study, the use of statins similarly was not associated with a fall in UAE; UAE instead increased. Statin treatment was not associated with a significant change in GFR in these subjects with only modestly impaired GFR.

Effect of rosuvastatin or atorvastatin on urinary albumin excretion and renal function in type 2 diabetic patients

The effect of rosuvastatin or atorvastatin on urinary albumin excretion (UAE) was determined in type 2 diabetic patients. A randomized, double-blind, parallel-group, response-based design compared rosuvastatin 10 mg (titrated to 40 mg) with atorvastatin 10 mg (titrated to 80 mg) in type 2 diabetic patients with dyslipidemia, with dose titration to an LDL-C target of <3.0 mmol/L. Overnight timed urine collections were obtained at baseline, 8 and 16 weeks to UAE. Glomerular filtration rate (GFR) was determined using the Modification of Diet in Renal Disease formula. Patients with paired, UAE collections of at least 8 h duration were analyzed ( n = 344). No significant change from baseline in UAE was observed for either treatment group or between-treatment groups at 16 weeks, and median UAE for both treatment groups remained within normal limits (rosuvastatin 4.5 μg/min, atorvastatin 5.0 μg/min). A similar absence of change from baseline was observed for 51 patients with UAE above the normal range at study entry (>20 μg/min). No significant change in GFR from baseline after 16 weeks was observed for either treatment group. These data provide reassurance that type 2 diabetic patients can be treated with higher efficacy statins without clinically meaningful effects on urinary albumin excretion.

A Randomized Controlled Trial of Late Conversion from CNI‐Based to Sirolimus‐Based Immunosuppression Following Renal Transplantation

Maintenance immunosuppression with calcineurin inhibitors (CNIs) following renal transplantation is associated with nephrotoxicity and accelerated graft loss. We aimed to assess whether conversion to sirolimus-based immunosuppression would affect the progression of renal impairment. In this single center, randomized controlled trial, 40 renal transplant recipients between 6 months and 8 years post-transplant were randomly assigned to remain on their CNI (cyclosporin or tacrolimus) or to switch to sirolimus. The primary outcome measure was change in glomerular filtration rate (GFR) measurement at 12 months. Analysis was by intention-to-treat. Of the 40 patients randomized, 2 patients never took the study drugs and were excluded, leaving 19 patients per group. There was a significant change in GFR at 12 months following conversion to sirolimus (12.9 mL/min, 95% CI 6.1-19.7; p < 0.001). Following conversion, the principal adverse events were the development of rashes (68%), particularly acne, and mouth ulcers (32%). No patient in either group experienced an acute rejection episode. In renal transplant recipients, a change in maintenance therapy from CNIs to sirolimus is associated with significant improvement in GFR at 12 months.

Randomised controlled trial of recombinant human growth hormone in prepubertal and pubertal renal transplant recipients

AIMSTo evaluate the efficacy (height velocity (HV), change in height standard deviation score (ΔHSDS)), and safety (glomerular filtration rate (GFR), incidence of rejection, and calcium and glucose metabolism) of recombinant...

RENAL FUNCTION IN PAEDIATRIC PATIENTS WITH ALPHA-1-ANTITRYPSIN DEFICIENCY(AATD) AND LIVER DAMAGE

190 Renal function was investigated in 16 paediatric patients with AATD(Pi-type ZZ) and liver involvement. Ten of them were girls. Eleven of them had had overt neonatal cholestasis while in the rest of them no such episode has been observed. The patients were followed up with physical check-ups, biochemical parameters and liver histology. According to the results an overall “liver score” was given describing the grade and natural course of the liver damage: 1) slight liver damage without progression during the follow-up; 2) moderate liver damage with advanced fibrosis but no unequivocal evidence of future need for liver transplantation (OLT) and 3) unequivocal progression to cirrhosis. Renal function was investigated as glomerular filtration rate (GFR), effective renal plasma flow (ERPF), determined by the clearance of inulin and para-amino-hyppuric acid. Fifty-three children (mean age 11.8 years, 3.5-21.5 years) without signs of renal disease, served as controls. Eight children were investigated once, the others on two or more occasions. The mean age of the 16 patients at the first renal investigation was 5.9 years (0.7-18.5). Four patients were investigated both before and after OLT. Results: groups 1 and 2 had slightly but significantly lower GFR than the controls (107 ± 6, vs. 116 ± 1, p < 0.05). Group 3 had significantly higher GFR than the controls (143 ± 24, p < 0.005). There was no significant difference in the ERPF between patients and controls. In the 8 patients who were investigated repeatedly there was no significant change in GFR from the first to the last investigation, although the 4 of them who belonged to group 3 showed a tendency to a decrease in GFR. Here again, there was no difference in ERPF. In the 4 patients in whom the investigation was performed both before and after OLT, the preoperative GFR(112 ± 8) decreased significantly to 54 ± 5 (p < 0.0005). The patients with AATD had a more marked decrease in GFR than those paediatric patients who were liver transplanted of other indications. We conclude that in paediatric patients with AATD but without severe liver damage renal function is subnormal but unchanged during follow-up in severe juvenile liver disease due to AATD a hyperfiltration was observed which might be a precursor of later renal damage in patients with AATD in whom OLT is performed renal function has to be followed carefully and nephrotoxic immunosuppresive drugs have to be administered with caution.

Prevention of hypoxemia-induced renal dysfunction by perindoprilat in the rabbit

The role of angiotensin II, a potent postglomerular vasoconstrictor, in the hypoxemiainduced renal changes is still controversial. The ability of perindoprilat, an angiotensin converting-enzyme inhibitor, to prevent the acute renal effects of hypoxemia was assessed in 22 anesthetized-ventilated rabbits. In 8 untreated rabbits, hypoxemia induced a significant drop in mean blood pressure (MBP) (−12 ± 2%), glomerular filtration rate (GFR) (−16 ± 3%) and renal blood flow (RBF) (−12 ± 3%) with a concomittant increase in renal vascular resistance (RVR) (+18 ± 5%) and urine flow rate (+33 ± 14%), and without any changes in filtration fraction (FF) (−4 ± 2%). This suggests the occurrence of glomerular vasoconstriction during the hypoxemic stress. In 7 normoxemic rabbits, intravenous perindoprilat (20 μg kg ) induced an increase in urine flow rate (+17 ± 4%) and RBF (+17 ± 4%), and a decrease in MBP (−6 ± 1%), RVR (−14 ± 3%) and FF (−11 ± 2%) without a significant change in GFR. The drop in FF and the increase in RBF suggests preferential postglomerular vasodilatation. In 7 rabbits, perindoprilat prevented the occurence of the hypoxemia-induced changes in RBF and RVR without improving MBP. FF decreased significantly (−18 ± 2%), while the drop in GFR (−7 ± 2%) was partially blunted and the increase in urine flow rate (+25 ± 9%) was confirmed. These results could be explained by the inhibition of the angiotensin-mediated efferent vasoconstriction and by the inhibition of bradykinin degradation by perindoprilat. These data confirm the ability of converting-enzyme inhibitors to prevent the renal hypoperfusion induced by acute hypoxemia.

Atrial natriuretic peptide in preeclampsia: metabolic clearance, sodium excretion and renal hemodynamics.

To further elucidate the role of atrial natriuretic peptide (ANP) in preeclampsia, its metabolic clearance (MCRANP) was determined concomitantly with its effects on sodium excretion (UNa), glomerular filtration rate (GFR), and effective renal plasma flow (ERPF). Ten untreated preeclamptic primigravidae (PET) were studied at 29-37 wk gestation and again 4 mo postpartum (PP). Basal plasma concentration of ANP was significantly increased in PET compared with PP (14.8 +/- 1.9 vs. 4.1 +/- 0.5 pmol/l, respectively; P < 0.0001). MCRANP in PET and PP was 5.0 +/- 0.8 and 4.9 +/- 0.5 l/min [not significant (NS)], respectively. In PET, infusion of ANP produced (basal vs. ANP) a natriuresis (UNa 0.14 +/- 0.02 vs. 0.28 +/- 0.04 mmol/min, P < 0.001) and an increase in GFR (97 +/- 7 vs. 106 +/- 8 ml/min, P < 0.05), with ERPF unchanged (609 +/- 24 vs. 634 +/- 29 ml/min, NS). In PP, ANP infusion also produced a natriuresis (UNa 0.20 +/- 0.02 vs. 0.25 +/- 0.02 mmol/min, P = 0.01), no significant change in GFR (109 +/- 7 vs. 102 +/- 4 ml/min), and a significant reduction in ERPF (514 +/- 22 vs. 409 +/- 18 ml/min, P < 0.0001). Analysis of variance demonstrated a greater natriuretic effect of ANP in PET compared with PP (P < 0.05), similarly a significant difference in the effect of ANP on ERPF (P < 0.01) and GFR (P < 0.05) was seen but not on filtration fraction (P = 0.35).

The effects of systemic hypoxia on renal function in the anaesthetized rat.

1. In rats anaesthetized with Saffan, renal function was monitored from the left kidney from the 5th minute of spontaneous breathing of 12% O2 for two 20 min periods and during air breathing before, between and after the hypoxic periods. Two groups of animals (I and II) were used, each group comprising two subgroups in which the left kidney was innervated or denervated, respectively; in Group II, renal perfusion pressure (RPP) was maintained during the 2nd hypoxic period by occl97uding the distal aorta. 2. In both subgroups of Group I, both hypoxic periods produced hyperventilation, arterial PO2 falling to approximately 50 mmHg. Concomitantly, mean arterial pressure (MABP) fell by similar extents (approximately 23%, from a baseline level of 140 mmHg during the 2nd hypoxic period). In the innervated subgroup, renal vascular conductance (RVC) increased, but glomerular filtration rate (GFR) fell (by 48 and 6%, respectively, during the 2nd hypoxic period), while urine flow, absolute sodium excretion (UNaV) and fractional sodium excretion (FENa) fell (by 52, 63 and 61%, respectively). Baseline urine flow, UNaV and FENa were higher in the denervated subgroup, but hypoxia produced similar percentage changes from baseline in all variables. 3. In Group II, both subgroups showed similar changes during the 1st hypoxic period as the corresponding subgroups of Group I. However, during the 2nd hypoxic period when the fall in MABP was reduced to approximately 7%, the increase in RVC persisted only in the denervated subgroup; there was no significant change in GFR, urine flow, UNaV or FENa in either subgroup. 4. These results indicate that, in the rat, moderate hypoxia produces antidiuresis and antinatriuresis that are not dependent on the renal nerves, but are dependent on the hypoxia-induced fall in MABP. The fall in renal perfusion pressure (RPP) may directly determine renal function, but reflex influences upon the kidney initiated by, for example, arterial baroreceptor unloading, may play a role. The fall in GFR and increase in RVC, which persisted after denervation or when renal perfusion was controlled, implies a local dilatatory influence acting preferentially on the efferent arterioles.

Intrarenal haemodynamic and glomerular responses to inhibition of nitric oxide formation in rabbits.

1. The renal effects of inhibiting nitric oxide (NO) formation using N-nitro-L-arginine (NOLA, 20 mg kg-1) were examined using micropuncture techniques in pentobarbitone-anaesthetized rabbits. 2. Renal vascular resistance doubled from 2.7 +/- 0.5 to 5.0 +/- 1.1 mmHg ml-1 min-1 after NOLA (P < 0.01), with similar percentage increases in both pre- (149 +/- 38%, P < 0.01) and postglomerular (158 +/- 42%, P < 0.01) resistance. 3. Glomerular capillary pressure rose from 33 +/- 1 to 40 +/- 1 mmHg after NOLA (P < 0.01) but despite this, glomerular filtration rate (GFR) and single nephron glomerular filtration rate did not significantly change. 4. Blood pressure increased 18 +/- 1 mmHg (P < 0.001) within 10 min of NOLA administration and remained near this level for the next 90 min. 5. The glomerular ultrafiltration coefficient (Kf) decreased significantly from 0.085 +/- 0.022 to 0.035 +/- 0.006 nl s-1 mmHg-1 (P < 0.05). 6. Urine flow and sodium excretion increased markedly (26 +/- 9 to 337 +/- 102 microliters min-1 and 5 +/- 2 to 342 +/- 12 mumol min-1 respectively, (P < 0.001)) and sodium fractional excretion rose from 1.0 +/- 0.3 to 8.0 +/- 2.2% (P < 0.01). 7. Thus, administration of NOLA to rabbits caused vasoconstriction of both pre- and postglomerular vessels, diuresis and natriuresis without significant change in GFR, and a reduction in Kf. The results suggest that NO may play an important role in the regulation of renal haemodynamics and glomerular function.

Renal haemodynamics and tubular sodium handling following volume expansion with sodium chloride (NaCl) and glucose in healthy humans.

Renal haemodynamics estimated using inulin- and para-aminohippuric acid-(PAH) clearances and segmental tubular handling of sodium as estimated using lithium clearance where studied in fourteen healthy men. Volume expansion was induced by a 2 h (25 ml kg-1) infusion of 0.9% sodium chloride (NaCl) load. Eight of the 14 subjects were rechallenged with a 2 h infusion of 5% glucose (25 ml kg-1). In addition, ten healthy subjects were investigated with inulin and PAH-clearances during water diuresis. When NaCl was infused glomerular filtration rate (GFR) decreased from 115 to 103 ml min-1 (p < 0.002) and fractional sodium excretion increased by 85%. The fall in GFR could be due to tubuloglomerular feedback as a result of inhibition of proximal tubular sodium reabsorption. The fall in GFR raises doubt about the usefulness of NaCl as an inert control infusion in metabolic studies. During glucose infusion blood glucose rose from 4.3 to 10.9 mmol l-1 with no significant change in GFR, but fractional sodium excretion was reduced by almost 40%. The etiology of the acute antinatriuretic effect of volume expansion with glucose infusion in healthy humans is not known but a blunted decrease in plasma renin activity and erythrocyte volume fraction in conjunction with a failure to mobilize renal dopamine and an increase in plasma levels of antinatriuretic factors such as insulin and norepinephrine are all factors that may contribute to the antinatriuretic effect of a glucose infusion.