• Cmv infection refers to cytomegalovirus which is a subtype of human herpes virus type V 

• It is one of the most common infectious agent which affect the human body after 1month or 100 days of  the post transplantation of kidneys 

• The source of infection or entry can be through various ways which may be surgical related,Donor derived, environmental related, Reactivation of already existing virus 

• First route is through blood and secondly from any other body fluids such as saliva,genital secretions,urine or donor Transplanted organs   

• The factors that influences the CMV infection depends upon the serostatus of both the receiver or donor

• Cytomegalovirus can be primary (active)or secondary (latent)

• In Primary CMV infection the virus directly invades the epithelial cells and tends to multiply . The most  common sites to invade are oral mucosa, gastrointestinal or urinary mucosa 

• After successful invasion the virus breakdown the cytoskeleton which maintains the cell structure in shape 

• In 25-30% patients primary infection incidence is more severe compared to secondary infection

• Where as in secondary CMV infection the virus remains dormant for several months to years which infects monocytes in the blood and sets up in latent infection 

• Thus results in enlarged cells with typical owl’s eye appearance .This happens at a microscopic level

• They look for an opportunity to reactivate at times when immune system weakens and cause disease 

• Can be symptomatic or asymptomatic

• If symptomatic then it is associated with the following signs & symptoms

• Prolonged Fever
• weakness
• Nausea ,Vomitings 
• Diarrhea 
• Cough,shortness of breath
• Abdominal Pain 
• Difficulty in swallowing,pain
• Jaundice
• Blurring of vision or total blindness (sometimes)
• Scotoma(partial vision loss)
• Hepatitis /colitis 
• Leukopenia 
• Allograft injury 
• Rise in susceptibility in infections /opportunistic infections
• Increased risk episodes of acute rejection 
• Survival of graft is diminished
• Altered mental status
• Seizures

    Asymptomatic  in case of latent infection

DIAGNOSIS 

• Detecting the virus by Polymerase chain reaction which is an serological test with less diagnostic value 

The results are sensitive and more specific 

• Blood Tests is done to detect the virus antibodies,low count of WBC ‘s  ,enlarged cells with intranuclear inclusion bodies (monocytes) 
• Positive Blood/Urine /sputum cultures  in presence of virus 
• Immunological assays  shows CMV specific antibodies in blood 

If CMV IgM is increased then it is an acute infection 

If CMV IgG is increased then it is an secondary or latent  infection 

• Biopsy of the donor organ 

  TREATMENT 

There is no permanent cure for the CMV virus after the transplantation the only choice left is to prevent beforehand to stop further spread of the infection 

The therapy comprises  of 3 steps 

1. Prophylactic
2. Pre-emptive 
3. Therapeutic 

prophylactic treatment is advised to prevent the disease from occurring in the near future.These drugs are advised to patients who are at greater risk of viral replication 

It is usually done at the period of 3–6 months after transplantation 

Antiviral drugs are prescribed 

1.Ganciclovir 

2.Valganciclovir-900 mg for 3 – 9 months

 Restricted use in case of GFR <10  

3.Acyclovir-200mg 

4.Valacyclovir

5.CMV IVIG (intravenous immunoglobulin)

6.Foscarnet (resistant conditions)

The protocol followed is 

• If Donor + / Recipient – (50-75%)  then 9months prophylactic therapy with VGCV(Valganciclovir)
• Donor + / Recipient + (25-40%)then 3months therapy with VGCV
• Donor – /Recipient + then 3months therapy with VGCV
• Donor – / Recipient – (<5%)  then 3months therapy with Acyclovir for Herpes simplex and after that 6weeks after treatment of rejection

Pre-emptive treatment

The preemptive value of virus replication determines the initiation of the treatment 

It only provides the prevention from the asymptomatic CMV leading to further  Spread of infection

Therapeutic therapy includes 

• Ganciclovir -intravenous 5 mg/kg for 2-4 weeks followed by oral 1gm ×3
• Valganciclovir -900 mg for 21 days if PCR negative twice 1week apart 
• Consolidate the therapy with VGCV 900mg for 3 months 
• IVIG in cases of severe or relapsing disease 
• Stop metabolite 

BKV INFECTIONS IN POST KIDNEY TRANSPLANT 

•  BK virus is another most common virus that affects individuals post transplantation
• Also called as polyomavirus commonly present in childhood which remains latent in renal epithelium or in lymphoid cells 
• The Mode of spread is more or less  similar to that of the CMV through body secretions ,urine or sometimes mother to child 
• It is highly prevalent virus usually transmitted by an infected kidney from a seropositive donor 
• Not forget to mention there is higher risk of developing Nephropathy associated with BKV in seronegative recipient
• In almost 40-50%of cases the virus attacks within 3 months after transplantation
• Usually asymptomatic and causes no harm but when the body has weak immunity or under immunosuppression this virus finds an opportunity to cause the damage resulting in symptoms  
• During first year out of 25-30%patients present with viruria shows viremia in 12% out of which only 1-10% suffer BKV associated Nephropathy
• And hence the symptoms develops slowly with rise in level of serum creatinine indicates the presence of viral nephropathy   
• The most common symptoms are 

•  Fever ,weakness
• Muscle pain
• Seizures
• Blurred vision
• Discolored urine(red / brown)
• Pain /difficulty during urination
• Need to urinate more times  than usual 
• Cough,cold 
• Trouble during breathing 

What are the determinants of risk?

Patient related 

• The older age group
• Male
• immunocompromised diseases such as HIV / Diabetes etc

serostatus before the transplant (negative)

• The person who undergone transplantation 
• Any surgical procedures 

Organ related 

• Degree of mismatching of HLA
• Any prior rejections 
• Renal injury
• Latent infection load 

Viral related

• Genotype of virus 
• Viral fitness 
• Non Coding control region rearrangement / NCCR rearrangement

Histologically they grouped in to 3 stages 

 Stage A- with not much significant changes evident

Stage B -with significant inflammatory cells and inflammation to tubules

Stage C – with more than 50% of fibrosis and atrophy is seen 

CLINICAL MANIFESTATIONS 

Progressive decrease in kidney function

• Nephropathy
• Ureteral stenosis 
• Hemorrhagic cystitis 
• Malignancy 
• Obstructive Uropathy 
• Interstitial nephritis 

SCREENING TESTS 

• Presence of infected epithelial cells in urine is evident known as decoy cells 

                 Only indicative of high level of viruria

                 Poor sensitivity for PVAN

                 No prognostic value of progression to viremia 

• Viruria in BK urine PCR 
• Viremia in BK plasma PCR
• Blood & urine  tests to evaluate viral load ,  pus cells in urine & microscopic hematuria 
• Biopsy is done to confirm the Presence  

Viruria takes a few weeks to make evidence of viremia which in duration of 1-2 weeks turns into BKV associated nephropathy and then the end stage .

TREATMENT 

There is a only a better prognosis option left with the pre-emptive therapy by discontinuation of Immunosuppressive drugs shows 95 % of  viral clearance .So the first line therapy is  

1.Reduction of immunosuppressants 

• Cut MMF(mycophenolate) /MPA to Half or hold 
• Target FK (Tacrolimus)through goal (~4)
• Prednisone EOD or 2.5mg Q.D
• Switching FK to CSA ( till reaching the goal of 50-100)

2.Intravenous immunoglobulin 

• 0.5g/kg _ 4 doses EOD
•  avoid when DSA is checked 2_3 weeks priorly

4.Cidofovir 

• Intravesical -5mg/kg or Intravenous -<1mg/kg ,Four injections twice with once per 2 weeks

• Switch  MMF/MPA to leflunomide -40-60mg/d

• Ciprofloxacin

5.Ureteral stenosis – placing balloon or stent to reduce obstruction 

6.Hemorrhagic cystitis in bone marrow- hydration ,by evacuation of clot 

7.If presence of underlying conditions like HIV then lamivudine ,zidovudine is prescribed 

CONCLUSION

• Regular screening test and monitoring is required in case of progressive decrease in kidney function to manifest the infection associated dysfunction
• Post-treatment prophylactic therapies should be strictly followed to prevent further spread of infections