There are relatively a low number of pathologic patterns of renal lesion that are consequence of an immense amount of etiologic factors: several diseases or factors can produce a same histologic type of injury, and in the same way: a disease or etiologic factor can produce several types of morphologic changes. Also, there are a limited number of clinical manifestations for a great number of renal diseases. This variability depends on the type of injury and its location, on the host response, and, logically, on the etiologic agent.

Renal diseases can be classified according to clinical manifestations, etiology, immunopathology and morphologic alterations that produce.

Based on the clinical manifestations several clinical syndromes have been defined:

Nephritic syndrome: Decreased glomerular filtration rate (evidenced by elevated creatinine or BUN or decreased creatinine clearance), hematuria, edema, mild proteinuria, and hypertension (in many cases there is oliguria)

Nephrotic syndrome: Massive proteinuria (>3.5 gr/24 hours for adults or >40 mg/m2/hour in children), hypoalbuminemia, edema and hyperlipidemia; although massive proteinuria has finished being the most important factor for the diagnosis of the syndrome because it indicates serious renal disease.

Acute renal failure: Rapid decline in glomerular filtration rate (hours to days), retention of nitrogenous waste products, and perturbation of extracellular fluid volume and electrolyte and acid-base homeostasis. It can be, or no, associates to oliguria, and is often reversible.

Rapidly progressive glomerulonephritis: Subacute renal failure over weeks to months, active urine sediment, variable amount of hypertension, edema, oliguria, and proteinuria.

Chronic renal failure: Chronic renal disease is a pathophysiologic process resulting in the inexorable attrition of nephron number and function and frequently leading to end-stage renal disease: a clinical state or condition in which there are an irreversible loss of renal function, of a degree sufficient to render the patient permanently dependent upon renal replacement therapy (dialysis or transplantation). Uremia is the clinical and laboratory syndrome, reflecting dysfunction of all organ systems as a result of untreated or undertreated acute or chronic renal failure.

The glomerular pathologic changes can produce any type of clinical syndrome, but, in general, some patterns of renal changes are associated to certain syndromes:

Membranous GN, Focal segmental glomeruloesclerosis, minimal change disease are associated with nephrotic syndrome.

Diffuse proliferative endocapillary GN (frequently postinfectious) and membranoproliferative GN are associated to nephritic syndrome.

IgA nephropathy, Alport syndrome, and thin basement membrane disease can appear as isolated hematuria, some times with proteinuria, usually in non-nephrotic range.

The systemic diseases affecting the kidney have still more variability in their clinical expression.

Let us remember, again, that a type of glomerular lesion can appear clinically different in different patients.

The clinicopathologic correlation is of great importance to arrive to the correct diagnosis. A final diagnosis must never be done without the complete clinical information. In addition, in all the GN cases must have, at least, immunopathologic study (immunofluorescence or immunoperoxidase), to detect immune deposits, and many cases also require ultrastructural study (electron microscopy).

When evaluating a renal biopsy we must, initially, determine which of the four histologic compartments (glomeruli, interstitium, tubules and vessels) is/are the most comprised for the disease. If we began evaluating the glomeruli, we must see cellularity degree. It must not have more than three nuclei in each mesangial area, i.e. the mesangium among several capillaries, surrounded by them (must be distinguished from the lobes: in each lobe there are several mesangial areas - see Histology). Hypercellularity must be evaluated in thin sections: no more than 2 - 3 microns thickness; one of the main “causes” of hypercellularity is a tick section: false hypercellularity. Do not evaluate the cellularity in the mesangial areas adjacent to the vascular pole because in them there are more cells.

The second step is to determine the type of hypercellularity:

Mesangial: Proliferating cells are located in the mesangium, with nothing or little diminution of the capillary lumens. The nuclei usually have a relatively homogenous aspect because proliferating cells are all, or almost all, from similar origin: mesangials.

Endocapillary: In this type of injury the proliferation is not only located into capillary lumens, but the cellular proliferation occupy the glomerular tuft and compress capillaries. The proliferating cells are from diverse origin: endothelial, mesangial, and inflammatory (lymphocytes, monocytes, and neutrophils), nevertheless, it is called “endocapillry” by convention (hypercellularity within the capillary tuft). The nuclei of the cells are more variable in form and size (because there are several types of cells) and tend to obstruct the capillary lumen. The proliferation is not limited to the mesangium. It can be global or segmental.

Extracapillary (crescents): Proliferation of cells in the Bowman’s space, with at least two layers of cells covering Bowman’s capsule. The cells that proliferate are parietal epithelial and infiltrating inflammatory cells, mainly monocytes. This type of proliferation is also known as: crescents. It can be circumscribed or circumferential.

When there is endocapillary and/or extracapillary cell proliferation we say that there is a “true glomerulonephritis”.

Other important terms in the description of glomerular changes:

Global: A lesion involving the entire glomerulus.

Segmental: A lesion involving a part of the glomerulus, with al least a segment spared.

Diffuse: A lesion involving all or most of the glomeruli.

Focal: A lesion involving only some glomeruli. An exact number (or percentage) is not defined and accepted by all authors. For some it is <80% of glomeruli. In some classifications, like lupus nephritis, is called diffuse when there are 50% or more of glomeruli involved and focal if <50%.

Hyalinosis: Homogenous, amorphous glomerular deposits composed mainly of proteinaceous material. It is observed reddish, or green or sometimes blue, according to the technique, with the trichrome stain, and they are positive with the PAS (periodic acid of Schiff) stain. Similar lesions can be observed in arterioles: hyalin arterioloesclerosis. It must be differentiated from fibrinoid necrosis, that displays similar colour with these stains, but it is a more granular material, less homogenous and is accompanied by cellular detritus and/or inflammatory cells.

Sclerosis: Is a glomerular scar produced with proliferation of type IV collagen (glomerular collagen).

Fibrosis: Scar produced with predominantly type I collagen (interstitial type collagen).