Neutrophil gelatinase-associated lipocalin (NGAL) as a biomarker of kidney damage: a review / Lipocalina associada à gelatinase neutrofílica (NGAL) como um biomarcador de lesão renal: uma revisão

Neutrophil gelatinase- associated lipocalin (NGAL) is a protein molecule predominantly expressed in the distal nephron after the occurrence of renal injury. Unlike the serum creatinine and the glomerular filtration rate, which are the renal function markers, the increased levels of NGAL, both in serum and urine, are closely linked to the structural injury to the nephron. Clinical studies indicate that a few hours after the occurrence of acute renal injury, the serum and urinary levels of NGAL are already significantly elevated, while the serum creatinine levels and renal clearance only undergo significant changes between 24-48h after injury. Thus, the use of renal function markers, usually assessed in the clinical practice, they may have some limitations also hindering the implementation of early measures aimed at protecting the kidneys. This literature review aims at examining the biological aspects and the applications of NGAL measurement in some clinical conditions, including kidney failure, kidney diseases and renal ischemia.

Lipocalina associada à gelatinase neutrofílica (NGAL) é uma molécula proteica predominantemente expressa na parte distal do néfron após a ocorrência de lesão renal. Diferentemente da creatinina sérica e da taxa de filtração glomerular, que são marcadores de função renal, os níveis aumentados de NGAL, tanto no soro quanto na urina, estão intimamente ligados a lesões estruturais do néfron. Os estudos clínicos indicam que poucas horas após a ocorrência da lesão renal aguda os níveis séricos e urinários de NGAL já se apresentam significativamente elevados, enquanto os níveis séricos de creatinina e a sua depuração renal apenas sofrem alterações significativas entre 24-48h após a lesão. Assim, a utilização de marcadores de função renal, usualmente avaliados na prática clínica, pode apresentar algumas limitações além de dificultar a aplicação de medidas precoces que visam a proteção renal. Esta revisão da literatura tem por objetivo analisar os aspectos biológicos e as aplicações da mensuração de NGAL em algumas condições clínicas, incluindo injúria renal, nefropatias e isquemia renal.

The role of the distal nephron in the regulation of acid-base equilibrium by the kidney

The present paper reviews mechanisms by which the kidney controls systemic acid-base balance, with emphasis on the role of the distal nephron, and particularly of the cortical distal tubule. These mechanisms are essentially based on H-ion transport along the whole nephron. In proximal tubule cells, approximately 80 of H-ion secretion is mediated by Na+/H+ exchange, and 20 by H(+)-ATPase. In the distal nephron, acid-base transport mechanisms are located mainly in intercalated cells. H-ion secretion is effected by vacuolar H(+)-ATPase in alpha-intercalated cells and, in K-depleted animals, also by the gastric type H/K ATPase. In animals in alkalosis, beta-intercalated cells secrete bicarbonate by an apical Cl-/HCO3- exchanger, while a basolateral H-ATPase transfers H-ions into the interstitium. In cortical distal tubule, these mechanisms have been shown to be present in the intercalated cells of the connecting segment and of the initial collecting duct (the late distal tubule of micropuncture experiments). In the convoluted distal tubule (early distal tubule), most H-ion secretion occurs by means of the Na+/H+ exchanger. These data show that the distal nephron, including the cortical distal tubule, is a nephron segment responsible for a sizeable portion of bicarbonate reabsorption and titratable acid generation, as well as for bicarbonate secretion under appropriate metabolic conditions, being therefore the site of fine regulation of renal mechanisms that maintain acid-base homeostasis.

Alguns fatores na progressäo da doença renal / Some factors in evolution of chronic renal failure

Adaptaçöes estruturais e funcionais foram demonstradas em néfrons remanescentes após lesäo renal. O grau destas adaptaçöes correlaciona-se diretamente com a quantidade de parênquima renal perdido. No entanto, várias observaçöes sugerem que a evoluçäo para insuficiência renal crônica (IRC), após esta perda de massa renal funcionante, é progressiva. Porém, os fatores responsáveis por esta evoluçäo ainda näo estäo estabelecidos. A hipertensäo e o hiperfluxo glomerulares que ocorrem nos néfrons remanescentes, especialmente em pacientes ou animais alimentados com dieta hiperprotéica, foram identificados como fatores que aceleram esta evoluçäo. Sabe-se também que as prostaglandinas (PGs) vasodilatadoras encontram-se elevadas na urina de humanos e animais de experimentaçäo com IRC, e que participam da manutençäo da filtraçäo glomerular. Alguns estudos recentes têm sugerido que estas PGs exercem um papel fundamental na manutençäo da vasodilataçäo renal que ocorre nos néfrons remanescentes. Sugere-se que as PGs teriam um papel fundamental na evoluçäo da IRC paralelamente com a dieta hiperprotéica. Finalmente, mecanismos hemodinâmicos da progressäo da IRC säo sugeridos e possivelmente novos enfoques terapêuticos conservadores (näo dialíticos) deveräo ser indicados

Steady state behaviour of the ascending limb of Henle's loop in a nephron below the juxta-medullary apparatus

The nature of many kidney diseases is still unknown and so the therapy. The reasons for such uncertainty are numerous but, the most important is the great difficulty to study events successfully in the cellular level and the inaccurate results for experiments obtained at such level. So many of the phenomena which cause disease are still unknown and subsequently they are the subject of many contradicting theories. The strong tools of modeling is now adapted to predict concentration profile along the ascending limb of Henle. The reason for such a choice lies in its difference from that of the descending limbs as being performing active transport and satisfying requirements of modeling. It is greatly similar to plug flow reactor in nature

Towards substantiation of intact nephron hypothesis.

A prolonged study on sheep and goats; whose 83% of total renal mass was removed, revealed that even an extremely heterogenous kidney not only performed the regular function but remained responsive for the demands of the body.