Glomerular nephropathy

Fillastre JP, Mery JP, Druet P [Drug-induced glomerular nephropathies]. Nephrologie 1983 4 1-9. 

Stengel B, Cenee S, Limasset JC, Protois JC, Marcelli A, Brochard P, Hemon D. Organic solvent exposure may increase the risk of glomerular nephropathies with chronic renal failure. Int J Epidem 1995 24 427-434. 

Figure 12.1 (a) Diabetic microangiopathy pre-proliferative retinopathy, (b) Diabetic microangiopathy glomerular disruption and degeneration In diabetic nephropathy. 

Glomerular diseases (e.g., anti-glomerular basement membrane disease, focal segmental glomerularsclerosis, IgA nephropathy, hemolytic uremic syndrome, systemic lupus erythematosus, Alport s syndrome, amyloidosis, membranous nephropathy, and Goodpasture s syndrome)... 

NSAIDs can cause renal insufficiency when administered to patients whose renal function depends on prostaglandins. Patients with chronic renal insufficiency or left ventricular dysfunction, the elderly, and those receiving diuretics or drugs that interfere with the renin-angiotensin system are particularly susceptible. Decreased glomerular filtration also may cause hyperkalemia. NSAIDs rarely cause tubulointerstitial nephropathy and renal papillary necrosis. 

Renal Effects. The characteristics of early or acute lead-induced nephropathy in humans include nuclear inclusion bodies, mitochondrial changes, and cytomegaly of the proximal tubular epithelial cells dysfunction of the proximal tubules (Fanconi s syndrome) manifested as aminoaciduria, glucosuria, and phosphaturia with hypophosphatemia and increased sodium and decreased uric acid excretion. These effects appear to be reversible. Characteristics of chronic lead nephropathy include progressive interstitial fibrosis, dilation of tubules and atrophy or hyperplasia of the tubular epithelial cells, and few or no nuclear inclusion bodies, reduction in glomerular filtration rate, and azotemia. These effects are irreversible. The acute form is reported in lead-intoxicated children, whose primary exposure is via the oral route, and sometimes in lead workers. The chronic form is reported mainly in lead workers, whose primary exposure is via inhalation. Animal studies provide evidence of nephropathy similar to that which occurs in humans, particularly the acute form (see Section 2.2.3.2). 

In a study of lead workers, Wedeen et al. (1979) identified 15 who had no other risk factors for renal disease and who had previously unsuspected lead nephropathy (detected as reduced glomerular filtration... 

Most progressive nephropathies share a final common pathway to irreversible renal parenchymal damage and ESRD (Fig. 76-1). Key pathway elements are loss of nephron mass, glomerular capillary hypertension, and proteinuria. 

In mice dosed at 300 and 600 mg/kg/day, there was also an increased incidence of nephropathy (consisting primarily of degeneration of the cortical tubular epithelium with thickening of the tubular and glomerular basement membranes and increased interstitial collagen in male mice, and renal tubular regeneration in female mice). 

All hypotensive drugs lower systemic BP but, due to the specific characteristics of the glomerular capillary system, different agents may affect glomerular hemodynamics in different ways. This could be of major importance. During antihyper-tensive therapy, systemic BP may be reduced but glomerular pressure may be elevated. This may explain why the incidence of some cardiovascular complications such as stroke, has decreased, whereas the incidence of hypertensive nephropathy has remained high. 

Markowitz GS, Radhakrishnan J, Kambham N, et al Lithium nephrotoxicity a progressive combined glomerular and mbulointerstitial nephropathy. J Am Soc Nephrol 11 1439-1448,2000 Myers DH, Carter RA, Bums BH, et al A prospective study of the effects of lithium on thyroid function and on the prevalence of antithyroid antibodies. Psychol Med 15 55-61, 1985... 

ACE inhibitors have a particularly useful role in treating patients with diabetic nephropathy because they diminish proteinuria and stabilize renal function (even in the absence of lowering of blood pressure). These benefits probably result from improved intrarenal hemodynamics, with decreased glomerular efferent arteriolar resistance and a resulting reduction of intraglomerular capillary pressure. ACE inhibitors have also proved to be extremely useful in the treatment of heart failure, and after myocardial infarction (see Chapter 13 Drugs Used in Heart Failure). 

Patients with renal diseases leading to the nephrotic syndrome often present complex problems in volume management. These patients may have reduced plasma volume in conjunction with reduced plasma oncotic pressures, especially those with "minimal change" nephropathy. In these patients, diuretic use may cause further reductions in plasma volume that can impair glomerular filtration rate and may lead to orthostatic hypotension. However, most other causes of nephrotic syndrome are associated with a primary retention of salt and water by the kidney, leading to expanded plasma volume and hypertension despite the low plasma oncotic pressure. In these cases, diuretic therapy may be beneficial in controlling the volume-dependent component of hypertension. In choosing a... 

Idiopathic membranous nephropathy is the commonest form of nephrotic syndrome in middle-aged and elderly patients. The glomerular capillary wall is thickened due to immune deposits (containing mosty immunoglobulin G, IgG)... 

Size selectivity is probably caused by the mesh of glomerular basement proteins, which effectively restricts the passage of larger proteins with molecular weight of more than 150 kDa. Loss of size selectivity is probably the main cause of nonselective proteinuria in membranous nephropathy (SI3). 

Podocyte damage in membranous nephropathy is probably caused by the local activation of complement with the formation of the membranolytic complex C5b-C9. Locally formed chemotactic fragments of complement (e.g., C5a) do not penetrate through the glomerular basement membrane, and that is why in membranous nephropathy glomeruli are not infiltrated with leukocytes. 

---