CHRONIC KIDNEY DISEASE AFTER LUNG TRANSPLANTATION

            In general, the majority of lung transplant recipients have normal kidney function at the time of transplantation.  In fact, chronic kidney disease is an important relative contraindication to transplantation at most centers.  A significant proportion of patients develop kidney disease after transplantation, and this complicates the medical management and can have a negative impact on outcome and quality of life.  Obviously, starting out with abnormal kidney function only increases the risk and severity of kidney disease after transplantation. 

            According to the International Society for Heart and Lung Transplantation (ISHLT) Registry, 25% of lung recipients have abnormal kidney function within one year of transplantation.  The majority of patients have mild or moderate kidney disease and manifest no symptoms or clinical signs.  However, approximately 10-15% have more advanced kidney disease that manifests with fluid retention and high blood pressure, and a small minority of patients requires dialysis.  Over time, kidney disease worsens and a greater proportion of lung recipients are affected.  In fact, almost 40% of lung recipients have chronic kidney disease within 5 years of transplantation, and 3% require dialysis. 

            The primary reason for kidney disease after solid organ transplantation is that calcineurin inhibitors such as cyclosporine and tacrolimus are toxic to the kidneys.  Yet, these drugs are indispensable for the majority of lung transplant recipients.  Calcineurin inhibitors cause kidney toxicity by constricting blood vessels and reducing blood flow to the kidney.  Initially, the toxicity is reversible but over time, the injury becomes progressive and irreversible.  Other medical co-morbidities including diabetes and high blood pressure can exacerbate the injurious effects of calcineurin inhibitors on the kidney.  Indeed, 85% of lung recipients have high blood pressure and 37% have diabetes within 5 years of transplantation.  For those afflicted with high blood pressure or diabetes, intensive treatment is important to reduce the adverse consequences of these diseases, and this is crucial for patients with kidney disease.

            Otherwise, the general approach to the management of calcineurin inhibitor induced kidney disease is to target lower blood levels of cyclosporine or tacrolimus.  In the early stages, this approach can ameliorate the kidney injury and although it may carry a higher risk of graft rejection, this strategy has not been associated with worse graft function or survival.  Another more aggressive approach is the withdrawal of calcineurin inhibitors.  An alternative agent is sirolimus, which has a significantly lower risk of kidney toxicity when used without a concomitant calcineurin inhibitor.  While experience with calcineurin inhibitor-free immunosuppression after lung transplantation is limited, some patients have been managed successfully with a combination of sirolimus, mycophenolate mofetil, and prednisone.  Nonetheless, this combination is probably not effective at preventing rejection for all patients, and an individualized approach balancing the risk of rejection and kidney failure is necessary. 

            Kidney disease can be clinically silent yet progressive for years.  In fact, symptoms are typically absent in early and even moderate stages.  Furthermore, lab results can sometimes underestimate the severity of kidney dysfunction; the serum creatinine is routinely measured with standard blood tests, but it can be an insensitive marker of kidney disease especially in older patients and those who are small statured.  As kidney function progressively worsens, patients typically develop edema, fluid overload, and more severe high blood pressure.  These complications are usually manageable with diuretics and anti-hypertensives, but these interventions cannot reverse the kidney damage.  Ultimately, kidney failure develops in some patients, and this manifests with nausea, anorexia, weight loss, and fluid overload. 

            Patients who develop frank kidney failure can be managed with two forms of dialysis.  Hemodialysis is usually performed three days a week in an outpatient dialysis center.  Each session lasts about three hours but is sometimes difficult to tolerate and many patients describe the treatments as "draining."  Alternatively, patients can be managed with home peritoneal dialysis with several treatments a day or an extended nightly treatment.  Kidney transplantation is the ultimate treatment for kidney failure, and the outcomes are generally very good.  However, the waiting time for kidney transplantation from a deceased donor can be several years long.  The alternative is transplantation from a living donor, usually a spouse or another relative.  Obviously, pursuing transplantation from a relative is a difficult individual and family decision but it reduces the waiting time significantly.  Less than 1% of lung recipients have a kidney transplant within 5 years of the lung transplant, but the outcome of the kidney transplant is usually very good.  Unfortunately, other lung transplant related complications are unavoidable and ultimately impact the long-term survival.