Title All Urinary Disorders.pdf ✅

Glomerular diseases • 397 15 Most types of glomerulonephritis are immunologically mediated and several respond to immunosuppressive drugs. Deposition of antibody occurs in many types of glomerulonephritis and testing for circulating or glomerular deposition of antibodies may aid diagnosis (see Fig. 15.11 and Boxes 15.8 and 15.10). In small-vessel vasculitis, no glomerular antibody deposition is observed (pauci-immune), but the antibodies may be indirectly pathogenic by activating neutrophils to promote endothelial injury (Fig. 15.11). Glomerulonephritis is generally classified in terms of the histopathological appearances, as summarised in Box 15.15 and Figure 15.12. Many non-specialists find the terminology used in describing glomerulonephritis to be confusing; some definitions are provided in Box 15.16. It is important to stress that the histological appearance rarely confirms a specific renal disease but rather suggests a limited range of diagnoses, which may be confirmed by further investigation. Conversely, some diseases, such as lupus, are associated with more than one histological pattern of injury. The most common histological subtypes may be categorised according to their typical clinical presentation, as discussed below. Genetic disorders associated with glomerular disease are described later (p. 403). pathological cause. Investigation and management of suspected diabetes insipidus are described on page 688. Nocturia Nocturia is defined as waking up at night to void urine. It may be a consequence of polyuria but may also result from increased fluid intake or diuretic use in the late evening (including caffeine). Nocturia also occurs in CKD, and in prostatic enlargement when it is associated with poor stream, hesitancy, incomplete bladder emptying, terminal dribbling and urinary frequency due to partial urethral obstruction (p. 437). Nocturia may also occur due to sleep disturbance without any functional abnormalities of the urinary tract. Urinary incontinence Urinary incontinence is defined as any involuntary leakage of urine. It may occur in patients with a normal urinary tract, as the result of dementia or poor mobility, or transiently during an acute illness or hospitalisation, especially in older people (see Box 15.54, p. 436). The pathophysiology, investigation and management of urinary incontinence are discussed in detail later in the chapter (p. 436). Glomerular diseases Glomerular diseases account for a significant proportion of acute and chronic kidney disease. Most patients with glomerular disease do not present acutely and are asymptomatic until abnormalities are detected on routine screening of blood or urine samples. There are many causes of glomerular damage, including immunological injury, inherited diseases such as Alport’s syndrome (p. 403), metabolic diseases such as diabetes mellitus (p. 757), and deposition of abnormal proteins such as amyloid in the glomeruli (p. 81). The glomerular cell types that may be the target of injury are shown in Figure 15.11. Proteinuria is the hallmark of glomerular disease; however, the response of the glomerulus to injury and hence the predominant clinical features vary according to the nature of the insult, ranging from fulminant nephrotic syndrome to rapidly progressive glomerulonephritis (see Fig. 15.9). Several prognostic indicators are common to all causes of glomerulonephritis (Box 15.14) and may be helpful in assessing the need for immunosuppressive therapy. Glomerulonephritis While glomerulonephritis literally means ‘inflammation of glomeruli’, the term is often used more broadly to describe all types of glomerular disease, even though some of these (e.g. minimal change nephropathy) are not associated with inflammation. Fig. 15.11 Glomerulonephritis associated with antibody production. Antibodies and antigen–antibody (immune) complexes may target or be deposited in specific components of the glomerulus, resulting in different patterns of histological injury and clinical presentation. Testing for antibody deposition in the glomerulus by immunofluorescence (IF) on renal biopsy tissue or for antibodies in the serum may aid diagnosis. Diagnostic tests are shown in italics. (ANA = antinuclear antibody; ANCA = antineutrophil cytoplasmic antibody; dsDNA = double-stranded DNA; GBM = glomerular basement membrane; IgA = immunoglobulin A; SLE = systemic lupus erythematosus) Endothelium (indirectly) Small-vessel vasculitis ANCA (serum) GBM Goodpasture's disease Anti-GBM antibody (serum + IF on biopsy; see Fig.15.12H) Podocyte Membranous nephropathy Anti-phosphilipase A2 receptor 1 (serum + IF on biopsy; experimental at present; see Fig.15.12F) Planted antigens SLE – ANA, anti-dsDNA (serum) Post-infectious glomerulonephritis Circulating immune complexes Cryoglobulinaemia (Cryoglobulins in serum) Serum sickness Endocarditis Mesangium IgA nephropathy (polyclonal rise in serum IgA in 50% patients; IF on biopsy; see Fig.15.12G) 15.14 Poor prognostic indicators in glomerular disease • Male sex • Hypertension • Persistent and severe proteinuria • Elevated creatinine at time of presentation • Rapid rate of decline in renal function • Tubulo-interstitial fibrosis observed on renal biopsy