Symptomatic therapy

Patients with glomerular diseases develop a wide variety of biochemical disturbances and pathophysiologic alterations leading to overt clinical manifestations. Collectively, these abnormalities give rise to the classical syndromes of glomerular disease. The clinical abnormalities resulting from these disturbances in renal pathophysiology require management in order to minimize or avoid disabling symptoms, often referred to as symptomatic therapy. This chapter provides an introduction to and overview of these abnormalities. It then covers therapies for a variety of manifestations of primary glomerular diseases, including haematuria, oedema, hypertension, hyperlipidaemia (e.g. hypercholesterolaemia), the ‘hypercoagulable’ or ‘thrombophilic’ state, non-disease-specific strategies designed to retard the progression of renal disease (loss of glomerular filtration rate, GFR), and more.

Infection-related and renal-limited glomerulonephritis

This chapter covers the infection-related glomerulonephritides, which encompass a wide swath of epidemic and endemic diseases. Bacteria, fungi, protozoa, nematodes, helminths and viruses all contribute to the glomerular disease burden. Most of these have numerous and varied extra-renal manifestations and are commonly classified as secondary glomerular diseases. However, a few have mainly or exclusively renal involvement and can be classified within the rubric of primary glomerular disease. This group of glomerular diseases is characterized by intraglomerular inflammation and cellular proliferation resulting from immunological events triggered by a variety of organisms. This chapter discusses the prototypical renal-limited forms of infection-related glomerulonephritis.

Renal-limited vasculitis (RLV)

This chapter uses the term renal-limited vasculitis (RLV) to refer to disorders of widely different aetiology and pathogenesis having in common the development of destructive lesions of the glomerular capillaries often leading to segmental necrosis of the capillary wall and proliferation of cells within Bowman’s space (crescents) in the absence of any multi-system manifestations. The resulting accumulation of cells gives rise to a ‘crescent’ enveloping the glomerular tuft itself; polymerization of fibrinogen in Bowman’s space due to passage of fibrinogen through gaps in the damaged capillary wall, the elaboration of procoagulant factors by infiltrating monocytes, and impaired fibrinolysis all contribute to its pathogenesis. Quite often the crescentic lesions are extensive and involve a majority of glomeruli. Such patients frequently manifest rapid and progressive deterioration of renal function leading to the clinical syndrome of rapidly progressive glomerulonephritis. This chapter discusses the pathology, prognosis,,treatment options, and risk factors for RLV.

The pharmacology of old and new agents for specific therapy of primary glomerular diseases

A wide variety of pharmacologic agents having diverse mechanisms of action and potential adverse events are widely used in treatment of primary glomerular diseases. However, the indications for treating specific disease entities still represent a matter of controversy and discussion among nephrologists. Indeed, randomized controlled trials are relatively few in number and are often small, underpowered, and of short duration. Conversely, drugs such as glucocorticoids (GCs) and cytotoxic agents may exert beneficial effects in some glomerular diseases, but may also be responsible for disquieting adverse events that can discourage their use in patients with indolent glomerulonephritis. Recently, a number of biological agents have been developed to spare the use of potentially toxic agents while targeting the immune cells implicated in the pathogenesis of glomerular diseases. Thus far, however, many of them have failed to find a role in the clinical management of glomerular diseases. This chapter reports the main characteristics of the pharmacological classes of immunosuppressive agents that may be used in primary glomerular diseases.

Other primary glomerular diseases

This chapter covers the other primary glomerular diseases, including their pathologies, treatment options for their management, and risk factors. Some of these primary glomerular diseases are quite rare. This chapter covers fibrillary glomerulonephritis (FGN), collagenofibrotic glomerulopathy, thin basement membrane nephropathy (TBMN), lipoprotein glomerulopathy (LPG), ‘pure’ mesangial proliferative glomerulonephritis (MesPGN), IgM nephropathy, C1q nephropathy, idiopathic nodular glomerulosclerosis, and C4 glomerulopathy. It describes the use of light microscopy, immunofluorescence, electron microscopy, and immunochemistry where applicable. For each disease, the natural history, clinical presentation, pathogenesis, and pathology are described, and, where applicable, specific studies are discussed. Any specific treatments are outlined for each.