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Understanding Kidney Transplantation

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Understanding Kidney Failure

Kidneys are your body’s filters. They purify blood several times a day, maintain your body’s fluid and electrolyte balance and produce urine.

So when the kidneys fail to function, your body starts getting poisoned. Each of your kidneys comprises a million microscopic filtering units called nephron. The most dangerous fact about kidney or renal failure is that one might not know about it till 90% of the function is lost.

The symptoms of kidney or renal damage include symptoms like swollen ankles, vomiting, weakness, poor sleep, and shortness of breath. If not addressed medically, the kidneys will eventually become dysfunctional – a condition that’s life threatening.

What causes kidney failure?

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Chronic kidney disease (CKD) occurs when your kidneys have been malfunctioning for more than 3 months. It’s an irreparable, life threatening condition and there might be no visible symptoms at all.

Diabetes (types 1 and 2), high blood pressure, immune system diseases such as Lupus and chronic viral illnesses like AIDS, Hepatitis B and Hepatitis C can also cause kidney failure.

The other reasons for kidney failure include:

Multiple episodes of urinary tract infection

Post-strep infection

Polycystic kidney disease

Inherited kidney diseases

Congenital or birth defects - In many cases, the defect is rectified while the baby is still in mother’s womb; whereas those with major complications can only be managed at a later stage.

Drugs and toxins, including long-term use medications like NSAIDs (Non Steroidal Anti Inflammatory Drugs

Long-term exposure to certain chemicals

What is Kidney Transplant?

Kidney transplant is the process of replacing the diseased kidney with a healthy, donated kidney. It is recommended only if the kidneys are so damaged that they cannot be managed medically (Chronic Kidney Disease or End Stage Renal Disease).

In some cases, transplant might not be a practical solution if the patient has an active infection or another life-threatening disease such as cancer, severe heart or lung diseases.

Fortunately, according to worldwide figures, the success rate of kidney transplant is above 95%. This not only comes as a reassurance for those opting for transplant, but also reaffirms the fact that kidney transplant is indeed an effective mode of treatment.

What are the types of kidney transplant?

There are two types of kidney transplants: Live donor Transplant and Cadaver Transplant

When a person is transplanted with a kidney from a live donor, it is called Live Donor Transplant. The donor could be anyone - a family member, friend, colleague or even a random person who is generous enough to gift life by donating one of his/ her kidney.

Usually, the success rates of kidney transplants in which the donor and recipient belong to one family (parent/ sibling) are higher. This is because of high donor-recipient compatibility, which means the chances of rejection are very low. A live donor makes things easy as the waiting period is lesser and the patient gets well faster.

Cadaver transplant is when the kidney is got from a donor who is certified brain-dead. He or she would have would have signed up for donation before death. The kidney is surgically removed after obtaining consent from the deceased’s family and transplanted in the recipient.

ABO Incompatible Kidney Transplantation

ABO blood group matching between the kidney donor and the recipient was considered to be absolutely essential for a successful outcome of a kidney transplantation. A donor with blood group O was considered as a universal donor and AB group considered a universal recipient. A recipient with blood group A could receive a kidney from a donor with blood groups, either A or O ; likewise , a recipient with blood group B could receive a kidney with blood group B or O. Thus, ABO incompatibilty had long been considered a contraindication to kidney transplantation. This lead to a situation wherein many relatives who were willing to donate a kidney to their near ones were not accepted as kidney donors. This perception remained till the first reports of successful ABO incompatible transplantations were published from Belgium in 1982. Such transplants are now being done in Japan, US and Europe.

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Blood Group Antigens & Antibodies

ABO antigen system is composed of oligosacharide expressed on erythrocytes(Red blood cells). These antigens are also expressed in endothelial cells, glomeruli and tubules. Antibodies to A and B antigens are formed during early infancy. These antibodies are predominantly of IgM class; but can also be of IgG and IgA class, especially in blood group O individuals.

The immune system forms these antibodies against whichever ABO blood group antigens are not expressed on the individual’s RBCs. Thus, group A individual has anti B antibodies and vice versa; both anti A and anti B antibodies are found in individuals with blood group O; people with AB group do not have any antibodies. Successful ABO incompatible kidney transplantation requires removal of these antibodies against the donor blood group antigen; this process is called desensitization.

Desensitization for ABO incompatible Transplant

Recipients are subjected to desensitization procedures prior to transplant to lower anti A / anti B antibody levels to acceptable limits.

These strategies include

  • Removal of antibodies using Plasmapheresis or immunoadsorption
  • Reducing further production of AB antibodies using Rituximab
  • Immunomodulation using intravenous immunoglobulin (IV Ig)

Desensitization protocols do vary a bit across various transplant centres; almost all the centres use a combination of above methods to achieve target anti A / anti B levels. Acceptable antibody levels prior to transplantation vary from 1:8 to 1:16

Maintenance immunosupression in these patients consists of the triple drug regimen that include Tacrolimus, Mycophenolate mofetil and Prednisolone.

Patient & graft outcome

In the past, patient and graft survival following ABO incompatible transplantation was reduced by high rates of sepsis related mortality and antibody mediated rejections. Recent data reveal excellent patient and graft survival in these patients; the results comparable to ABO compatible transplant are achieved in some centres ; current data shows 5 year survival rates of more than 90%. Initial studies reported are incidence of antibody mediated rejections to be 20-30%. However with Rituximab based regimens, the rejections have reduced significantly, to as low as 5%.

Compared with ABO compatible transplantation, these recipients are at a higher risk of infections including pneumonia, urinary infections and wound infections. These patients are also at higher risk of viral infections caused by cytomegalovirus, B.K virus. Higher rates of perioperative bleeding is seen in ABO incompatible transplant recipients, likely due to depletion of clotting factors by plasmapheresis. This can be avoided by carefully correcting coagulopathy prior to transplant by fresh frozen plasma infusion. A higher rate of lymphoceles has been reported, the reasons for which are currently unclear. Significantly, despite more intensive immunosupression, there has been no difference in risk of malignancies compared to ABO compatible transplant recipients.

ABO incompatible transplantation has come a long way since its early days. The patient and graft survival are now comparable to ABO compatible transplantation. These encouraging results would help several patients who lack a blood group compatible donor to realise their dream of a successful kidney transplantation. The Renal transplant Unit at Aster Medcity, Kochi does ABO incompatible transplants with excellent results.

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Pediatric Renal Transplantation

A second lease of life for children with End Stage Renal Disease

Kidney transplantation is considered the treatment of choice for end stage renal disease (ESRD) in children, as it provides a much better quality of life, productivity, growth and longer patient survival than what can be achieved with any modality of dialysis. Graft survival has improved significantly in recent years, mainly due to improved immunosuppressive strategies.

Chronic Kidney Disease (CKD) in children

There are distinct geographic differences in the reported causes of CKD in children ; this is due to environmental, racial, genetic, and cultural (consanguinity) differences. A substantial proportion of children who develop CKD early in life have congenital anomalies of the kidney and urinary tract - obstructive uropathy , aplasia, hypoplasia, or dysplasia of kidneys . Although the best treatment modality for ESRD in children is renal transplantation, lack of high quality health care resources and expertise in many countries limits the widespread use of renal transplantation in young children.

Although the number of children with ESRD in need for renal transplantation is small compared with adults, the problem associated with renal transplant in children are numerous and varied. Children and adolescents with ESRD would be able to achieve normal growth, normal cognitive and psychological development following successful kidney transplantation..

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Preemptive Transplantation

Preemptive transplantation (PET), which denotes transplantation prior to the initiation of dialysis, has recently been growing in popularity, as it is postulated that transplanting children before they develop symptoms of severe uremia avoids many of the associated long -term complications of ESRD and dialysis. Avoiding dialysis and all its hazards is one of the most important advantages of PET. Dialysis is regarded by most children and parents, as an inconvenient experience requiring frequent hospital visits for hemodialysis and frequent dialysate exchanges for peritoneal dialysis. Therefore, PET provides a better option for the prevention of short stature with all its co-morbidity and psychosocial implications. As most of the effects on cognitive development are related to uremia, it is postulated that PET will have further favorable effect over transplantation after a period of dialysis. Moreover, PET is also more cost effective. Therefore, decreasing the period on dialysis or even avoiding dialysis altogether whenever appropriate, has a significant effect on the cost of care in children with ESRD.

Types of Kidney Transplantation in Children

  • Deceased donor transplantation – The child can get a kidney from a healthy person who has suffered a brain death. To obtain a deceased donor kidney, the child must be registered with the Kerala Network for Organ Sharing (KNOS) and be on the waiting list.
  • Living donor renal transplantation - A healthy relative can donate one of his/her kidneys to the child. Donors for children are often their parents, siblings, or grandparents. Parents of a child with kidney disease are usually the best donors, because they often have the same blood group and are a good tissue match with the recipient.

Immunosuppression

Steroid free regimens may be tried in children to avoid steroid related adverse effects, especially related to growth and mineral metabolism. The other drugs used are similar to adult transplantation, namely Tacrolimus and Mycophenolate Mofetil.

Renal Allograft Survival

Renal allograft survival in children has improved substantially over the last two decades, with several large registry studies from abroad reporting graft survival approaching 80% at three years and 75% at five years. Renal allograft survival in infants is now similar to that in older children, and short term deceased donor allograft survival in children now approaches that of living donation.

Conclusion

Transplantation is currently the best option for children with ESRD. Surgery and modern immunosuppression have demonstrated excellent results, provided the children are managed in a center with experience in the management of all aspects of pediatric renal transplantation.

The Kidney transplant Unit at Aster Medcity has successfully done 30 paediatric transplantations . This includes very small children (aged 2 years and weighing around 10 kilograms) and children with complex urinary tract anomalies. Robot assisted kidney transplants in children are done at our institution with outstanding results. The graft survival in children after kidney transplantation at our centre has been 98% at the end of three years. This has been possible because of the surgical expertise at our centre, experienced Anaesthesiology and Nephrology teams at Aster Medcity ,which has an excellent infrastructure for health care.

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Robot Assisted Kidney Transplantation

Nephrologist’s Perspective :

Minimally invasive surgeries are gaining popularity all over the world. Laparoscopic surgery is being practiced in various surgical specialties. Robotic surgery is the new kid on the block and has several advantages over laparoscopic surgery, especially in certain surgical procedures including kidney transplantation.

The first documented use of a robot-assisted surgical procedure was in 1985 when the PUMA 560 robotic surgical arm was used in a delicate neurosurgical biopsy. In 1988, the same PUMA system was used to perform a transurethral resection. In 2000, the da Vinci Surgery System (Figure 1a), became the first robotic surgery system approved by the FDA for general laparoscopic surgery. Its three-dimensional magnification screen allows the surgeon to view the operative area with the clarity and high resolution. The one- centimeter diameter miniaturized operating arms and wrist like features of the operating arms precisely replicate the skilled movements of the surgeon at the controls, improving accuracy in small operating spaces. The da Vinci robotic surgical system has the advantages of three-dimensional vision, control of the camera by surgeon, articulated wristed instruments with seven degree of movements; these features make suturing more perfect and it tracks surgeon's movements. This eliminates human tremor which is essential for performing a good vascular anastomosis. Robotic procedures are rapidly becoming the new standard of care with rapid advancements in technology.

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Robot assisted kidney transplantation (RAKT)

Traditionally, kidney transplantation is carried out through an incision in the lower abdomen; this requires a long incision (often above 15cm), especially in obese patients and children. Larger wounds are associated with more wound related morbidity (more pain, longer convalescence period and postoperative recovery, and poor cosmesis). Open kidney transplantation through a small incision was tried but had significant challenges especially for vascular anastomosis; hence it is not widely practiced.

The first RAKT was performed in France in 2002 but till 2009, it didn’t gain much attention. Initial experience about RAKT in 28 cases was published from Chicago, which showed promising results especially in obese patients. RAKT is a transperitoneal procedure compared to open kidney transplant (OKT) which is performed extraperitoneally. The drawbacks of transperitoneal approach include potential for bowel injury, undetected postoperative bleeding and urine leak. The graft was placed partially intraperitoneal and it would pose a challenge if a graft kidney biopsy has to be done in the post transplant period. Another complication was torsion of kidney at the time of final placement. Retroperitoneal approach in placing the graft was tried but had technical challenges. Maintaining intraoperative cooling was another challenge which was maintained by using ice slush; however it resulted in systemic hypothermia as the peritoneal cavity was exposed to ice slush. Tremendous technical advancements has been made in the last decade in the field of RAKT and the transplant surgeon in our centre Dr Kishore (Figure 1b) has contributed a lot. Our surgeon published an experience of total extra peritonealisation of the graft in 34 cases which would negate the above mentioned complications. The salient feature of our technique is fashioning of the peritoneal flap in such a manner by which the kidney is totally placed in the extra peritoneal space. This offers distinct advantages over existing techniques. In the intraoperative period, the reflected portion of the bladder and the adjoining peritoneum act as a barrier to the kidney covered in ice slush from having direct contact to underlying sigmoid colon. This allows free placement of ice slush over the kidney without concern of hypothermic damage to colon. This technique would mimic that of open transplantation and post transplant kidney biopsy is easy. A total extraperitoneal RAKT without creating a pneumoperitoneum should be the ultimate goal but is challenging with current robotic instruments and would be a reality in future.

Advantages of RAKT are less blood loss, less pain, shorter hospital stay, speedy recovery, less postoperative complications, lower incidence of wound related complications and better cosmesis (Figure 2) when compared to OKT.

Disadvantage are higher cost when compared to open surgery and the availability of expertise.



Figure 1: a) Da Vinci surgical robot with robotic arms, b) Dr. Kishore, our robotic surgeon, at the console of the Da Vinco robot

The diuresis following robotic transplantation is not different from open transplantation. Overall graft outcomes at one month and three months are not different in various studies, including our centre; rejections episodes were not different between the two techniques. Though it was initially considered in obese individuals due to discrete advantages, it is now being considered in all individuals including children with good results. Aster Medcity, Kochi has successfully done 234 kidney transplants so far. Kidney graft survival in our centre is 99%. at one year and 98% at 5 years.

Not many centres in the world are practicing RAKT. In India it is gaining more popularity and momentum. A couple of centres in North India has done the highest number of cases. In South India, Aster Medcity, Kochi was the first centre to start robotic kidney transplantation and has done maximum number of cases. So far 113 RAKT surgeries have been done at our institution with excellent results; this includes both children and adults. Our transplant unit is able to perform RAKT in children with complex congenital anomalies of urinary tract. This minimally invasive surgery would be the standard of care in future.



Figure 2: Comparison of scar in open surgery (red arrow) and robotic surgery (blue arrow)

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What are the pre-transplant formalities?

You will have to go through a series of investigations before the surgery to ensure that the donor kidney matches your tissue and blood type. You will also be screened for other health problems including heart or lung diseases.

After these tests, you will be enlisted on the transplant list and also on the organ sharing network list. As soon as a matching recipient is available, we will let you know; and if all factors are favourable, our entire team will work as one to ensure you undergo the surgery without any issues.

What are the possible post-transplant risks?

The post-surgical risks, like every other transplant surgery, include rejection, infection, bleeding or reaction to anaesthesia.

Rejection happens when the body fails to recognise the new kidney and fights to destroy it. During the first few weeks or months post-surgery, your body may try to reject your new kidney. This is called acute rejection and occurs in 25 - 55% of the recipients. You’ll be given immuno-suppressants to counter this problem. Remember, it is mandatory to continue these medicines for the rest of your life.

There is also a chance of chronic rejection - a gradual, progressive loss of kidney function that may occur over many years. Unfortunately, there’s no known treatment for chronic rejection and the patient may have depend on dialysis again or opt for another transplant.

Aster Centre of Excellence in Multi-Organ Transplant has a very strong infection control system that’s managed by a highly-trained team of infectious diseases & infection control Physicians. Besides, we also have advanced technology like the HEPA Filter that purifies air to 0.3 microns, creating a safe and sterile environment for the patient.

What will it be like after the surgery?

You’ll be under continuous medical observation for 7 to 10 days post surgery, so that we can check whether your new kidney is functioning properly. At times, the new kidney might take some time to start functioning and produce urine. You might have to undergo dialysis till then and also take medications like diuretics to help the kidney expel excess water and salt from your body.

Our nurses and rehabilitation experts will take good care of you and guide you through your recovery.

We have state-of-the-art hemodialysis and peritoneal dialysis facility, complete with a water treatment plant to ensure high-quality dialysis for patients.

Follow-up

It is very important to visit your consulting doctor regularly and undergo all prescribed follow-ups and test to make sure that your new kidney is functioning well. Remember, a transplant surgery is a second chance at life and you need to be responsible for your own well-being.

Centre of Excellence in Nephrology & Urology

Nephrology Unit

The unit provides all subspecialty services that available at present globally. There is no service related to Nephrology for which a patient has to be sent elsewhere for treatment.

The niche areas are :

  • General Nephrology : Patients of all ages (Children and adults) with all types of kidney diseases can be offered treatment.
  • Hemodialysis unit:

Patients of all ages (children & adults) are provided dialytic treatment.

Awarded the certificate for the Best Dialysis service provider (National award for Excellence in Healthcare) in the country two times.

The unit, which functions round the clock (24 X 7) , has completed 69,000 treatment sessions of hemodialysis so far.

Incidence of Catheter related blood stream infection (CRBSI) due to haemodialysis catheters is one of the least in the country and is on par with international standards.

This unit has a very low incidence of hypotension, much lower than international standards

All forms of hemodialysis, including hemodiafitration are available

Different forms of Continuous renal replacement therapy available

Membrane Plasmapheresis for various types of Neurological diseases, hepatic failure, autoimmune and renal diseases is being done

Extracorporeal therapies, for children and adults with liver diseases, Neurological diseases,Cardiac failure and postcardiac surgery & liver surgery patients.

Extracorporeal support for patients with sepsis and critically ill patients in ICUs.

  1. Peritoneal dialysis unit : All forms of acute and chronic peritoneal dialysis

Training of patient and relatives on home PD

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Automated peritoneal dialysis

  1. Kidney transplant unit
  2. Completed 240 kidney transplants so far.
  3. Paediatric kidney transplantation - Leading Paediatric kidney transplant centre in South India
  4. Robot assisted kidney transplantation - Maximum number of Robotic renal transplants in South India (completed 110 cases) and we are fourth in the world in terms of numbers.
  5. Robot assisted kidney transplantation in children
  6. ABO incompatible kidney transplantation
  7. Kidney transplantation in children with complex urinary tract anomalies
  8. Able to perform kidney transplants in very small children- First ever live related donor combined (simultaneous) liver and kidney transplantation in the youngest child (one year and 7 months old, weighing just 7 kilograms) has completed 3 years following the transplant surgery and is doing well.
  9. Excellent kidney transplant outcomes: Graft survival and patient survival following renal transplant is on par with the international standards at one year and five year post transplant - Graft survival at one year is 98.6 %, at five years it is 95 % - these figures are better than some of the best transplant centres across the globe.

Surgical complications associated with kidney transplant surgery in our centre is almost nil.

Time to discharge following kidney transplantation surgery is only 5 to 6 days in our unit.

  1. Kidney transplantation for the senior citizens (above 60 years of age)
  2. Transplantation using kidney donors with multiple vessels
  3. Simultaneous multiorgan transplantations.
  4. Tailoring of immunosuppression based on time bound protocol based graft biopsies.

E. Interventional Nephrology :

1. Vascular access salvage procedures for arteriovenous fistula malfunction

2. Real time ultrasound guided kidney biopsies for diagnosis of kidney diseases

F. Publications & Academic achievements

  1. 12 Publications from Department of Nephrology in National and international journals. ; 4 articles accepted for publication (awaiting publication)
  2. Chapters by Dr.V.N.Unni in 3 books
  3. One CMT student under the Educational supervisorship of Dr.Unni completed the three parts of MRCP and qualified for MRCP degree by the Royal College, UK
  4. Faculty and trainees from Nephrology presented papers at the World Congress of Nephrology, Annual conference of Indian Society of Nephrology, Indian Society of transplantation as well as Kerala societies. Awards were won for papers at different levels.
  5. Dr.Unni has been an examiner for the PACES examination of the Royal College, UK for the last four years.
  6. The dept. is accredited by the National Board of Examinations for DNB in Nephrology & Urology.

Personal achievements

  1. Dr.V.N.Unni, lead senior consultant , was awarded Fellowship of American Society of Nephrology
  2. Dr.V.N.Unni has completed over 1100 Renal transplantations in his career so far
  3. Dr.Vinod Kumar was awarded the MRCP, Certificate Course in Nephrology and FASN

G. Research projects

  1. Two Research projects (one National & one International) being conducted by department of Nephrology.
  2. Thesis research work being done by six DNB trainees

H. Multidisciplinary service: Ability to provide multidisciplinary care to patients with complex multisystem disease states.

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Doctors

Dr. V. Narayanan Unni

Senior Consultant
Nephro Narayananunni

Dr. Suresh G Nair

Senior Consultant
Anaesthesia Sureshnair

Dr. Vinod Kumar K

Consultant
Nephro Vinodkumar

Dr. Sangeeth P.S

Consultant
Anaesthesia Sangeeth

Dr. Kishore T.A

Consultant
Nephro Kishore

Dr. Rajappan Pillai. P

Consultant
Child Rajappanpillai

Dr. Anup R Warrier

Consultant
Infectious Anupwarrier

Dr.Nanda D Kachare

Consultant
Laboratory Nanda

Dr. Bipi PK

Consultant
Nephro Bipi

Dr. Vishnu Raveendran

Consultant
Nephro Vishnuraveendran
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