Chronic kidney disease (CKD) is defined as the presence of kidney damage or a glomerular filtration rate (GFR) <60 mL/min/1.73 m(2) for three or more months. Measurement of serum creatinine is the most commonly used method to evaluated kidney function, but it must be included in formulas to estimate GFR, adjusting for age, gender and ethnicity, such as the Modification of Diet in Renal Disease (MDRD) study equation. The performance of this equation is acceptable for patients with CKD but appears to under-estimate GFR in populations with unknown kidney status. A new formula has been developed recently. The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation appears to perform better than the MDRD equation. Cystatin C has been widely evaluated as a marker for GFR and seems to be more sensitive than creatinine. The aim of this review is to discuss the recommendations for detecting CKD, emphasizing the characteristics and limitations of GFR estimating equations and pitfalls in the evaluation of urinary albumin excretion.

In vitro prostaglandin (PG) and thromboxane B2 (TXB2) formation by isolated glomeruli from normotensive (N) and two-kidney, one-clip hypertensive (2K,1C) rats was determined. When calculated on the basis of glomerular protein content, PGE2, 6-keto-PGF1 alpha and TXB2 production of glomeruli from clipped kidneys was significantly greater than PG and TXB2 formation of glomeruli from the untouched kidneys. When PG and TXB2 formation was calculated per amount of glomeruli, only PGE2 formation was found to be significantly greater in clipped kidneys. No severe damage of glomerular structure was found in the kidneys when studied by light microscopy. In additional in vivo studies, the effect of the cyclooxygenase inhibitor indomethacin on blood pressure and glomerular filtration rate (GFR) was evaluated. Following indomethacin GFR in 7 of 13 clipped kidneys of 2K,1C rats decreased from 363 +/- 77 to 188 +/- 51 microliter/100 g body wt, whereas six kidneys developed anuria. No effect of cyclooxygenase inhibition on GFR was found in N rats and in untouched kidneys of 2K,1C rats. Mean arterial blood pressure in 2K,1C hypertension fell significantly, from 158 +/- 10 to 135 +/- 7 mmHg, after cyclooxygenase inhibition. No effect was seen in N rats. The data suggest that increased glomerular PG formation in the clipped kidneys of 2K,1C rats is involved in the pathogenesis of hypertension in this animal model.

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Ethylmalonic acid (EMA) accumulation occurs in various metabolic diseases with neurological manifestation, including short acyl-CoA dehydrogenase deficiency (SCADD) and ethylmalonic encephalopathy (EE). Since pathophysiological mechanisms responsible for brain damage in these disorders are still poorly understood, we investigated the ex vivo effects of acute intrastriatal administration of EMA on important parameters of energy and redox homeostasis in striatum from young rats. We evaluated CO(2) production from glucose, glucose utilization and lactate production, as well as the activities of the citric acid cycle (CAC) enzymes, the electron transfer chain (ETC) complexes II-IV (oxidative phosphorylation, OXPHOS) and synaptic Na(+),K(+)-ATPase. We also tested the effect of EMA on malondialdehyde (MDA) levels (marker of lipid oxidation) and reduced glutathione (GSH) levels. EMA significantly reduced CO(2) production, increased glucose utilization and lactate production, and reduced the activities of citrate synthase and of complexes II and II-III of the ETC, suggesting an impairment of CAC and OXPHOS. EMA injection also reduced Na(+),K(+)-ATPase activity and GSH concentrations, whereas MDA levels were increased. Furthermore, EMA-induced diminution of Na(+),K(+)-ATPase activity and reduction of GSH levels were prevented, respectively, by the antioxidants melatonin and N-acetylcysteine, indicating that reactive species were involved in these effects. Considering the importance of CAC and ETC for energy production and Na(+),K(+)-ATPase for the maintenance of the cell membrane potential, the present data indicate that EMA compromises mitochondrial homeostasis and neurotransmission in striatum. We presume that these pathomechanisms may be involved to a certain extent in the neurological damage found in patients affected by SCADD and EE.

Hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome is an autosomal recessive disorder caused by a defect in the mitochondrial ornithine transporter, leading to accumulation of ornithine (Orn), homocitrulline (Hcit) and ammonia. Progressive neurological regression whose pathogenesis is not well established is common in this disease. The present work investigated the in vivo effects of intracerebroventricular administration of Orn and Hcit on important parameters of oxidative stress and energy metabolism in cerebral cortex from young rats. Orn and Hcit significantly increased thiobarbituric acid-reactive substances values and carbonyl formation, indicators of lipid and protein oxidative damage, respectively. Furthermore, N-acetylcysteine and the combination of the free radical scavengers ascorbic acid plus α-tocopherol attenuated the lipid oxidation and totally prevented the protein oxidative damage provoked by Orn and Hcit, suggesting that reactive species were involved in these effects. Hcit, but not Orn administration, also decreased glutathione concentrations, as well as the activity of catalase and glutathione peroxidase, indicating that Hcit provokes a reduction of brain antioxidant defenses. As regards to the parameters of energy metabolism, we verified that Orn and Hcit significantly inhibited the citric acid cycle function (inhibition of CO(2) synthesis from [1-(14)C] acetate), the aerobic glycolytic pathway (reduced CO(2) production from [U-(14)C] glucose) and complex I-III activity of the respiratory chain. Hcit also inhibited the activity of aconitase, an enzyme very susceptible to free radical attack. Taken together, our data indicate that mitochondrial homeostasis is disturbed by Orn and especially by Hcit. It is presumed that the impairment of brain bioenergetics and the oxidative damage induced by these metabolites may possibly contribute to the brain deterioration and neurological symptoms affecting patients with HHH syndrome.