Minimal Change Disease

Definition Of Minimal Change Disease

• Minimal Change Disease is also called lipid nephrosis or minimal lesion disease.
  • Excrete lipid globules or fat globules in the urine
    • So-called lipid nephrosis
• There are subtle changes in the microscopy and effacement of podocytes in electron microscopy called minimal lesions.
• The Light microscopy and immunofluorescence will be absolutely normal.

Epidemiology Of Minimal Change Disease

• There are Seasonal changes observed in Minimal Change Disease.
  • Increases in winter and not much difference in summer
• In children, male children have a higher probability of acquiring the disease than female Children
• In adults, both males and females have equal predisposition 

Pathogenesis Of Minimal Change Disease

• T cell-mediated mechanism
  • No antibodies detected against minimal change disease
  • There are multiple active cytokines 
  • Good response to corticosteroids 
  • When children develop measles, during their recovery who want to recover from measles also recover from minimal change in disease.
    • T cell immunity suppress
• Circulating factors
  • Cytokines- IL-8, IL-13
    • The mechanism is not well established 
  • Hemopexin
    • It is synthesized in the liver.
    • It goes to the glomerular basement membrane to attack the heparan sulfate - causing proteinuria. 
    • Hemopexin does not cause selective proteinuria
    • Not highly recommended 
  • Microbial products
    • Microbial products bind to TLR3,4 and increase CDAT
    • Binds and Inhibits the phosphorylation of nephrin.
    • The interdigitated podocyte, which maintains the space, is lost
    • Podocyte collapse happens, leading to effacement 
    • Whenever a child gets URI because of a viral infection 
    • They go back into relapse

Mechanism of Proteinuria In Minimal Change Disease

• Loss of anionic changes in the glomerular filtration barrier 
• Podocyte dysfunction 
  • CD80
    • Antigen-presenting cell expressing CD80
    • Viral infection 
      • Stimulation of TLR3 podocyte receptors
      • Overexpression of CD80
      • Inadequate CTLA4 response
      • Interference with phosphorylation of nephrin
      • Affects barrier
• Angptl- 4- overexpression 
  • Comes to the glomerular basement membrane 
  • Goes and binds to the heparan sulfate proteoglycans
    • Causes the negative charge 
    • Loss of negative charge 
    • Negative charges are filtered against the glomerular basement membrane 

Pathology Of Minimal Change Disease

• Light microscopy 
  • Slight increase in mesangial matrix and hypercellularity
  • Global Glomerulosclerosis
    • <10%
  • Segmental Glomerulosclerosis indicates FSGS
  • Minor IFTA
    • Interstitial fibrosis and tubular atrophy 
  • Fat and hyaline droplets in the Proximal tubule
    • Reabsorbed ones
• Immunofluorescence 
  • IgM nephropathy
    • Increased proteinuria and poor prognosis 
    • Less response to steroid 
  • C1q nephropathy
    • Poor prognosis 
    • The response may not be adequate 

• Electron microscopy 
  • Podocyte is on GBM
  • It has space
  • Podocyte is effaced - thinned out and flat
  • Not much space - Interdigitation is happening 

Clinical Features Of Minimal Change Disease

• Edema 
  • Only after 5-7% of the increase in body weight happens 
  • Seen in legs and peri-orbital region
  • Heart failure patients can’t lie down
    • Due to orthopnea 
    • Edema collects more in the downward area 
  • Renal issues
    • Edema occurs in the face after sleeping
  • Edema can also happen in the bowel
    • The patient can present with diarrhea 
• Blood pressure 
  • Normal
  • Hypertension 
    • Relapse
      • Volume depletion
      • Renin-angiotensin activation leads to hypertension 
      • Once we infuse albumin, restore the volume of the patient to settle hypertension 
• Renal vein thrombosis 
• Abdominal pain, nausea
  • Bowel edema
• Muehrecke’s nail
  • A transient white band seen in the nail of a child or adult with nephrotic syndrome
    • Indicates release 
    • Hypoalbuminemia
• Xanthoma, xanthelasma is seen due to hyperlipidemia
• Macroscopic hematuria 
  • Rare event 
  • Suspect renal vein thrombosis 

Laboratory Findings Of Minimal Change Disease

• Proteinuria
  • Selective: loss of albumin 
  • Adult: >3.5g in 24 hrs
  • Children: 500mg/kg/24 hrs, 40mg/h/m2, 200mg protein/ mmol of creatinine
  • Urine routine
    • Hyaline cast
    • Fat globules
• Hypoalbuminemia
  • Lost in urine
  • Serum albumin reduces
• Edema
  • Loss of protein leads to reduced oncotic pressure 
• Hyperlipidemia
  • Loss of enzymes required for catabolism of lipids like lecithin, cholesterol, acyl transferase, lipoprotein lipase 
  • Increase in total cholesterol and LDL
  • When proteinuria is massive, triglycerides are increased along with VLDL
• Lipiduria 
• Acute kidney injury
  • Happens more in adults than in children 
  • ATN or patient having renal vein thrombosis 
  • In the case of persistent AKA, the reason is not minimal change disease
• Hyponatremia
  • Direct ion sensing electrodes are not seen
  • Pseudohyponatremia
    • Because of hyperlipidemia 
    • Dependent on serum osmolality to get to serum sodium 
  • Total calcium and vitamin D levels are low
    • Albumin is low 
    • Vit D binding globulin is low
    • Ionized calcium or vitamin D activity may be normal 

Complications Of Minimal Change Disease

• Infections
  • Low serum IgG
  • Urinary loss of properdin and factor B
    • This leads to infection with capsulated organisms like streptococcus pneumoniae
    • Immunization must be done in children with minimal change of disease
• Hypercoagulability
  • Loss of anticoagulant factors like protein C, S, and antithrombin 3
    • While there is an increased generation of coagulation factors 

Also Read: Valvular Heart disease: Types, Causes, Symptoms and Diagnosis

Indications for Renal Biopsy Of Minimal Change Disease

• Presence of
  • Atypical clinical features like persistent hypertension, AKI, and active sediments in urine.
  • A steroid-resistant nephrotic syndrome that is When there is no response to steroids, even for 4 weeks
  • Children > 12 yrs
    • It can be FSGS or minimal change disease
    • The treatment approach might change
    • <1 yr genetic cause of nephrotic syndrome 
  • Adults
    • It can be FSGS, minimal change disease, membranous nephropathy, C3 glomerulopathy, or amyloidosis. So, every adult requires a renal biopsy.

Natural History Of Minimal Change Disease

Treatment Of Minimal Change Disease

• Within a week, 95% of children become dry, their edema resolves, and proteinuria stops.
• Frequent relapses can be frequent relapse or steroid-dependent
  • Therapy varies in this. So it is important to mug up the definition 
• Cyclophosphamide shows more response in frequently relapsing nephrotic syndrome than in steroid-dependent nephrotic syndrome 
• Rituximab, or MMF are experimental therapy
  • Still, research is going on
• CNI must be continued for 1-2 years
• Cyclophosphamide is given only if the child has remission with steroids
  • Otherwise, there is a high chance of bladder toxicity 
• If there is a full-blown relapse, give steroids 
• Genetic etiology mostly can be FSGS
  • This leads to no response 
• Steroid-resistant nephrotic syndrome, CNI, is 1st line 
• Steroid-dependent nephrotic syndrome, again CNI
• In frequently relapsing nephrotic syndrome, cyclophosphamide is given.
• Symptomatic therapy like ACE inhibitors and ARBs are given to reduce proteinuria.

Hope you found this blog helpful for your NEET SS Nephrology Preparation. For more informative and interesting posts like these, keep reading PrepLadder’s blogs.