Search

AbstractBackground/Aims:The high morbidity and mortality rates in hemodialysis (HD) patients are due, at least in part, to their increased risk for cardiovascular diseases (CVD). This prospective study evaluated the effect of growth hormone (GH) on a number of CVD risk markers in adult patients on HD. Methods:139 HD patients were randomized to one of three GH doses or to placebo. Change from baseline in lean body mass (LBM), CVD risk markers (e.g. lipid profile, plasma homocysteine, inflammatory markers, blood pressure, IGF-I, IGFBP-3 and echocardiography) and correlations with serum IGF-I levels and body mass index were evaluated. Results:LBM increased in GH-treated groups compared with placebo (p < 0.001 pooled GH groups vs. placebo). IGF-I (p = 0.0027) and serum high-density-lipoprotein cholesterol levels (p = 0.038) increased with GH treatment. Serum low-density-lipoprotein cholesterol showed a trend to reduction. IGF-I was negatively correlated with plasma homocysteine levels (p = 0.01) and systolic blood pressure (p < 0.0001). Logistic regression analysis showed that interleukin-6, ghrelin and hematocrit values were significant determinants of all-cause mortality. Left ventricular mass was unchanged from baseline in GH-treated groups. Conclusion:In adult HD patients, GH treatment had a predominantly beneficial effect on CVD risk markers.Copyright © 2010 S. Karger AG, Basel

Angiotensin-converting enzyme inhibitors in native nephropathies reduce proteinuria and delay progression to renal failure. Data in renal transplantation remain limited. A negative effect on glomerular filtration rate was concluded in a recent systematic review.

Background A female with autosomal dominant polycystic kidney disease was followed up over the course of four pregnancies. Her first three pregnancies were unsuccessful. Her fourth pregnancy resulted in a live birth, but at what expense?Investigations The diagnosis of autosomal dominant polycystic kidney disease was confirmed by ultrasound imaging. Physical examination, blood pressure measurement, and urine and blood analyses were performed at each follow-up visit.Diagnosis Deterioration of renal function following multiple complicated pregnancies.Management Attention to blood pressure and proteinuria delayed initiation of dialysis, but effects of the number of pregnancies took their toll. The patient was started on hemodialysis and underwent renal transplantation.

Proteinuria is pathogenic to proximal tubular cells (PTC) and linked with progression to renal failure. The aim of this study was to determine the effects of human serum albumin (HSA) overload on the changes in gene and protein expression stimulated by oxidative stress in PTC and any interaction with ANG II that is pivotal in disease pathogenesis. Markers of oxidative stress, antioxidant defences, transcription factor activation, and the expression of stress-related genes were measured in human PTC (HK-2 cells) overloaded with either globulin-free fatty acid free (GF/FAF) HSA or globulin-free (GF) HSA. The effects of ANG II were also determined. HSA overload in HK-2 cells caused PTC hyperfunction, increased oxidative stress, and an upregulation of adaptive responses and stress-related genes. Some responses were common to both HSAs but others were unique to either HSA and unaffected by addition of ANG II or candesartan (a specific ANG II type 1 receptor blocker). ANG II also independently induced oxidative stress and upregulated other stress-related genes. HSA overload in HK-2 cells stimulated increased oxidative stress and upregulated changes in stress-related gene expression indicating new pathways of PTC injury that are not mediated via ANG II type 1 receptors.

Chronic allograft nephropathy (CAN) is commonly associated with proteinuria. In native nephropathies, proteinuria is linked with proximal renal tubular damage. This study uses regression analysis to link proteinuria with urinary N-acetyl-β-d-glucosaminidase (NAG) as a marker of tubular injury or hyperfunction in renal transplant patients.

Cyclosporine (CsA) is a substrate for the MDR-1gene product P-glycoprotein (P-gp). CsA efficacy may be modulated by lymphocyte P-gp expression levels. In this study, CsA inhibition of lymphocyte proliferation in whole-blood cultures ex vivo has been related to (1) lymphocyte P-gp expression and (2) the C3435T polymorphism in the MDR-1gene, which has been reported to alter P-gp function.

1. Progression to renal failure may be linked to the degree of proteinuria through tubulo-interstitial mechanisms. However, there are no data in man on the kinetics of proximal renal tubular protein catabolism or markers of tubular injury before and after lisinopril. We developed a method to allow such studies, and found increased tubular catabolism of 99mTc-labelled aprotinin (Trasylol) in patients with nephrotic range proteinuria which was associated with increased ammonia excretion. 2. In this study, 10 patients with mild renal impairment (51Cr-EDTA clearance 63.7 ± 8.3 ml · min−1 · 1.73 m−2) and heavy proteinuria (8.2 ± 2.3 g/24 h) were given lisinopril (10–20 mg) for 6 weeks. Renal tubular catabolism of intravenous aprotinin was measured before and after lisinopril by renal imaging and urinary excretion of the free radiolabel over 26 h. Fractional degradation was calculated from these data. Fresh timed urine collections were also analysed for ammonia excretion every fortnight from 6 weeks before treatment. Total urinary N-acetyl-β-d-glucosaminidase and the more tubulo-specific N-acetyl-β-d-glucosaminidase ‘A2’ isoenzyme were also measured. 3. After lisinopril proteinuria fell significantly as expected (from 9.5 ± 1.6 to 4.5 ± 1.0 g/24 h, P < 0.01). This was associated with a reduction in metabolism over 26 h (from 1.7 ± 0.1 to 1.2 ± 0.1% dose/h, P < 0.01) and in fractional degradation of aprotinin (from 0.08 ± 0.02 to 0.04 ± 0.007/h, P < 0.04). Ammonia excretion also fell significantly (from 1.2 ± 0.1 to 0.6 ± 0.1 mmol/h, P < 0.0001), as did both total urinary N-acetyl-β-d-glucosaminidase (P < 0.0001) and the N-acetyl-β-d-glucosaminidase ‘A2’ isoenzyme (P < 0.015). These observations after lisinopril treatment have not been described previously. There was no significant change in blood pressure nor in glomerular haemodynamics.

Markers of renal tubular injury are difficult to interpret in patients with proteinura. The 24-hour urinary N-acetyl-β-D-glucosaminidase (NAG) concentration was measured in 167 patients with dissimilar renal disease, function, and proteinuria. NAG isoenzymes were also separated in 69 patients, using a modified fast protein liquid chromatography technique. The ‘A2’ isoenzyme predominated at all levels of renal function and in all diagnostic groups. Urinary NAG and proteinuria were well correlated at all levels of renal function, as was NAG ‘A2’ isoenzyme. Proteinuria and urinary NAG were similarly correlated in patients with different glomerulonephritides, hypertensive nephrosclerosis, and chronic pyelonephritis, but not in those with diabetic nephropathy.

Oral sodium bicarbonate (NaHCO3) is widely used to treat acidosis in patients with renal failure. However, no data are available in man on the effects on proximal renal tubular protein catabolism or markers of tubular injury. We have developed methods to allow such studies, and both increased tubular catabolism of 99mTc-labelled aprotinin (Apr*), as well as tubular damage were found in association with increased ammonia (NH3) excretion in patients with nephrotic range proteinuria.We now examine the effects of reducing renal ammoniogenesis, without altering proteinuria, using oral NaHCO3 in 11 patients with mild/moderate renal impairment and proteinuria. Renal tubular catabolism of Apr* was measured before and after NaHCO3 by renal imaging (Kidney uptake, K % of dose) and urinary excretion of free 99mTcO4 (metabolism, Met % of dose/h) over 26 h. Fractional degradation (Frac) was calculated from Met/K (/h). Fresh urine was also analyzed for NH3 excretion every fortnight from 6/52 before treatment. Total urinary N-acetyl-β-D-glucoseaminidase (NAG) and the more tubulo-specific NAG “A2” were measured. 51CrEDTA clearance and 99mTc- MAG 3 TER were also assessed.After NaHCO3 Met over 26 h was significantly reduced (from 1.3 ± 0.2 % of dose/h to 0.9 ± 0.1 % dose/hrp <0.005), as was Frac of Apr* (from 0.06 ± .006/h to 0.04 ± 0.005/hrp <0.003). NH3 excretion also fell significantly (from 0.9 ± 0.2 mmol/h to 0.2 ± 0.05 mmol/hp <0.007), as did both total urinary NAG (from 169 μmol/24 h, 74-642 μmol/24 h to 79 μmol/ 24 h, 37-393 μmol/24 hp <0.01), and the NAG 'A2' isoenzyme (from 81.5 μmol/24 h, 20-472 μmol/24 h to 35.0 μmol/24 h, 6-388 μmol/24 hp <0.001). Proteinuria remained unaltered, and there was no change in blood pressure nor in glomerular haemodynamics. Oral NaHCO3 may thus pro-tect the proximal renal tubule and help delay renal disease progression.