Mechanisms of Glomerular Injury and ChronicKidneyDisease
Neoplasms of the Kidney
The kidney is a structurally complex organ that has evolved to carry out a number of important functions: excretion of the waste products of metabolism, regulation of body water and salt, maintenance of acid balance, and secretion of a variety of hormones and prostaglandins. Diseases of the kidney are as complex as its structure, but their study is facilitated by dividing them into those that affect its four components: glomeruli, tubules, interstitium, and blood vessels. This traditional approach is useful because the early manifestations of diseases that affect each of these compartments tend to be distinctive. Furthermore, some structures seem to be more vulnerable to specific forms of renal injury; for example, glomerular diseases are often immunologically mediated, whereas tubular and interstitial disorders are more likely to be caused by toxic or infectious agents. However, some disorders affect more than one structure, and functional interdependence of structures in the kidney means that damage to one component almost always affects the others. Thus, severe glomerular damage impairs blood flow through the peritubular vascular system; conversely, tubular destruction, by increasing intraglomerular pressure and inducing the production of cytokines and chemokines, may lead to glomerular sclerosis. When chronic kidney disease progresses to its most advanced stage, so-called end-stage renal disease, all four compartments of the kidney are usually damaged. Due to the large functional reserve capacity of the kidney, early signs of kidney disease are often missed, and much renal damage may occur before renal dysfunction becomes clinically apparent. Before discussing individual diseases of the kidney, we describe clinical manifestations of kidney diseases shared by several disorders.
The clinical manifestations of renal disease can be grouped into reasonably well-defined syndromes. Some are peculiar to glomerular diseases, and others are shared by several renal disorders. Before we list the syndromes, a few terms must be defined.
Azotemia is an elevation of blood urea nitrogen and creatinine levels and usually reflects a decreased glomerular filtration rate (GFR). GFR may be decreased as a consequence of intrinsic renal disease or extra-renal causes. Prerenal azotemia is encountered when there is hypoperfusion of the kidneys (usually due to reduced extracellular fluid volume). This decreases GFR in the absence of renal parenchymal damage and is usually reversible if the hypoperfusion is corrected in time. Postrenal azotemia results when urine outflow is obstructed. Relief of the obstruction is followed by correction of the azotemia.
When azotemia gives rise to clinical manifestations and systemic biochemical abnormalities, it is termed uremia. Uremia is characterized not only by failure of renal excretory function but also by a host of metabolic and endocrine alterations incident to renal damage. In addition, there is secondary gastrointestinal (e.g., uremic gastroenteritis); neuromuscular (e.g., peripheral http://ebooksmedicine.net neuropathy); and cardiovascular (e.g., uremic fibrinous pericarditis) involvement.
Below is a brief summary of the various clinical manifestations and syndromes of renal diseases with their defining features. The two most common syndromes associated with glomerular diseases, nephrotic and nephritic, are discussed in detail.
Nephrotic syndrome is characterized by the following:
Proteinuria, with daily protein loss in the urine of 3.5 g or more in adults (said to be in the “nephrotic range”)
Hypoalbuminemia, with plasma albumin levels less than 3 g/dL
Generalized edema, the most obvious clinical manifestation