Increase In Glomerular Filtration Rate Research Articles

A mathematical model of the rat nephron: glucose transport

Mathematical models of the proximal tubule (PT), loop of Henle (LOH), and distal nephron have been combined to simulate transport by rat renal tubules. The ensemble is composed of 24,000 superficial (SF) nephrons and 12,000 juxtamedullary (JM) nephrons in 5 classes (according to LOH length); all coalesce into 7,200 connecting tubules (CNT). Medullary interstitial solute concentrations are specified. The model equations require that each nephron glomerular filtration rate (GFR) satisfies a tubuloglomerular feedback (TGF) relationship, and each initial hydrostatic pressure yields a common CNT pressure; that common CNT pressure is determined from an overall distal hydraulic resistance to flow. By virtue of the greater GFR for JM nephrons, fluid delivery to SF and JM tubules is comparable. Glucose reabsorption is restricted to the PT, cotransported with one Na in the convoluted tubule (SGLT2), and two Na in the straight tubule (SGLT1). Increasing ambient glucose from 5 to 10 mM increases proximal Na reabsorption and decreases distal delivery. This is mitigated by a TGF-mediated increase in GFR, and may thus be an etiology for TGF-mediated glomerular hyperfiltration. With SGLT2 inhibition by 95%, the model predicts that under normoglycemic conditions about 60% of filtered glucose will still be reabsorbed, so that profound glycosuria is not to be expected. Compared with glucose-driven osmotic diuresis, SGLT2 inhibition provokes greater natriuresis. When hyperglycemia is superimposed on SGLT2 inhibition, the model suggests that natriuresis may be severe, reflecting synergy of a proximal diuretic and osmotic diuresis. In sum, the model captures TGF-mediated diabetic hyperfiltration and predicts glomerular protection with SGLT2 inhibition.

Renal blood flow using arterial spin labelling MRI and calculated filtration fraction in healthy adult kidney donors Pre-nephrectomy and post-nephrectomy.

Renal plasma flow (RPF) (derived from renal blood flow, RBF) and glomerular filtration rate (GFR) allow the determination of the filtration fraction (FF), which may have a role as a non-invasive renal biomarker. This is a hypothesis-generating pilot study assessing the effect of nephrectomy on renal function in healthy kidney donors. Eight living kidney donors underwent arterial spin labelling (ASL) magnetic resonance imaging (MRI) and GFR measurement prior to and 1year after nephrectomy. Chromium-51 labelled ethylenediamine tetraacetic acid ((51)Cr-EDTA) with multi-blood sampling was undertaken and GFR calculated. The RBF and GFR obtained were used to calculate FF. All donors showed an increase in single kidney GFR of 24 - 75 %, and all but two showed an increase in FF (-7 to +52 %) after nephrectomy. The increase in RBF, and hence RPF, post-nephrectomy was not as great as the increase in GFR in seven out of eight donors. As with any pilot study, the small number of donors and their relatively narrow age range are potential limiting factors. The ability to measure RBF, and hence RPF, non-invasively, coupled with GFR measurement, allows calculation of FF, a biomarker that might provide a sensitive indicator of loss of renal reserve in potential donors. • Non-invasive MRI measured renal blood flow and calculated renal plasma flow. • Effect of nephrectomy on blood flow and filtration in donors is presented. • Calculated filtration fraction may be a useful new kidney biomarker.

Impact of kidney function on mortality after transcatheter valve implantation in patients with severe aortic valvular stenosis

AimsTranscatheter aortic valve implantation (TAVI) is an accepted alternative for patients with severe aortic valve stenosis who cannot undergo surgery. Acute kidney injury (AKI) is a serious complication in any invasive cardiovascular intervention.The objectives of the study were to determine (i) the influence of kidney function before TAVI and (ii) the impact of changes in kidney function after TAVI, including acute kidney injury (AKI), on mortality. Methods and resultsA total of 540 patients undergoing TAVI were included. Patients were divided into three groups according to glomerular filtration rate (GFR) before TAVI (A: normal renal function i.e. GFR ≥60ml/min; B: impaired renal function i.e. GFR 30–59ml/min; C: severe impaired renal function i.e. GFR <30ml/min).Multivariate analysis showed a significant impact of GFR on mortality (p<0.0008). Subgroup analysis showed significant differences between the groups in 30-day (A: 5.4%, B: 9.0%, C: 25.0%) and 12-month mortality (A: 15.0%, B: 32.0%, C: 49%). Patients who had an increase in GFR after TAVI by more than 22% (p=0.0068) had an improved survival rate, whereas a decrease in GFR by more than 15% was associated with an increased mortality rate (p=0.0051). AKI occurred in 30 patients (5.6%), of which 22 patients (73.3%) died within 12months. ConclusionOutcome is significantly related to pre-procedural kidney function. In addition, changes in kidney function after TAVI have a significant impact on mortality. Due to a very poor prognosis in patients with AKI, any effort to prevent this serious complication after TAVI needs to be taken.

Urinary TGF-1 has a supplementary value in predicting renal function recovery post unilateral ureteral obstruction.

To evaluate whether urine transforming growth factor-β1 (TGF-β1) can help identifying kidneys that would recover their function after drainage of unilateral ureteric obstructive. Forty-five patients with unilateral ureteral obstruction were included. Glomerular filtration rate (GFR) of the obstructed kidney was <10 ml/min, and all patients were treated with percutaneous nephrostomy. TGF-β1 level was measured in the urine from the obstructed kidney at the time of drainage. GFR before nephrostomy insertion and 3 months after were calculated. Patients with renal function improvement (significant increase in GFR) after nephrostomy insertion had significantly lower concentration of urine TGF-β1 (p<0.05) compared with the group that showed no change in GFR (non-functioning kidneys) The sensitivity, specificity and accuracy of urine TGF-β1 in identifying non-functioning kidney was 82, 82 and 82%, respectively. Urine TGF-β1 is a cytokine leading to renal fibrosis and has a supplementary value in differentiating, at early stage, between kidneys that would recover function after releasing unilateral ureteral obstruction from those which will not (non-functioning kidneys).

Proaterogenic metabolic disorders in patients with chronic kidney disease nondiabetic origin: possibility of statin therapy

PURPOSE AND MATERIAL: In order to study the state of coronary arteries, and dynamics of parameters of kidney function, lipid metabolism, levels of glycated hemoglobin (HbA1c), uricemia during administration of atorvastatin in a complex of standard cardioprotective treatment, we examined 54 patients with chronic kidney disease (CKD) of nondiabetic origin. All patients were divided in 2 groups: group I - 31 patients with glomerular filtration rate (GFR) <60 ml/min, who were additionally administered atorvastatin 20 mg/day; group II - 23 patients with glomerular filtration rate (GFR) more or equal 60 ml/min. On day 1 of hospitalization and after 6 months of treatment we determined levels of systolic and diastolic blood pressure (SBP and DBP), pulse pressure (PBP), lipid profile, uric acid levels, HbA1c and GFR (Cockcroft - Gault). Angiography of coronary arteries was also performed. It was found that three of four patients with CKD had coronary stenosis >50% in at least one coronary artery, combined with a substantial elevation of levels of atherogenic lipid fractions, HbA1c and uric acid. Administration of combination atorvastatin with standard treatment of CKD allowed to achieve significant reduction of levels of atherogenic lipid fractions, HbA1c, and uricemia, additional reductions in SBP and PBP by 4-5 mm Hg. Six-months therapy with statin was accompanied by 1.5 fold increase of GFR in patients with initial levels of GFR <60 ml/min. Thus, in patients with nondiabetic CKD statin therapy not only improved lipid metabolism, but also facilitated reduction of HbA1c and uricemia, improved BP control and functional ability of kidneys, especially in individuals with significant coronary artery stenosis.

OP2-12 MEASURING THE IMPACT OF MEDICAL CHRONIC KIDNEY DISEASE AND DIABETES MELLITUS ON RENAL FUNCTIONAL DECLINE FOLLOWING RADICAL NEPHRECTOMY AND NEPHRON-SPARING SURGERY FOR RENAL CELL CARCINOMA

You have accessJournal of UrologyOutstanding Posters: Benign Disease1 Apr 2014OP2-12 MEASURING THE IMPACT OF MEDICAL CHRONIC KIDNEY DISEASE AND DIABETES MELLITUS ON RENAL FUNCTIONAL DECLINE FOLLOWING RADICAL NEPHRECTOMY AND NEPHRON-SPARING SURGERY FOR RENAL CELL CARCINOMA Adiel E. Mamut, Neal E. Rowe, Philippe D. Violette, Fulan Cui, and Patrick P.W. Luke Adiel E. MamutAdiel E. Mamut More articles by this author , Neal E. RoweNeal E. Rowe More articles by this author , Philippe D. ViolettePhilippe D. Violette More articles by this author , Fulan CuiFulan Cui More articles by this author , and Patrick P.W. LukePatrick P.W. Luke More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2014.02.2562AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The risk factors for medical chronic kidney disease are well established, however, the impact of such factors in a conjunction with surgical kidney disease have been the source of recent debate. The goal of our study was to identify risk factors for renal functional decline following extirpative renal surgery, and to establish the impact of these factors on glomerular filtration rate (GFR) reduction. METHODS We present a retrospective cohort study of 344 consecutive patients who underwent surgery for a renal mass at a tertiary care center between 2002 and 2010. Patients were grouped by RN or PN and baseline characteristics were compared. Renal function was estimated by the Modification in Diet and Renal Disease (MDRD) formula. Multivariate linear regression was used to identify independent predictors of renal function. RESULTS 120 patients were treated with PN and 224 with RN. Mean age was 60.9 yr for PN and 62.6 yr for RN. Mean tumor size was 2.9cm for the PN group and 6.2cm for the RN group. Multivariate analysis identified radical nephrectomy, pre-operative GFR and Diabetes Mellitus (DM) as independent predictors of 1 year post-operative renal function. Patients undergoing RN had a mean decrease in GFR of 20.7 mL/min/1.73 m2 (95%CI 18.1- 23.3) compared to those undergoing PN. For each unit increase in pre-operative GFR, post-operative GFR increased by 0.66 mL/min/1.73 m2 (95%CI 0.60 -0.71). DM impacted a post-operative GFR decline by 3.6 mL/min/1.73 m2 (95% CI 0.7 – 6.6). CONCLUSIONS Pre-op GFR, type of surgery and DM were independent predictors of post-operative renal function. While our findings support nephron-sparing surgery for patients with chronic kidney disease, the value of nephron-sparing approaches in diabetic patients may be even greater. © 2014FiguresReferencesRelatedDetails Volume 191Issue 4SApril 2014Page: e391 Advertisement Copyright & Permissions© 2014MetricsAuthor Information Adiel E. Mamut More articles by this author Neal E. Rowe More articles by this author Philippe D. Violette More articles by this author Fulan Cui More articles by this author Patrick P.W. Luke More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Mesangioproliferative Glomerulonephritis: A 30-Year Prognosis Study

Background: Diffuse mesangioproliferative glomerulonephritis (MesP) is the most commonly diagnosed type of glomerulonephritis (GN) in Denmark, with an incidence of 10.8 million per year. In the present study, the 30-year renal survival was estimated. Methods: A retrospective cohort investigation of 140 patients with biopsy-proven MesP was performed between the period 1967-2006. Factors influencing renal survival were investigated using Cox regression analysis. Results: Renal survival at 5, 10, 20 and 30 years was 87, 78, 59 and 50%, respectively. Female survival after 30 years was significantly better than male survival (70 vs. 40%, p = 0.049). Multivariate analysis, adjusted for age, estimated glomerular filtration rate (GFR) and nephrotic syndrome (NS) was performed for each sex individually. An increase in GFR was associated with a hazard risk (HR) of 0.98 (p = 0.02) in women and 0.99 (p = 0.006) in men. Older age was associated with a HR of 1.04 (p = 0.02) in women and 1.03 (p = 0.004) in men. NS had a poorer prognosis in men (HR 2.53, p = 0.01), but not in women (HR 0.54, p = 0.38). Conclusion: Increasing age and decreasing GFR were adversely associated with renal death. Renal prognosis was better for women after 30 years, and NS resulted in a poorer prognosis in men. This suggests that disease course and prognosis are different between men and women.

Acute caloric restriction improves glomerular filtration rate in patients with morbid obesity and type 2 diabetes

AimThe role of caloric restriction in the improvement of renal function following bariatric surgery is still unclear; with some evidence showing that calorie restriction can reduce proteinuria. However, data on the impact of caloric restriction on renal function are still lacking. MethodsRenal function, as measured by glomerular filtration rate (GFR), was evaluated in 14 patients with type 2 diabetes mellitus, morbid obesity and stage 2 chronic kidney disease before and after a 7-day very low-calory diet (VLCD). ResultsAfter the VLCD, both GFR and overall glucose disposal (M value) significantly increased from 72.6±3.8mL/min/1.73m−2 BSA to 86.9±6.1mL/min/1.73m−2 BSA (P=0.026) and from 979±107μmol/min1/m2 BSA to 1205±94μmol/min1/m2 BSA (P=0.008), respectively. A significant correlation was observed between the increase in GFR and the rise in M value (r=0.625, P=0.017). ConclusionOur observation of improved renal function following acute caloric restriction before weight loss became relevant suggesting that calory restriction per se is able to affect renal function.

Effect of Insulin on ACE2 Activity and Kidney Function in the Non-Obese Diabetic Mouse

We studied the non-obese diabetic (NOD) mice model because it develops autoimmune diabetes that resembles human type 1 diabetes. In diabetic mice, urinary albumin excretion (UAE) was ten-fold increased at an “early stage” of diabetes, and twenty-fold increased at a “later stage” (21 and 40 days, respectively after diabetes diagnosis) as compared to non-obese resistant controls. In NOD Diabetic mice, glomerular enlargement, increased glomerular filtration rate (GFR) and increased blood pressure were observed in the early stage. In the late stage, NOD Diabetic mice developed mesangial expansion and reduced podocyte number. Circulating and urine ACE2 activity were markedly increased both, early and late in Diabetic mice. Insulin administration prevented albuminuria, markedly reduced GFR, blood pressure, and glomerular enlargement in the early stage; and prevented mesangial expansion and the reduced podocyte number in the late stage of diabetes. The increase in serum and urine ACE2 activity was normalized by insulin administration at the early and late stages of diabetes in Diabetic mice. We conclude that the Diabetic mice develops features of early kidney disease, including albuminuria and a marked increase in GFR. ACE2 activity is increased starting at an early stage in both serum and urine. Moreover, these alterations can be completely prevented by the chronic administration of insulin.

Estimated Glomerular Filtration Rate Changes In Patients (Pts) With Chronic Myeloid Leukemia (CML) Treated With Tyrosine Kinase Inhibitors (TKI)

IntroductionTKI are standard therapy for pts with CML. Although generally safe, they are associated with some adverse events, most of them manageable and transient. Renal dysfunction has been reported anecdotally on pts with CML treated with TKI. We investigated the incidence of acute renal failure (ARF) and chronic renal failure (CRF) among the CML pts treated with TKI, and analyzed possible relationship between treatment duration with TKI and changes in estimated glomerular filtration rate (GFR). MethodsFour hundred and seventy-five pts treated with imatinib (255 pts; 49 at 400 mg daily; 206 at 800 mg daily), dasatinib (101 pts) and nilotinib (119 pts) in prospective clinical trials at a single institution were evaluated. Pts were followed routinely with blood chemistries including renal function tests, at least weekly during the first 2-3 months, then every 2-4 weeks for 6-12 months, then every 8-12 weeks. GFR was estimated using the Modification of Diet in Renal Disease (MDRD) equation and recorded from the onset of TKI treatment until last follow up. ARF was defined as an increase in serum creatinine of ≥0.3 mg/dl, and CRF defined as an estimated GFR ≤ 60 ml/min/1.73 m2 persisting for at least 90 days. ResultsAfter a median follow-up of 50 months (range, 2 to 138 months), 19 pts (4%) developed ARF. The median time of onset for ARF was 9 days (range 4-84 days). Sixteen of 19 pts (84%) were on imatinib, 2 on nilotinib, and 1 on dasatinib (p=0.006). There was no association between imatinib dose and incidence of ARF (2% with 400mg vs 7% with 800mg) (p=0.174). The median age for pts with ARF was 58 yrs compared to 48 for pts with no ARF (p=0.009). Seventy-nine percent (15 out of 19) of ARF pts and 59% (269 of 456) of pts without ARF were male (p=0.063). During study time, estimated GFR decreased significantly in pts treated with imatinib compared to dasatinib (Figure 1) (p<0.001). Interestingly, in pts treated with nilotinib, we observed significant increase in GFR when we compare baseline GFR to the GFR in all other time points (p<0.05). 442 pts (94%) had no CRF at baseline, and 48 of these pts (11%) developed CRF over the course of TKI treatment. Among them, 39 pts (81%) were on imatinib compared to 19% on other TKIs (5 dasatinib, 4 nilotinib) (p<0.001). There was no association between imatinib dose (400mg and 800mg) and CRF incidence (p=0.591). The median age for pts who developed CRF was 61 yrs compared to 47 for those with no CRF (p=<0.001). Fifty-eight percent (28 out of 48) of CRF pts and 60 % (256 of 427) of pts without CRF were male (p=0.828). Overall CCyR rate was the same (89%) in pts who had ARF and no ARF, and overall MMR rate was 79% in pts with ARF and 83% in pts with no ARF (p=0.401). Overall CCyR rate was 98% in pts who developed CRF over the course of TKI therapy compared to 89% in pts who did not develop CKD (p=0.026). Similarly, overall MMR rate was higher (96%) in pts developed CKD compared to pts who did not have CKD (82%) (p=0.013). Overall survival and transformation free survival was not statistically different when compared pts with ARF vs no ARF and CRF vs no CRF. However, pts with ARF had decreased event free survival (EFS) when compared to no ARF pts (p=0.019). There was no EFS difference in CRF pts (0.966). [Display omitted] ConclusionLong-term treatment with imatinib may cause a significant decline in estimated GFR. Interestingly, treatment with nilotinib may cause a slight improvement in GFR. It is important that pts are monitored for renal function during therapy with TKI, with particular attention to those with risk factors for renal dysfunction. Disclosures:Ravandi:Pfizer and Novartis: Honoraria; BMS: Research Funding. Jabbour:Novartis, BMS, Ariad, and Pfizer: Consultancy. Cortes:Ariad, BMS, Novartis, Pfizer and Teva: Research Funding; BMS, Pfizer and Teva. : Consultancy.

Chronic Subcutaneous BNP Administration in Human Preclinical Systolic Dysfunction (Stage B Heart Failure) Results in Sustained Renal Responsiveness to Acute Volume Overload

Preclinical systolic dysfunction (PSD) is defined by left ventricle ejection fraction (LVEF) < 45% without symptoms of heart failure (HF) (Stage B HF). We have previously demonstrated that an impaired cardiorenal endocrine response to acute volume loading (AVL) exists in PSD and that is corrected by acute administration of subcutaneous (SQ) B-type natriuretic peptide (BNP). We hypothesized that 12 weeks of SQ BNP administration twice daily would result in a sustained enhancement of the cardiorenal response to AVL. We performed a randomized placebo-controlled double blinded proof of concept clinical trial comparing 12 weeks of SQ BNP, 10 μg/Kg bid (n=22) with Placebo (n=12), in patients with EF<45% and NYHA Class I. Each subject had 2 study visits, one at baseline and the other after 12 weeks. At each visit, echocardiogram, neurohumoral assessment and renal clearance studies with iothalmate and PAH to measure glomerular filtration rate (GFR) and renal plasma flow (RPF) were done before and after AVL (0.25 ml/kg/min of normal saline for 60 minutes).(ClinicalTrials.gov Identifier: NCT00405639) 12 weeks of SQ BNP resulted in a strong trend for a greater decrease of LV mass index from baseline as compared to placebo (-5.8±15.7 vs 2.0±5.4 g/m2 p=0.07) with a significant decrease in LV end-systolic diameter (48.1±6.7 to 46.1±7.9 mm, p< 0.05) and significant increase in LV EF (38.9±8.9 to 41.4±9.2 %, p< 0.05) only in the BNP group. In response to AVL, SQ BNP resulted in a greater increase in GFR (4.4±15 vs -9.3±15.2 ml/min/1.73m2, p< 0.05) and urinary sodium excretion (184.9±301.4 vs -18.7±95.3 mEq/min, p< 0.05) as compared to placebo. Echocardiography revealed a greater increase in LVEF (4±5 vs -0.4±3.1%, p< 0.05), with smaller end-systolic diameter (-3.2±3.7 vs -0.4±1.3 mm, p< 0.05) and E/e’ ratio (12.1±6 vs 14.8±3.4, p< 0.05) and a trend for lower RV pressure (0.1±3.1 vs 3.6±3.8 mmHg, p= 0.06) in the SQ BNP group in response to AVL with normal saline as compared to the placebo group. In PSD, 12 weeks of SQ BNP administered twice a day resulted in improved and sustained ability of the kidney to respond to intravascular volume overload with an increase in GFR and sodium excretion compared to standard of care. This enhanced renal response was associated with enhanced myocardial structure and function with no evidence of pharmacological tolerance. Further studies are warranted to determine if these physiologic observations can be translated into a delay in the progression to symptomatic HF.

M-atrial natriuretic peptide and nitroglycerin in experimental acute hypertensive heart failure: differential actions of two cGMP activating therapeutics

Background Systemic hypertension is a common characteristic in acute heart failure (HF). This increasingly common phenotype is frequently associated with renal dysfunction and requires renal enhancing therapies. In a canine model of HF and acute hypertension we defined the cardiorenal actions of M-atrial natriuretic peptide (MANP), a novel particulate guanylyl cyclase A receptor activator (pGC-A) developed at the Mayo Clinic, and nitroglycerin (NTG), a soluble guanylyl cyclase (sGC) activator. Compared to native ANP, MANP has more sustained renal enhancing, blood pressure lowering and aldosterone inhibiting action. Based on the expression of the pGC-A receptor in the glomerulus, renal tubule and adrenal gland, compared to the more widespread expression of sGC in the renal vasculature, we hypothesized that MANP would have a more robust effect upon the glomerular filtration rate (GFR) and natriuretic actions and with greater aldosterone suppressing effects than sGC activation with NTG. To test these hypotheses, we used a canine model of combined HF and hypertension. Specifically, HF was induced by chronic (10 days) rapid right ventricular pacing (180 bmp), while hypertension was induced by continuous angiotensin II infusion (on day 11). We than characterized the cardiorenal and humoral actions of intravenous MANP (n=7), NTG (n=7), and vehicle (n=7) infusion. Results Mean arterial pressure (MAP) was reduced by both MANP (139±4 to 118±3 mmHg, p<0.05) and NTG (137 ±3 to 116±4 mmHg, p<0.05); similar findings were observed for reductions in pulmonary wedge pressure with MANP (12±2 to 6±2 mmHg, p<0.05) and NTG (12±1 to 6±1 mmHg, p<0.05). MANP enhanced renal function with significant increases in GFR (38±4 to 53±5 ml/min, p<0.05), renal blood flow (132±18 to 236±23 ml/ min, p<0.05), and natriuresis (11±4 to 689±37 mEq/min, p<0.05) with inhibition of aldosterone (32±3 to 23±2 ng/ dL, p<0.05), whereas NTG had no significant effect on these renal parameters or aldosterone activation.

The synthetic triterpenoid, RTA 405, increases the glomerular filtration rate and reduces angiotensin II–induced contraction of glomerular mesangial cells

Bardoxolone methyl, a synthetic triterpenoid, improves the estimated glomerular filtration rate (GFR) in patients with chornic kidney disease and type 2 diabetes. Since the contractile activity of mesangial cells may influence glomerular filtration, we evaluated the effect of the synthetic triterpenoid RTA405 with structural similarity to bardoxolone methyl, on GFR in rats and on mesangial cell contractility in freshly isolated glomeruli. In rats, RTA 405 increased basal GFR, assessed by inulin clearance, and attenuated the angiotensin II-induced decline in GFR. RTA 405 increased the filtration fraction, but did not affect arterial blood pressure or renal plasma flow. Glomeruli from RTA 405-treated rats were resistant to angiotensin II-induced volume reduction ex vivo. In cultured mesangial cells, angiotensin II-stimulated contraction was attenuated by RTA 405, in a dose- and time-dependent fashion. Further, Nrf2 targeted gene transcription (regulates antioxidant, anti-inflammatory, and cytoprotective responses) in mesangial cells was associated with decreased basal and reduced angiotensin II-stimulated hydrogen peroxide and calcium ion levels. These mechanisms contribute to the GFR increase that occurs following treatment with RTA 405 in rats and may underlie the effect of bardoxolone methyl on the estimated GFR in patients.

Targeting albuminuria in arterial hypertension and diabetes

Targeting albuminuria in arterial hypertension and diabetes

Protein Diet and Estimated Glomerular Filtration Rate

Chronic kidney disease (CKD) is a common health problem worldwide. CKD staging or classification, together with patients’ prognosis and treatment plan depend on the patients’ kidney function which is assessed by measurement of glomerular filtration rate (GFR). Estimated GFR can be obtained using serum or plasma creatinine as a main variable in equations or formulae such as Cockcroft-Gault equation, MDRD equation (Modification of Diet in Renal Disease), the Schwartz and Counahan-Barratt formulae. These equations, though widely accepted, still have to be adjusted or validated among different groups of patients according to the variation in some factors such as race, diet, and genetic heterogenicity. Diet, especially the high protein load, can affect GFR representing the renal functional reserve. A high protein diet can cause an increase in GFR that lasts for many hours. Long-term consumption of vegetarian diet which is low in protein and contains only protein from plant sources can cause a low baseline GFR while the renal functional reserve is still preserved. This paper aims to remind of the role of protein diet effect on GFR measurement especially when assessing the renal function in vegetarians or individuals on long-term low-protein intake.

Nle3,d-Phe6]-γ2-melanocyte-stimulating hormone possesses the renal excretory but not the cardiovascular actions of the native γ2-melanocyte-stimulating hormone in anaesthetized rats

The present study compared the cardiovascular and renal actions of γ(2) -melanocyte-stimulating hormone (γ(2) MSH) with those of the synthetic analogue [Nle(3) ,d-Phe(6) ]-γ(2) MSH (NDP-γ(2) MSH) and explored the effects of high dietary salt intake on the renal actions of NDP-γ(2) MSH. Both peptides were infused systemically (3-1000 nmol/kg) and intrarenally (500 fmol/min) into innervated and renally denervated rats fed either a normal (0.4% NaCl) or high-salt (4% NaCl; HS) diet. Mean arterial pressure (MAP), glomerular filtration rate (GFR), urinary sodium excretion (U(N) (a) V), urinary output (UV) and fractional sodium excretion were determined, as was expression of the melanocortin MC(3) receptor in inner medullary collecting duct (IMCD) epithelial cells. Both renal and systemic infusion of γ(2) MSH increased MAP by 23 ± 2% and 54 ± 4%, respectively, but equivalent doses of NDP-γ(2) MSH had no significant pressor effects. Both peptides had similar natriuretic and diuretic effects in rats fed a normal salt diet. However, NDP-γ(2) MSH increased U(N) (a) V and UV by two- to threefold in rats fed the normal salt diet and by six- to sevenfold in rats fed the HS diet. Furthermore, NDP-γ(2) MSH induced a 3.5-fold increase in GFR only in rats fed the HS diet. These renal effects of NDP-γ(2) MSH were not abolished by prior renal denervation. Rats fed the HS diet also exhibited a 4.5-fold increase in MC(3) receptor expression in IMCD epithelial cells. Intrarenal infusion of NDP-γ(2) MSH induced the natriuretic but not the cardiovascular effects exhibited by γ(2) MSH. The renal activities may be attributed to a direct binding of NDP-γ(2) MSH to MC(3) receptors expressed in IMCD cells, leading to a potent natriuretic effect that is independent of renal innervation.

ABCB1 C3435T Genetic Polymorphism on Population Pharmacokinetics of Methotrexate After Hematopoietic Stem Cell Transplantation in Korean Patients: A Prospective Analysis

BackgroundMethotrexate (MTX) is often used to prevent graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (HSCT). However, MTX has great pharmacokinetic variability and its use can result in fatal complications and/or infections after HSCT. ObjectivesThe purposes of this study were to build a population pharmacokinetic model of MTX treatment in Korean patients who have undergone HSCT and to identify covariates, including genetic polymorphisms, that affect the pharmacokinetic properties of MTX. MethodsClinical characteristics and MTX concentration data for 20 post-HSCT patients were collected. For each patient, ABCB1, ABCC2, ATIC, GGH, MTHFR, and TYMS genotyping was performed. Population pharmacokinetic analysis was performed using the NONMEM program. Analysis of MTX pharmacokinetic properties was accomplished using a 2-compartment pharmacokinetic model that incorporated first-order conditional estimation methods with interaction. The effects of a variety of demographic and genetic factors on MTX disposition were investigated. ResultsThe study population consisted of 12 men (60%) and 8 women (40%). Median age and body weight were 28 years (range, 18–49 years) and 55.6 kg (range, 44.8–80.8 kg), respectively. Within the study population, the estimated mean MTX clearance (CL) was 7.08 L/h, whereas the mean central compartment volume (V1) of MTX distribution was 19.4 L. MTX CL was significantly affected by glomerular filtration rate (GFR), penicillin use, and the ABCB1 3435 genotype. Interindividual variabilities for CL and V1 were 21.6% and 73.3%. A 10-mL/min GFR increase was associated with a 32% increase in mean MTX CL, whereas penicillin use was associated with a decrease in MTX CL of 61%. MTX CL was significantly greater (by ∼21%) in patients with the ABCB1 3435 CC and CT genotype than in those with the ABCB1 3435 TT genotype (P < 0.001). ConclusionsThere was great interindividual variation in MTX pharmacokinetic properties in patients who had undergone HSCT. GFR, concurrent penicillin use, and the presence of the ABCB1 3435 C<T genotypes significantly affected MTX CL. The MTX population pharmacokinetic model developed here may provide useful information for individualizing MTX therapy after HSCT.

Nle3, D‐Phe6]‐gamma melanocyte stimulating hormone (NDP γMSH), increases glomerular filtration rate (GFR) in high salt fed rats

This study examined the cardiovascular and renal actions of the natriuretic peptide γMSH with those of a synthetic analogue, NDP‐γMSH.Both γMSH and NDP‐γMSH were infused systemically (3–1000 nmol/kg) and intrarenally (500 fmol/min) into innervated and renally denervated normal and high salt fed rats. The effect of the infusion of these peptides on mean arterial pressure (MAP), urinary sodium excretion, urinary output, GFR and fractional sodium excretion was measured.Both renal and systemic infusion of γMSH increased MAP by 23±2% and 54±4% respectively but no pressor effects were observed upon renal or systemic infusion of NDP‐γMSH. The analogue increased urine flow and sodium excretion by 2–3 fold in fed a normal salt (0.4% Na+) diet and by 6–7 fold in rats fed a high salt (4% Na+) diet and induced a 3.5‐fold increase in GFR in high salt fed rats compared to normal salt fed controls. These renal effects of NDP‐γMSH were not abolished by prior renal denervation.NDP‐γMSH possessed the natriuretic but not the cardiovascular properties of γMSH. These natriuretic effects occur independently of renal innervation suggesting a direct effect of NDP‐γMSH on the kidney.

2194 RENAL PARENCHYMAL VOLUME INCREASES AFTER CONTRALATERAL NEPHRECTOMY: ASSESSMENT USING THREE-DIMENSIONAL ULTRASONOGRAPHY

You have accessJournal of UrologyImaging/Radiology: Uroradiology II1 Apr 20122194 RENAL PARENCHYMAL VOLUME INCREASES AFTER CONTRALATERAL NEPHRECTOMY: ASSESSMENT USING THREE-DIMENSIONAL ULTRASONOGRAPHY Majima Tsuyoshi, Hattori Ryohei, Funahashi Yasuhito, Yamamoto Tokunori, and Gotoh Momokazu Majima TsuyoshiMajima Tsuyoshi Nagoya, Japan More articles by this author , Hattori RyoheiHattori Ryohei Nagoya, Japan More articles by this author , Funahashi YasuhitoFunahashi Yasuhito Nagoya, Japan More articles by this author , Yamamoto TokunoriYamamoto Tokunori Nagoya, Japan More articles by this author , and Gotoh MomokazuGotoh Momokazu Nagoya, Japan More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2012.02.2368AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Removal of 1 kidney induces immediate hemodynamic changes in rats, which results in the increase of the contralateral kidney volume; however, this has not been confirmed in humans. The purpose of this study is to measure renal parenchymal volume (RPV) before and after unilateral nephrectomy and to clarify the relationship between changes of RPV and renal function. METHODS Forty-six consecutive patients undergoing unilateral nephrectomy were included. Three-dimensional ultrasonography (3D-US) was performed using LOGIQ7 ultrasound unit with a 2.0−5.0 MHz volume convex probe and RPV was calculated. We performed 3D-US before surgery (n = 46) and at 4.3 ± 1.9 hours (n = 46), 2 days (n = 39), and 7 days (n = 43) after surgery. For five patients who received open surgery in the supine position, we also performed 3D-US every 30 min, starting just before the renal artery transection. RESULTS The mean RPV of the remaining kidney was 104.7 ml before surgery, 116.1 ml (+13.2%) at 4.3 hours, 122.7 ml (+18.2%) at 2 days, and 117.6 ml (+13.3%) at 7 days after surgery. Sequential volume measurements during surgery (n = 5) revealed that transection of the renal artery was followed by an increase in RPV on the contralateral side at 60−90 min (Fig. 1). Multivariate regression analysis revealed that RPV was positively associated with single kidney glomerular filtration rate (GFR) and body surface area (BSA) both in the preoperative and postoperative states (Table 1). An increase in the single-kidney GFR was not seen at 2 years in patients with an RPV increase of <5% at 1 week (102.9 ± 8.4%, P = 0.322), but was still significant in the other patients (115.5 ± 21.0%, P < 0.001). Table 1. Statistical significance of preoperative factors related to RPV increase at 1 week Univariate analysis Multivariate analysis<> β p-value β p-value Gender -0.080 0.610 -0.058 0.700 Age 0.011 0.945 -0.074 0.654 BSA -0.062 0.694 0.347 0.027 RPV in the remaining kidney -0.527 <0.001 -0.804 <0.001 RPV in the resected kidney -0.194 0.223 -0.184 0.340 Single-kidney GFR in the remaining kidney -0.295 0.058 0.148 0.385 Single-kidney GFR in the resected kidney 0.114 0.471 0.349 0.013 Hypertension -0.104 0.506 -0.176 0.197 Diabetes mellitus 0.115 0.462 0.010 0.940 RPV; renal parenchymal volume, BSA; body surface area, GFR; glomerular filtration rate. CONCLUSIONS RPV began to increase at 60-90 min after nephrectomy and remained stable for at least 1 week. The change in RPV increased when the remaining kidney was small, the removed kidney had greater function, and BSA was large. The extent of the increase in RPV 1 week after nephrectomy may predict future deterioration in renal function. © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 187Issue 4SApril 2012Page: e884-e885 Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.MetricsAuthor Information Majima Tsuyoshi Nagoya, Japan More articles by this author Hattori Ryohei Nagoya, Japan More articles by this author Funahashi Yasuhito Nagoya, Japan More articles by this author Yamamoto Tokunori Nagoya, Japan More articles by this author Gotoh Momokazu Nagoya, Japan More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

759 Safety Evaluation of the HeartWare MVAD Pump in the Pericardial Position in an Ovine Model

Purpose: Clinical studies have shown that renal function is either maintained or significantly improved while supported with a continuous flow left ventricular assist device (CF-LVAD). Due to the lack of strict criteria and risk of acute renal injury after cardiac surgery some centers have been reluctant to offer this option to patients with advanced chronic kidney disease (CKD). We examined the clinical outcomes in patients with stage 3 or 4 CKD implanted with a CF-LVAD. Methods and Materials: All patients (n 138) who were supported 365 days with a CF-LVAD between March 2005 and November 2010 at our institution were retrospectively analyzed. Renal function was assessed using the Modification of Diet in Renal Disease (MDRD) derived glomerular filtration rate (GFR) ml/min/1.73 m. Patients with an average GFR 35 ml/mt on three consecutive days with the last GFR collected on the day of implant were included. Preoperative urinalysis and renal ultrasound were performed. Results: Patients (n 11) were 72% male, 55% white, average age 63 with an average baseline GFR 29.8 ml/mt ( 5.8 ml/mt) while on inotropes medically optimized in a critical care unit. All patients had a history of hypertension; seven (64%) patients were diabetic, 18% had documented protienuria of at least one plus on dipstick and one patient required renal replacement therapy within 6 months prior to LVAD placement for volume overload and metabolic derangements. There was a significant improvement (p .05) in renal function 30 days post-implant with an increase in average GFR (29.8 5.8 ml/mt to 41.3 11.7 ml/mt) and Cr (2.4 .53 to 1.8 .60) which was maintained out to one year. Survival at 365 days was 91% with no patients requiring dialysis. Conclusions: Patients with a GFR 35 supported with a LVAD had significant improvement in their renal function 30 days post implant which was sustained out to one year. In addition the one year survival rate for patients with advanced CKD is superior to recent multicenter results with the HeartMate II for destination therapy.