Background/Aim: It is unknown to what extent uric acid (UA) may affect vessel function and participate in tubulointerstitial damage. We examined the relationship between intrarenal vessel function and serum UA and its excretion in association with urinary N-acetyl-β-D-glucosaminidase (NAG). Methods: In 50 IgA patients (mean age 34.7 ± 9.3 years) and 15 controls (mean age 33.5 ± 6.9 years) with a creatinine clearance of 99.4 ± 21.6 and 118.1 ± 17.2 ml/min, respectively, the renal vascular function was estimated based on the dopamine-induced glomerular filtration response (DIR; see text). The DIR was measured using two 120-min creatinine clearance values (before and after intravenous administration of 2 g/kg/min dopamine). Serum UA, triglycerides and cholesterol and urinary NAG (24 h) and protein and UA excretion were measured. Results: Patients with IgA nephropathy versus controls: DIR 8.80 ± 6.6 vs. 12.83% (p < 0.01), NAG 7.25 ± 3.30 vs. 4.69 ± 1.12 U/g creatinine (p < 0.01), and fractional UA excretion 7.80 ± 2.20 versus 6.29 ± 1.80% (p < 0.01). A negative correlation between DIR and NAG was found; regression analysis showed a more prominent relationship in the patients (NAG = 9.99 – 0.29x DIR) than in the controls (NAG = 5.50 – 0.06x DIR). UA and urate excretion and NAG in the patients correlated with DIR (r = –0.39, p < 0.02; r = –0.29, p < 0.04, and r = 0.59, p < 0.001, respectively). Multivariate analysis showed an association of DIR (R2 = 0.39) with NAG but not with proteinuria and UA and UA excretion; the NAG excretion (R2 = 0.56) correlated significantly with UA and DIR. Conclusion: It is suggested that UA plays a role, associated with tubular dysfunction, in the regulation of intrarenal vessel function.
Background: ω–3 polyunsaturated acids therapy is efficient in primary IgA nephropathy. It is unknown whether doses of ω–3 smaller than those given previously are still effective. The aim of the study was to examine the effect of ω–3 therapy on renal vascular function in relation to proteinuria and urinary excretion of N-acetyl-β-D-glucosaminidase (NAG). Methods: 20 IgA patients aged 36.5 ± 10.77 with creatinine clearance (Crcl) 105.71 ± 27.3 ml/min and proteinuria 3.31 ± 2.01 g/24 h were given orally 810 mg EPA and 540 mg DHA daily for 12 months. Before and at the end of the study, 24-hour proteinuria, serum homocysteine, and Crcl were measured. At the same time, renal vascular function was estimated as dopamine-induced glomerular filtration response (DIR). DIR was measured as: two 120-min lasting Crcl (before and during 2 µg/kg b.w./min i.v. dopamine). Results: The results obtained during follow-up were as follows (baseline vs. after therapy): DIR 14.9 ± 16.4 vs. 30.3 ± 14.3% (p < 0.01); urine protein 2.31 ± 2.01 vs. 1.31 ± 1.37 g/24 h (p < 0.01); (Crcl) 105.71 ± 27.3 vs. 103.9 ± 20.9 ml/min (n.s.); NAG 8.3 ± 1.8 vs. 6.0 ± 1.2 U/gcreat (p < 0.01), and homocysteine 16.2 ± 3.15 vs. 13.8 ± 2.6 µmol/l (p < 0.05). The only correlation found was linear correlation between basal DIR and DIR change (r = –0.570; p < 0.010) and basal NAG (r = –0.460; p < 0.50). Conclusions: ω–3 supplementation is associated with the improvement of both renal vascular function and tubule function.
Background: Albuminuria is the best and most readily available marker for glomerular damage and progressive renal function loss in patients with diabetic nephropathy. Recently, administration of the oral glycosaminoglycan sulodexide (a mixture of 80% fast-moving heparin and 20% dermatan sulphate) was shown to effectively decrease albumin excretion rate in diabetics with nephropathy. Aims: To evaluate whether the hypoalbuminuric effect of sulodexide is associated with improvement of the renal vascular or tubule function. Methods: Forty-five type 1 diabetic patients, affected by diabetic nephropathy with albuminuria for at least 5 years, were randomly allocated to sulodexide or untreated. Those allocated to sulodexide were given 100 mg of sulodexide daily for 120 days. Renal vascular function (DIR) and N-acetyl-β-D-glucosaminidase (NAG) excretion were estimated before and at the end of the study, the former in thesulodexide group only. DIR was measured as two Crcl lasting 120 min (before and during 2 µg/kg b.w. i.v. dopamine). Results: The analysis of trends during the study demonstrated a marked reduction of albuminuria in the sulodexide group (from 126.1 ± 15.41 to 93.6 ± 13.7 mg/day). DIR rose from 13.2 ± 2.1% to 15.44 ± 1.9% (relative increase: +16.9%), and NAG excretion showed a decreasing trend decreased in the sulodexide group only (from 5.1 ± 0.62 to 4.7 ± 0.40 U/gcreat). Conclusion: The findings presented in this study indicate for the first time that orally available sulodexide may favorably affect the renal vascular function in type 1 diabetic patients with nephropathy and microalbuminuria. The effect of sulodexide on NAG is strongly influenced by the baseline NAG values, with a significant NAG reduction in the patients with the highest baseline NAG values.
Background/Aims: Pharmacological inhibition of renin-angiotensin-aldosteron system (RAAS) may reduce proteinuria and the rate of chronic kidney disease progression. The aim was to compare the effects on albuminuria of the therapy with either: i) telmisartan 80 mg and aliskiren 300 mg, ii) telmisartan 80 mg and eplerenone 50 mg, iii) telmisartan 160 mg as monotherapy. Design and patients: Randomized, double-center, double-blind, cross-over, three treatments-three periods of 8 weeks each study. 18 patients with non-diabetic proteinuric CKD stage 1-3 completed the protocol. Results: There was significant difference in albuminuria between studied therapies (ANOVA; p<0.01). The combination therapy with telmisartan plus aliskiren decreased albuminuria more effectively than the treatment with telmisartan plus eplerenone and monotherapy with telmisartan 160 mg OD [376 mg/g creatinine (286-686) vs. 707 (502-1204) vs. 525 (318-763); post-hoc p<0.01 and p<0.05, respectively]. Conclusions: The study demonstrated that the combination therapy with angiotensin receptor blocker (ARB) and renin inhibitor was more effective in albuminuria lowering than the concomitant usage of ARB and mineralocorticoid receptor antagonist as well as than ARB in doses two-fold higher than usually used in treatment of hypertension in patients with non-diabetic CKD and that this higher antiproteinuric efficacy was independent on changes in blood pressure.
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