bubble_chart Overview

Minimal change nephropathy, also known as lipoid nephrosis, is one of the most common diseases causing nephrotic syndrome. It accounts for approximately 75% of primary nephrotic syndrome in children and about 70-80% of nephrotic syndrome in children under 8 years old. It is also not uncommon in adults, making up 15-20% of primary nephrotic syndrome cases in patients over 16 years old.

bubble_chart Pathogenesis

The pathogenesis of minimal change nephropathy remains unclear, characterized by the loss of negative charge in the glomerular capillary walls. This condition can also occur in transplanted kidneys, supporting the notion that circulating humoral factors may deplete the glomerular negative charge. These factors impair the glomerular charge barrier, leading to selective proteinuria. Additionally, in cases of minimal change nephropathy associated with Hodgkin's disease, responses to steroids and alkylating agents are observed, with rapid remission of nephropathy following removal of affected lymph nodes. Some patients experience disease remission after viral infections such as measles, suggesting abnormal T-lymphocyte function and the production of certain lymphokines that increase glomerular capillary wall permeability. However, the specific substance involved has not yet been definitively identified.

bubble_chart Pathological Changes

Under light microscopy, the glomeruli appear essentially normal. Immunofluorescence examination generally shows no immune deposits, while the typical lesion under electron microscopy is the diffuse effacement or fusion of epithelial foot processes. Occasionally, focal electron-dense deposits may be observed in the mesangial region. Minimal change nephropathy may also exhibit morphological abnormalities, such as mild, grade II focal or diffuse mesangial cell proliferation and focal glomerulosclerosis. Some authors suggest that such cases should be classified as a distinct glomerular disease, while others propose that minimal change nephropathy, mesangial proliferative glomerulonephritis, and focal glomerulosclerosis represent three different pathological stages of the same disease, though this requires further in-depth research. However, the focal sclerotic lesions that appear in the late stage (third stage) of minimal change nephropathy can serve as a histological marker indicating a more severe condition and poor response to steroid therapy. In some cases of minimal change nephropathy, immunofluorescence may reveal mild deposits of IgM, IgA, or C₃

in the mesangial region. The simultaneous presence of mesangial cell proliferation and IgM deposits often suggests poor or delayed response to steroid therapy and an increased likelihood of disease progression. Some authors classify these patients as having distinct diseases, such as mesangial proliferative nephritis or IgM nephropathy.

bubble_chart Clinical Manifestations

The peak age for children is between 2 and 6 years old. In adults, the condition is most common between 30 and 40 years old, and the incidence of minimal change disease is also high among nephrotic syndrome patients over 60 years old. Among children, males are twice as likely as females to be affected, while in adults, the gender ratio is roughly equal. About one-third of patients may have an upper respiratory or other infection prior to the onset of the disease. The onset is mostly acute, with the typical first symptom being overt nephrotic syndrome, accounting for 90% of childhood nephrotic syndrome cases and 20% of adult cases. Blood pressure is normal. Microscopic hematuria is observed in 20% of patients, and its incidence increases with age, particularly in patients over 60 years old, where interstitial inflammation, fibrosis, and vascular lesions lead to a higher rate of microscopic hematuria. However, gross hematuria is rare. Due to hypovolemia and decreased renal perfusion, about one-third of patients may exhibit reduced glomerular filtration rate (GFR) at initial diagnosis. Urine sediment examination shows no cells or casts. In severe cases, 24-hour urine protein may exceed 40g. In children, the proteinuria is typically highly selective, mainly consisting of albumin and very small amounts of high-molecular-weight proteins such as IgG, α_2-

macroglobulin, and C₃. In adults, the presentation varies; minimal change disease in elderly patients over 60 may manifest as non-selective proteinuria, often accompanied by hypertension and reduced GFR. Recent studies have found that transferrin, with a molecular weight of 88,000, due to its spherical structure, also enters the tubular fluid along with albumin. In urine with a pH of 4.5–5.5, iron from transferrin is released into the tubular fluid, where Fe³⁺ can generate numerous oxygen-free radicals, injuring the renal interstitium and tubules. Additionally, Fe³⁺ can directly damage the tubules and interstitium. No fibrin degradation products or C₃ are found in the urine. Blood complement levels are normal, though C_1q may show grade I reduction. During the attack stage, IgG levels are generally very low, while IgM levels are grade I elevated in both the attack and remission stages. The histocompatibility antigen HLA-B₁₂ is significantly more common in minimal change disease, suggesting a possible genetic link. Anti-streptolysin O (ASO) antibody titers are often markedly reduced. Minimal change disease should be carefully differentiated from concurrent Hodgkin's disease. Additionally, nephrotic syndrome caused by nonsteroidal anti-inflammatory drug (NSAID) allergy may histologically resemble minimal change disease but is usually accompanied by interstitial nephritis and renal dysfunction.

In rare cases, acute renal failure can occur without obvious hypovolemia. Prerenal azotemia caused by decreased blood colloid osmotic pressure due to hypoproteinemia and severe blood volume depletion is seen in only 7-38% of patients. If there are no typical clinical manifestations of hypovolemia, accompanied by decreased urine concentration function and increased urinary sodium excretion—especially if urine output does not increase after administration of plasma products or albumin—renal acute renal failure should be considered. In such cases, in addition to drug-induced acute tubular necrosis (nephrotoxic drugs such as aminoglycosides like gentamicin) or acute interstitial nephritis (antibiotics, nonsteroidal anti-inflammatory drugs, etc.), another special type of acute renal failure should also be recognized. The underlying glomerular disease in nephrotic syndrome with idiopathic oliguric acute renal failure is often minimal change disease or grade I mesangial proliferative GN. It is more common in older patients with severe nephrotic syndrome, elevated blood pressure (especially systolic) accompanied by vascular sclerosis. Pathological changes, apart from those of minimal change disease, include flattened proximal tubular epithelial cells, loss of brush borders, and/or interstitial edema, but without typical tubular necrosis or interstitial nephritis lesions. Since the pathological changes in minimal change disease complicated by acute renal failure are relatively mild and mostly reversible, it is primarily a hemodynamic disorder. Although blood volume and renal blood flow are roughly normal, the glomerular filtration rate (GFR) transiently decreases, leading to a reduced filtration fraction (FF). The two components of single-nephron GFR show significant changes: the ultrafiltration coefficient decreases by more than 50%, and due to decreased intravascular colloid osmotic pressure, the net ultrafiltration pressure (net driving force, i.e., transcapillary hydrostatic pressure ΔP minus the colloid osmotic pressure difference Δπ) increases, exacerbating renal interstitial edema.

bubble_chart Treatment Measures

Before the application of hormones and modern antibiotics, the spontaneous remission rate was estimated to be 25-40%. Due to infectious and embolic complications, the 5-year mortality rate for pediatric patients at that time exceeded 50%, but currently it is approximately 7-12%; in children sensitive to hormone therapy, it is less than 2%.

The conventional dose of hormone therapy for children is prednisone 60mg/m² per day, and for adults, prednisone 40-60mg/day, followed by gradual tapering over 4-6 months. 90% of children respond within 4 weeks, and 90% of adults respond within 8 weeks. If significant proteinuria persists after treatment, immunosuppressants should be added.

Among those sensitive to hormones, approximately 50% can maintain negative urine protein or relapse after dose reduction or discontinuation, but most patients eventually achieve remission. The other 50% experience frequent relapses or become hormone-dependent (meaning larger doses of hormones are needed to control proteinuria), often accompanied by hormone-related side effects, which are more pronounced in pediatric patients. Adding cyclophosphamide 2-3mg/kg per day (75mg/m² per day for children) for 8-12 weeks can prolong the stage of remission for hormone-sensitive patients. Due to the gonadotoxicity, teratogenic effects, and other toxic reactions of cytotoxic drugs, they are only used when both nephropathy and hormone side effects are severe. For patients who respond to hormones but experience repeated relapses or hormone dependence, and for whom cytotoxic agents like cyclophosphamide are not indicated, cyclosporine A can be used at 3.5-4mg/(kg·d) orally. After 4 months, most patients with minimal change nephropathy achieve complete remission of nephrotic syndrome, significantly reducing the hormone dose.

If nephrotic syndrome caused by minimal change nephropathy does not respond to the above aggressive treatments, the following conditions must be considered: ① Control or eliminate internal infections, particularly hidden foci of infection. ② Renal vein thrombosis. Prompt CT examination should be performed. If renal vein thrombosis is confirmed, systemic administration of urokinase 40,000-80,000 units/day, diluted in 40ml of 0.9% sodium chloride, can be given intravenously once or twice daily. Alternatively, femoral artery puncture and catheterization can be performed to infuse urokinase into the affected renal artery over 1 hour, with a total dose of 200,000 units, followed by oral dipyridamole 25mg three times daily and warfarin 2.5mg once daily. CT re-examination after one month shows a 100% efficacy rate, and long-term follow-up over 5 years confirms the effectiveness of this treatment. We believe that early diagnosis of renal vein thrombosis and aggressive anticoagulant therapy can improve the prognosis of primary glomerulopathy and various primary glomerulonephritis, maintaining normal renal function. ③ Most patients who are insensitive to hormones have focal glomerulosclerosis. ④ To reduce the relapse rate after discontinuing hormones, cortisol levels should be measured before stopping hormone therapy. Patients with normal cortisol levels are less likely to relapse after discontinuation.