Can we slow the progression of chronic kidney disease?
ABSTRACT Childhood chronic kidney disease usually progresses towards end-stage renal failure once a critical impairment of renal function has occurred. This process is largely independent of the underlying renal disease. Recent clinical trials have provided evidence that the progressive course of chronic kidney disease can be slowed substantially by pharmacological intervention.
Hypertension and proteinuria are the most important independent risk factors for renal disease progression in both adult and pediatric nephropathies. Pharmacological blockade of the renin-angiotensin system provides efficient control of blood pressure and proteinuria, and superior long-term renoprotection compared with other antihypertensive agents. Recent pediatric evidence supports the renoprotective efficacy of tight blood pressure control aiming for the low-normal range. In addition, promising preliminary findings suggest an additional renoprotective potential by correction of metabolic acidosis and hyperuricemia and by administration of antiproliferative and antioxidative drugs.
Pharmacological renoprotection currently focuses on antihypertensive and antiproteinuric treatment by blockade of the renin-angiotensin system. Intensified blood pressure control can improve 5-year renal survival by 35% in children with chronic kidney disease. Additional complementary strategies under current clinical evaluation bear potential to improve renal survival even further.
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ABSTRACT: Chronic kidney disease in the pediatric population has been increasing. Early detection and treatment can slow down the progression of kidney disease and help prevent the development of end stage renal disease. In addition, as the kidney function declines, there are many pathophysiologic interactions with other organ systems that need to be monitored and treated. In particular, because of impaired vitamin D metabolism, calcium and phosphorus homeostasis is dysregulated and results in secondary bone disease. Anemia is common due to a number of factors including impaired erythropoietin production. Growth is often impacted by chronic kidney disease but can be improved by proper treatment. Complications of chronic kidney disease can be minimized by proper monitoring and treatment of these parameters. The general pediatrician plays a critical role in this process.International Journal of Pediatrics 01/2012; 2012:943904.
Article: Prevention of renal injury and endothelial dysfunction by chronic L-arginine and antioxidant treatment.[show abstract] [hide abstract]
ABSTRACT: We evaluated the effects of vitamins with antioxidant properties (a combination of vitamins C and E) and L-arginine treatment on renal failure in mice by measuring survival rate. The molecular changes were elucidated by determining endothelial tetrahydrobiopterin (BH4) levels and nitric oxide synthase (eNOS) mRNA expression in mice with renal ablation. Previous studies have shown that endothelial dysfunction in 5/6 nephrectomized mice is associated with decreased nitric oxide (NO) bioavailability and increased vascular superoxide production. WTC57 mice were divided into three groups: Group 1 was the sham-operated group (C); Group 2 was the 5/6 nephrectomized group (Nfx); and Group 3 was a group of 5/6 nephrectomized mice, treated with L-arginine and vitamins with antioxidant properties (NfxTx; 200 mg/kg L-arginine, 83 mg/kg vitamin C, and 46.6 mg/kg vitamin E). After 20 weeks of treatment, urinary protein excretion, blood pressure, BH4 and dihydrobiopterin (BH2) levels, eNOS mRNA, oxidative stress, and survival rate were determined. An increase in urinary protein excretion, blood pressure, and oxidative stress was prevented in the NfxTx group, but not in the Nfx group. BH4 and eNOS mRNA expression was increased by 32% and 78%, respectively, in the NfxTx group. Furthermore, the treatment increased the survival rate by 33%. Our results indicate that under normal conditions, NO appears to protect renal function. However, this NO-dependent protection is lost during kidney failure, probably due to increased reactive oxygen species synthesis. The treatment restores the viability of NO and prevents the BH4 oxidation. Therefore, this treatment may represent a therapeutic approach for the management of kidney disease.Renal Failure 01/2011; 33(1):47-53. · 0.82 Impact Factor