The dynamics of serum free light chain immunoglobulins after kidney transplantation

Patients developing end stage renal disease (ESRD) are characterized by an accumulation of metabolic waste products in the blood. The majority of these waste products are efficiently removed during dialysis. However, kappa and lambda serum free light chain immunoglobulins (sFLC Igs) that are overproduced (10 to 40%) by all human plasma cells remain in the blood circulation of dialysing patients. Normally, these sFLC Igs are internalized in the proximal tubules of the kidneys by low-affinity, high capacity receptors that provoke sFLC Ig proteolysis and therefore reflect kidney function. Notably, oversaturation of this process by elevated sFLC Ig levels leads to cast formation in the distal tubule that induces further kidney damage in patients with ESRD. For these reasons we investigated the dynamics of kappa and lambda sFLC Igs in the blood of patients receiving kidney transplantation and whether sFLC Ig levels reflect kidney function.We show that the serum levels of kappa and lambda FLC Igs are elevated in all tested patients awaiting kidney transplantation as compared to healthy controls, indicating that dialysis and the alternative sFLC Ig removal mechanism of the liver fail to maintain normal sFLC Ig levels. This elevation was irrespective of immunization status of the patient. Upon kidney transplantation we observe a rapid decrease of sFLC Ig levels in 23 out of 25 patients with immediate graft function and we show intermediate decrease of sFLC Ig levels in 15 out of 23 patientswith delayed graft function. In general we observe faster normalization of kidney function in patients receiving an organ of living donors as compared to postmortem donors. In the latter group the heartbeating organs show faster sFLC Ig normalization as compared to non-heartbeating donors, which also reflects kidney function. Taken together our data illustrate that kappa and lambda sFLC Ig levels reflect kidney function in immunized and non-immunized patients after kidney transplantation. At present we are investigating whether sFLC Igs are a more sensitive biomarker for rejection or delayed kidney function.