Association of obesity and muscle mass with risk of albuminuria in renal transplant recipients.

BACKGROUND: Increased albuminuria is a predictor of graft loss in kidney graft recipients. It is unknown whether obesity is an independent risk factor for the development of increased albuminuria in this population. The aim of this study was to elucidate the association between obesity and albuminuria in renal transplant recipients. METHODS: We enrolled 330 renal transplant recipients and prospectively collected demographic, anthropomorphic, clinical and laboratory variables susceptible to influence albumin excretion. The outcome was albuminuria, measured using accurately timed urine collections. Data from 201 patients were analyzed after exclusion of participants with missing data and patients enrolled less than 6 months since renal transplantation. Analysis was carried out for an early and a late period, defined according to the 2.4-year median follow-up time. RESULTS: Body mass index (BMI), waist circumference and urinary creatinine excretion rate were independent predictors of albuminuria in the late post-transplant period, indicating that the predictive value of body mass index for albuminuria is related to both increased abdominal fat mass and increased muscle mass. BMI was an independent predictor of microalbuminuria. Waist circumference and urinary creatinine were independent predictors of microalbuminuria for values above certain cutoffs: 110% of the accepted thresholds defining abdominal obesity and 1500 mg/day, respectively. CONCLUSIONS: These associations, which have not previously been reported, suggest, but do not prove, that an imbalance between metabolic demand and nephron mass may be responsible for increased albuminuria in the renal transplant population.

25-Hydroxyvitamin D Inhibits Hepatitis C Virus Production in Hepatocellular Carcinoma Cell Line by a Vitamin D Receptor-Independent Mechanism.

Previously, we have reported that the active vitamin D metabolite, calcitriol and vitamin D3 (cholecalciferol), both remarkably inhibit hepatitis C virus production. The mechanism by which vitamin D3 exerts its effect is puzzling due to the low levels of calcitriol produced in vitamin D3-treated Huh7.5 cells. In this study, we aimed to explore the mechanism of vitamin D3 anti-hepatitis C virus effect. We show that vitamin D3 activity is not mediated by its metabolic conversion to calcitriol, but may be due to its primary metabolic product 25(OH)D3. This is inferred from the findings that 25(OH)D3 could inhibit hepatitis C virus production in our system, and that adequate concentrations needed to exert this effect are produced in Huh7.5 cells treated with vitamin D3. Using the CRISPR-Cas9 editing technology to knockout the vitamin D receptor, we found that the antiviral activity of vitamin D3 and 25(OH)D3 was not impaired in the vitamin D receptor knockout cells. This result indicates that 25(OH)D3 anti-hepatitis C virus effect is exerted by a vitamin D receptor-independent mode of action. The possibility that vitamin D3 and 25(OH)D3, being 3ß-hydroxysteroids, affect hepatitis C virus production by direct inhibition of the Hedgehog pathway in a vitamin D receptor-independent manner was ruled out. Taken together, this study proposes a novel mode of action for the anti-hepatitis C virus activity of vitamin D3 that is mediated by 25(OH)D3 in a vitamin D receptor-independent mechanism.

A New Cutoff for Abnormal Proteinuria in Diabetes Mellitus Patients: Relationship to Albuminuria.

BACKGROUND: Proteinuria and albuminuria are markers of kidney injury and function, serving as a screening test as well as a means of assessing the degree of kidney injury and risk for cardiovascular disease and death in both the diabetic and the non-diabetic general population. OBJECTIVES: To evaluate the association between proteinuria below 300 mg/24 hours and albuminuria, as well as a possible association with kidney function in patients with diabetes mellitus (DM). METHODS: The medical files of patients with type 1 and type 2 DM with proteinuria below 300 mg/24 hours at three different visits to the Diabetic Nephropathy Clinic were screened. This involved 245 patient files and 723 visits. The data collected included demographics; protein, albumin and creatinine levels in urine collections; blood biochemistry; and clinical and treatment data. RESULTS: The association between proteinuria and albuminuria is non-linear. However, proteinuria in the range of 162-300 mg/24 hours was found to be linearly and significantly correlated to albuminuria (P < 0.001, r = 0.58). Proteinuria cutoff, based on albuminuria cutoff of 30 mg/24 hours, was found to be 160.5 mg/24 hr. Body mass index (BMI) was the sole independent predictor of proteinuria above 160.5 mg/24 hr. Changes in albuminuria, but not proteinuria, were associated with changes in creatinine clearance. CONCLUSIONS: A new cutoff value of 160.5 mg/hr was set empirically, for the first time, for abnormal proteinuria in diabetic patients. It appears that proteinuria below 300 mg/24 hr is not sufficient as a sole prognostic factor for kidney failure.

Effect of Acetazolamide on Obesity-Induced Glomerular Hyperfiltration: A Randomized Controlled Trial.

AIMS: Obesity is an important risk factor for the development of chronic kidney disease. One of the major factors involved in the pathogenesis of obesity-associated kidney disease is glomerular hyperfiltration. Increasing salt-delivery to the macula densa is expected to decrease glomerular filtration rate (GFR) by activating tubuloglomerular feedback. Acetazolamide, a carbonic anhydrase inhibitor which inhibits salt reabsorption in the proximal tubule, increases distal salt delivery. Its effects on obesity-related glomerular hyperfiltration have not previously been studied. The aim of this investigation was to evaluate whether administration of acetazolamide to obese non diabetic subjects reduces glomerular hyperfiltration. MATERIALS AND METHODS: The study was performed using a randomized double-blind crossover design. Obese non-diabetic men with glomerular hyperfiltration were randomized to receive intravenously either acetazolamide or furosemide at equipotent doses. Twelve subjects received the allocated medications. Two weeks later, the same subjects received the drug which they had not received during the first study. Inulin clearance, p-aminohippuric acid clearance and fractional lithium excretion were measured before and after medications administration. The primary end point was a decrease in GFR, measured as inulin clearance. RESULTS: GFR decreased by 21% following acetazolamide and did not decrease following furosemide. Renal vascular resistance increased by 12% following acetazolamide, while it remained unchanged following furosemide administration. Natriuresis increased similarly following acetazolamide and furosemide administration. Sodium balance was similar in both groups. CONCLUSIONS: Intravenous acetazolamide decreased GFR in obese non-diabetic men with glomerular hyperfiltration. Furosemide, administered at equipotent dose, did not affect GFR, suggesting that acetazolamide reduced glomerular hyperfiltration by activating tubuloglomerular feedback. TRIAL REGISTRATION: ClinicalTrials.gov NCT01146288.

An intradialytic increase in serum interleukin-6 levels is associated with an increased mortality in hemodialysis patients.

BACKGROUND: The inflammatory marker interleukin-6 (IL-6) increases early in the inflammatory cascade. The aim of this study was to evaluate whether an increase in serum IL-6 levels during a hemodialysis (HD) session is associated with mortality. METHODS: 57 adult patients treated with HD for more than 1 month were prospectively studied over a 3-year follow-up period. Demographic and clinical data were collected and blood samples were drawn before and after a midweek HD session. Events of death and censoring were recorded. RESULTS: During the 3-year follow-up, 50.8% of the patients died. In univariate Cox regression analysis, an increase in IL-6 levels during HD was associated with an increased mortality (HR 1.41 per pg/ml; 95% CI 1.06 to 1.88; P = .017). In multivariate Cox models, the only independent predictors of all-cause mortality were: an increase in IL-6 levels during dialysis (HR 1.46 per pg/ml; 95% CI 1.08 to 1.98; P = .014), higher baseline C-reactive protein (CRP) levels and older age. When predictors of an increase in serum IL-6 levels during HD were introduced into the model, mortality was still significantly associated with IL-6 elevation during dialysis (HR 1.47 per pg/ml, 95% CI 1.01 to 2.14; P = .045). CONCLUSIONS: A rise in serum IL-6 levels during a single HD session is associated with a higher mortality among HD patients, independent of predialysis CRP or IL-6 levels. The results may imply the presence of an intradialytic inflammatory response that affects survival in HD patients.

GFR in Patients with ß-Thalassemia Major.

BACKGROUND AND OBJECTIVES: Patients with ß-thalassemia major (TM) may have tubular dysfunction and glomerular dysfunction, primarily hyperfiltration, based on eGFR. Assessment of GFR based on serum creatinine concentration may overestimate GFR in these patients. This study sought to determine GFR by using inulin clearance and compare it with measured creatinine clearance (Ccr) and eGFR. DESIGN, SETTING, PARTICIPANTS & MEASUREMENTS: Patients followed up in an Israeli thalassemia clinic who had been regularly transfused for years and treated with deferasirox were included in the study. They were studied by inulin clearance, Ccr, the CKD Epidemiology Collaboration and the Modification of Diet in Renal Disease equations for eGFR, and the Cockcroft-Gault estimation for Ccr. Expected creatinine excretion rate and tubular creatinine secretion rate were calculated. RESULTS: Nine white patients were studied. Results, given as medians, were as follows: serum creatinine was 0.59 mg/dl (below normal limits); GFR was low (76.6 ml/min per 1.73 m(2)) and reached the level of CKD; Ccr was 134.9 ml/min per 1.73 m(2), higher than the GFR because of a tubular creatinine secretion rate of 30.3 ml/min per 1.73 m(2) (this accounted for 40% of the Ccr); and eGFR calculated by the CKD Epidemiology Collaboration and Modification of Diet in Renal Disease equations and Cockcroft-Gault-estimated Ccr were 133, 141, and 168 ml/min per 1.73 m(2), respectively. These latter values were significantly higher than the GFR, reaching the hyperfiltration range, and indicated that the estimation techniques were clinically unacceptable as a method for measuring kidney function compared with the GFR according to Bland and Altman analyses. CONCLUSIONS: Contrary to previous reports, patients in this study with TM had normal or reduced GFR. The estimating methods showed erroneous overestimation of GFR and were clinically unacceptable for GFR measurements in patients with TM by Bland and Altman analysis. Therefore, more accurate methods should be used for early detection of reduced GFR and prevention of its further decline toward CKD in these patients.

Changes in inflammatory markers during a hemodialysis session and their relation to vascular access type.

PURPOSE: In an attempt to better understand the relationship between vascular access and inflammation we assessed the effect of vascular access on inflammatory markers changes during hemodialysis (HD) session. METHODS: Fifty HD patients were included: 23 patients with central venous catheters (CVC) and 27 patients with arteriovenous fistulas (AVF). Blood samples for high sensitivity C-reactive protein (hsCRP), Interleukin 6 (IL-6), and Tumor Necrosis Factor α (TNF α) were collected before and after HD session. The outcome was the change in the inflammatory markers during the dialysis. RESULTS: Predialysis hsCRP levels were high in 70% of patients, without differences between the groups. Predialysis values were also similar in the two groups for IL-6 and TNF α. There was no increase in hsCRP values following HD and no difference between the change from baseline values in the CVC and AVF groups (-0.01±0.09 mg/dL and -0.01±0.13 mg/dL, respectively [P=.95]). IL-6 values increased during the HD session in the AVF group and non-significantly decreased in the CVC group. The change from baseline values was statistically significantly greater in the AVF group compared to the CVC group (0.76±1.44 ng/mL and -0.52±1.66 ng/mL, respectively, P=.006). TNF α values were significantly decreased in the CVC group and were not changed in the AVF group. The decrease from baseline values was not different between the groups. CONCLUSIONS: Chronic inflammation is present in most HD patients. No increase in pro-inflammatory parameters was seen after a HD session in patients treated via CVC or AVF.

Vitamin D: an innate antiviral agent suppressing hepatitis C virus in human hepatocytes.

UNLABELLED: Vitamin D supplementation was reported to improve the probability of achieving a sustained virological response when combined with antiviral treatment against hepatitis C virus (HCV). Our aim was to determine the in vitro potential of vitamin D to inhibit HCV infectious virus production and explore the mechanism(s) of inhibition. Here we show that vitamin D(3) remarkably inhibits HCV production in Huh7.5 hepatoma cells. These cells express CYP27B1, the gene encoding for the enzyme responsible for the synthesis of the vitamin D hormonally active metabolite, calcitriol. Treatment with vitamin D(3) resulted in calcitriol production and induction of calcitriol target gene CYP24A1, indicating that these cells contain the full machinery for vitamin D metabolism and activity. Notably, treatment with calcitriol resulted in HCV inhibition. Collectively, these findings suggest that vitamin D(3) has an antiviral activity which is mediated by its active metabolite. This antiviral activity involves the induction of the interferon signaling pathway, resulting in expression of interferon-ß and the interferon-stimulated gene, MxA. Intriguingly, HCV infection increased calcitriol production by inhibiting CYP24A1 induction, the enzyme responsible for the first step in calcitriol catabolism. Importantly, the combination of vitamin D(3) or calcitriol and interferon-α synergistically inhibited viral production. CONCLUSION: This study demonstrates for the first time a direct antiviral effect of vitamin D in an in vitro infectious virus production system. It proposes an interplay between the hepatic vitamin D endocrine system and HCV, suggesting that vitamin D has a role as a natural antiviral mediator. Importantly, our study implies that vitamin D might have an interferon-sparing effect, thus improving antiviral treatment of HCV-infected patients.

The urine albumin-to-creatinine ratio: assessment of its performance in the renal transplant recipient population.

BACKGROUND AND OBJECTIVES: Microalbuminuria predicts graft loss and death in the renal transplant population. Measurement of the urinary albumin-to-creatinine ratio (UACR) is recommended for its detection. There is uncertainty regarding the optimal UACR cutoff values. Few studies have examined the accuracy of UACR in the general population and none have been conducted in renal transplant recipients. The aim of this study is to determine the performance of UACR in the renal transplant population. DESIGN, SETTING, PARTICIPANTS & MEASUREMENTS: Renal transplant recipients with a daily urinary albumin excretion rate of up to 300 mg accurately carried out a 24-hour urine collection and provided a morning urine sample for the measurement of albuminuria and UACR. The performance measures of UACR for the detection of microalbuminuria (30 to 300 mg/d) were calculated using different cutoffs. RESULTS: Median albuminuria was 23 mg/d, and median UACR was 17 mg/g. The area under the receiver-operating characteristic curve was 0.94 in men and 0.98 in women. The optimal cutoff was 21 mg/g in men and 24 mg/g in women. In men, the 30-, 17-, and 21-mg/g cutoffs provided a sensitivity of 0.79, 0.89, and 0.87. In women, the 30-, 25-, and 24-mg/g cutoffs provided a sensitivity of 0.90, 0.97, and 1.0. CONCLUSIONS: These data show that in the renal transplant population, lower gender-specific cutoffs should be used for the detection of microalbuminuria than the recommended 30-mg/g cutoff. These data support the need for a reappraisal of the 30-mg/g cutoff for the detection of microalbuminuria.

Obesity-induced glomerular hyperfiltration: its involvement in the pathogenesis of tubular sodium reabsorption.

BACKGROUND: Obesity is associated with hypertension and glomerular hyperfiltration. A major mechanism responsible for the obesity-associated hypertension is renal salt retention. An increased glomerular filtration fraction (FF) is expected to raise postglomerular oncotic pressure and to increase proximal tubular sodium reabsorption. The aim of the present study was to verify whether obesity-associated hyperfiltration leads to increased postglomerular oncotic pressure and increased proximal sodium reabsorption. METHODS: Twelve obese subjects (BMI >36) and 19 lean subjects participated in the study. They underwent measurement of glomerular filtration rate (GFR), renal plasma flow (RPF) and fractional excretion of lithium (FE Li). RESULTS: GFR, RPF and FF were 61%, 28% and 29% higher, respectively, in the obese than in the control group (P < 0.00001 for GFR, P < 0.005 for RPF and P < 0.00005 for FF). Half of the obese group had increased FF with increased GFR, while the other half had normal FF with high-normal or increased GFR. Postglomerular oncotic pressure was 13% higher (P < 0.03) and FE Li was 33% lower (P < 0.005) in the obese group with high FF than in the lean group. Postglomerular oncotic pressure and FE Li were normal in the obese group with normal FF. CONCLUSIONS: These results suggest that glomerular hyperfiltration may lead to increased proximal tubular sodium reabsorption in the obese.

Renin-angiotensin system blockade prevents the increase in plasma transforming growth factor beta 1, and reduces proteinuria and kidney hypertrophy in the streptozotocin-diabetic rat.

INTRODUCTION: Combination therapy with angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) is used to improve renal outcome achieved by monotherapy in diabetic patients. In addition, interference with the renin-angiotensin system (RAS) reduced expression and excretion of transforming growth factor beta 1 (TGF-beta 1) in diabetic nephropathy. The aim of this study was to investigate the effects of interrupting the RAS by ACE inhibitor (ACE-I) or ARB monotherapy or by combination therapy on proteinuria, kidney hypertrophy and plasma TGF-beta 1 in diabetic rats. MATERIALS AND METHODS: Forty-one male Wistar rats were allocated to five groups: 1 = control rats, 2 = diabetic rats (streptozotocin [STZ] 55 mg/kg), 3 = diabetic rats as above receiving enalapril (20 mg/kg/day), 4 = diabetic rats receiving losartan (80 mg/kg/day), 5 = diabetic rats receiving both losartan and enalapril. The study lasted 60 days. RESULTS: Urinary protein excretion, kidney weight, serum ACE activity and plasma TGF-beta1 increased significantly in untreated diabetic rats compared with controls. Administration of losartan, enalapril, or both for 60 days prevented these changes. Furthermore, combined therapy for 30 days normalised urinary protein excretion, while monotherapy did not. Losartan inhibited serum ACE activity both in vivo and in vitro. Plasma TGF-beta 1 levels were positively correlated with blood glucose levels (r=0.4059) and with urinary protein excretion (r=0.3558). CONCLUSIONS: Combination therapy with losartan and enalapril was more effective than monotherapy with either drug in achieving an early antiproteinuric response. Long-term treatment with losartan was as effective as the combined treatment, possibly due to a dual inhibitory effect on the RAS. The antiproteinuric effect may be related, in part, to reduced TGF-beta 1.

Coenzyme Q10 in patients with end-stage heart failure awaiting cardiac transplantation: a randomized, placebo-controlled study.

BACKGROUND: The number of patients awaiting heart transplantation is increasing in proportion to the waiting period for a donor. Studies have shown that coenzyme Q10 (CoQ10) has a beneficial effect on patients with heart failure. HYPOTHESIS: The purpose of the present double-blind, placebo-controlled, randomized study was to assess the effect of CoQ10 on patients with end-stage heart failure and to determine if CoQ10 can improve the pharmacological bridge to heart transplantation. METHODS: A prospective double-blind design was used. Thirty-two patients with end-stage heart failure awaiting heart transplantation were randomly allocated to receive either 60 mg U/day of Ultrasome--CoQ10 (special preparation to increase intestinal absorption) or placebo for 3 months. All patients continued their regular medication regimen. Assessments included anamnesis with an extended questionnaire based partially on the Minnesota Living with Heart Failure Questionnaire, 6-min walk test, blood tests for atrial natriuretic factor (ANF) and tumor necrosis factor (TNF), and echocardiography. RESULTS: Twenty-seven patients completed the study. The study group showed significant improvement in the 6-min walk test and a decrease in dyspnea, New York Heart Association (NYHA) classification, nocturia, and fatigue. No significant changes were noted after 3 months of treatment in echocardiography parameters (dimensions and contractility of cardiac chambers) or ANF and TNF blood levels. CONCLUSIONS: The administration of CoQ10 to heart transplant candidates led to a significant improvement in functional status, clinical symptoms, and quality of life. However, there were no objective changes in echo measurements or ANF and TNF blood levels. Coenzyme Q10 may serve as an optional addition to the pharmacologic armamentarium of patients with end-stage heart failure. The apparent discrepancy between significant clinical improvement and unchanged cardiac status requires further investigation.

Insulin and losartan reduce proteinuria and renal hypertrophy in the pregnant diabetic rat.

This study was designed to investigate the effect of hyperglycemia and angiotensin II (AngII) on renal hypertrophy and proteinuria in the pregnant diabetic rat. Secondary objectives were to evaluate changes in components of the renin-angiotensin axis and the effects of administration of losartan on pregnancy outcome. Fifty-three pregnant rats were allocated to 6 groups (1) nondiabetic controls (n = 12), (2) nondiabetic controls administered losartan (70-80 mg/kg/day; n = 10), (3) rats in which intravenous streptozotocin (STZ) was used to induce diabetes (55 mg/kg on day 10 of pregnancy; n = 10), (4) diabetic rats treated with losartan (n = 7), (5) diabetic rats treated with insulin (4 U/day; n = 7), and (6) diabetic rats treated with insulin and losartan (n = 7). Urinary protein excretion measured 4 days after STZ was 4 times greater in the rats with STZ-induced diabetes and significantly less in diabetic rats given losartan, insulin, or both. Postpartum kidney weight was greater in the rats with STZ-induced diabetes (2.04 +/- 0.21 g) than in the controls (1.37 +/- 0.14 g; P <.05) and reduced in the diabetic rats given losartan, insulin, or both (1.57 +/- 0.22, 1.73 +/- 0.13, and 1.51 +/- 0.14 g, respectively; P <.05). Plasma levels of angiotensin II in rats given losartan were more than 3.5 times greater than those in controls (749 +/- 436, 596 +/- 323, 567 +/- 349, and 159 +/- 28 pg/mL; P <.001). Postpartum activity of angiotensin-converting enzyme was increased in the untreated diabetic rats compared with that in control rats (162 +/- 12 vs 117 +/- 16 nmol/mL/min; P <.05). This increase was abolished by treatment with losartan or insulin. The number of newborns and mean weight of each newborn was similar in all groups. In summary, administration of losartan or insulin prevented, in part, kidney hypertrophy and protein excretion in the diabetic pregnant rat. Losartan did not affect the number or weight of newborns. Because angiotensin II receptor-blockers are contraindicated in pregnancy, good control of diabetes through the use of insulin should be advantageous.

Involvement of human heparanase in the pathogenesis of diabetic nephropathy.

BACKGROUND: Decreased heparan sulfate proteoglycan content of the glomerular basement membrane has been described in proteinuric patients with diabetic nephropathy. Heparanase is an endo-beta-D-glucuronidase that cleaves negatively charged heparan sulfate side chains in the basement membrane and extracellular matrix. OBJECTIVES: To investigate whether urine from type I diabetic patients differs in heparanase activity from control subjects and whether resident glomerular cells could be the source of urinary heparanase. METHODS: Using soluble 35S-HSPG and sulfate-labeled extracellular matrix we assessed heparanase activity in human glomerular epithelial cells, rat mesangial cells, and urine from 73 type I diabetic patients. Heparanase activity resulted in the conversion of a high molecular weight sulfate-labeled HSPG into heparan sulfate degradation fragments as determined by gel filtration analysis. RESULTS: High heparanase activity was found in lysates of both epithelial and mesangial cells. Immunohistochemical staining localized the heparanase protein to both glomeruli capillaries and tubular epithelium. Heparanase activity was detected in the urine of 16% and 25% of the normoalbuminuric and microalbuminuric diabetic patients, respectively. Urine from 40 healthy individuals did not possess detectable heparanase. Urinary heparanase activity was associated with worse glycemic control. CONCLUSION: We suggest that heparanase enzyme participates in the tunover of glomerular HSPG. Hyperglycemia enhances heparanase activity and/or secretion in some diabetic patients, resulting in the loss of albumin permselective properties of the GBM.

The contribution of an arteriovenous access for hemodialysis to left ventricular hypertrophy.

BACKGROUND: The long-term isolated contribution of hemodialysis arteriovenous access (AVA) to cardiac hemodynamics has not been previously investigated in a prospective manner. METHODS: Twelve predialysis patients were studied before and 1 and 3 months after creation of a primary AVA. Evaluation included relevant clinical parameters, echocardiographic studies, and hemodynamic hormones. RESULTS: After creation of an AVA, there was no change in patient weight, blood pressure or hemoglobin level. Cardiac index increased and systemic vascular resistance decreased. Left ventricular mass (LVM) corrected to height increased from 63.8 +/- 5.5 to 68.9 +/- 4.9 g/m(2.7) at 1 month (P = 0.05) and 72.5 +/- 8.9 g/m(2.7) at 3 months (P < 0.05). This increase in LVM was accounted for mostly by an increase in interventricular septal thickness, whereas left ventricular end-diastolic diameter and posterior wall thickness did not change. The incidence of left ventricular hypertrophy (LVH) increased from 67% at baseline to 83% and 90% at 1 and 3 months, respectively. Left atrial area increased from 17.6 +/- 1.0 cm(2) at baseline to 19.7 +/- 1.3 cm(2) at 1 month (P < 0.01) and 20.2 +/- 1.2 cm(2) at 3 months (P < 0.05). Early diastolic transmitral flow increased from 68.0 +/- 4.2 cm/s at baseline to 85.6 +/- 7.3 and 89.2 +/- 6.5 cm/s at 1 and 3 months, respectively (P < 0.01). Inferior vena cava diameter increased at 1 month and did not change at 3 months. Plasma atrial natriuretic polypeptide levels increased from 268 +/- 35 pg/mL (87 +/- 11 pmol/L) at baseline to 461 +/- 63 pg/mL (150 +/- 20 pmol/L) at 1 month (P < 0.01) and 610 +/- 96 pg/mL (198 +/- 31 pmol/L) at 3 months (P < 0.01). Plasma renin activity and serum aldosterone levels decreased. Plasma angiotensin II, angiotensin-converting enzyme, and endothelin levels did not change. CONCLUSION: Creation of a hemodialysis AVA is independently associated with further progression of already existing LVH.