Glomerular disease and nephrotic syndrome

The sieve that fails in glomerular disease is not one membrane but three layers working together. The endothelial cells lining the capillary are fenestrated, perforated by small pores that let plasma through while repelling cells. Around them lies the glomerular basement membrane, a gel of collagen and glycoproteins carrying a strong negative charge that repels negatively charged albumin. Outside it sit the podocytes, star-shaped epithelial cells whose interlocking foot processes are bridged by the slit diaphragm, a molecular zip that forms the final size-selective barrier. A protein leak means the podocyte layer has failed, most often because the foot processes have been flattened in a change called effacement that is visible only on electron microscopy.

The inflammation of the nephritic picture is an immune event with a recognisable sequence. Antigens — streptococcal proteins, hepatitis B or C antigens, or the body’s own basement membrane — meet antibodies either in the circulation or inside the capillary wall. The resulting immune complexes deposit in the wall, activate complement, and release C5a, which attracts neutrophils. Those neutrophils discharge proteases and oxygen radicals that digest the basement membrane, so red cells escape into the filtrate. On immunofluorescence the deposits look granular, a pattern that distinguishes them from the smooth linear staining of anti-glomerular-basement-membrane disease such as Goodpasture syndrome. In post-streptococcal disease the electron microscope shows discrete subepithelial humps where the complexes have lodged, and the latency of one to two weeks after a throat infection, or three to six weeks after a skin infection, is exactly the time the immune response needs to build those deposits. If the injury is severe, mesangial cells and parietal epithelium proliferate and form crescents that fill Bowman’s space and obstruct filtration, which is why creatinine can rise quickly and why a biopsy is taken.

The nephrotic picture damages the podocyte rather than the whole wall. In minimal change disease, the commonest cause in children, the foot processes efface but light microscopy looks almost normal, so the diagnosis is made by electron microscopy and the syndrome usually responds to corticosteroids. In membranous nephropathy the deposits sit on the subepithelial side and thicken the basement membrane over months, producing the classic adult nephrotic picture. Because there is no neutrophil-driven breach of the membrane, these patients pass protein but rarely blood, which is the practical difference the nurse sees on the dipstick and in the urine colour.

Once the glomerulus leaks more than about 3.5 g of protein a day, the loss stops being a urinary curiosity and becomes a whole-body disease. Albumin is the main determinant of plasma oncotic pressure, the force that holds water inside the capillaries. As serum albumin falls below roughly 30 g/L, that force weakens, fluid moves into the interstitium, and the patient develops the sequence clinicians look for: periorbital puffiness on waking, then ankle swelling, then ascites and sometimes a pleural effusion. The liver senses the fall and responds by manufacturing more protein, but it also manufactures lipoproteins, which is why cholesterol and low-density lipoprotein rise. This secondary hyperlipidaemia is not harmless; it adds long-term cardiovascular risk and is why lipid-lowering drugs are part of the plan. Two less obvious dangers follow from the same loss. Immunoglobulins and complement factors are proteins too, so a nephrotic patient loses part of the defence against encapsulated bacteria; pneumococcal peritonitis is a classic complication in nephrotic children, and any fever deserves attention. Antithrombin III is also lost, while the liver simultaneously raises fibrinogen, so the blood becomes hypercoagulable and thromboses form, particularly in the renal vein but also in the legs and lungs. Renal vein thrombosis can present simply as worsening proteinuria and flank pain, which is why a sudden deterioration is not assumed to be a relapse. Finally, the skin of an oedematous patient is under mechanical strain. The tissue is stretched, its perfusion is poor, and it breaks down under quite modest pressure, so a sacral or heel pressure injury can develop within hours. Every gram of retained fluid also means weight gain, and the nurse measures it rather than waiting to see the swelling. Protecting anasarcous skin — repositioning, offloading, careful washing and drying, no vigorous massage — is as much a part of nephrotic care as any prescription.

Because glomerular disease is often silent between relapses, the nurse’s measurements are the disease’s early warning system. Urinalysis is the first test: a dipstick detects protein, and microscopy identifies red cells, white cells and casts. A cast is a cylindrical mould of the tubule lumen, formed when a protein called uromodulin gels and traps whatever cells are present; a red cell cast therefore proves that bleeding is glomerular rather than from the bladder or the urethra. Quantifying the leak matters more than detecting it, so a 24-hour collection or a protein-to-creatinine ratio on a single specimen is used, and a value above 3.5 g per day defines nephrotic-range proteinuria. Serum albumin, creatinine, urea, potassium, bicarbonate, calcium and phosphate complete the picture of what the failing filter is doing to the rest of the body.

Kidney biopsy is the definitive test, and it turns a syndrome into a named diagnosis with a treatment. The nurse prepares the patient — coagulation screen, consent, blood pressure, intravenous access — and after the procedure enforces a period lying flat, watches the puncture site and the urine for bleeding, monitors pulse and blood pressure for haemorrhage, and delays heavy lifting. Because the kidney clears many drugs, doses are reviewed; non-steroidal anti-inflammatory drugs and iodinated contrast media are avoided because they are nephrotoxic, and potassium-sparing drugs or supplements are questioned in a patient who may already retain potassium.

Teaching is the last intervention and the one that prevents readmission. Nephrotic patients on corticosteroids need to know why the dose is not stopped suddenly, how to recognise weight gain, infection and mood change, and why immunisation against pneumococcus and influenza matters. Patients are told to report a fever, a sudden rise in weight, foamier urine, or reduced urine output at once rather than waiting for the next appointment. Diet advice is concrete: sodium restriction when blood pressure or oedema demands it, protein of high biological value in measured amounts with enough calories to spare it, and caution with salt substitutes that contain potassium.