Anti-phospholipase A2 receptor antibodies in recurrent membranous nephropathy.

About 70% of patients with primary membranous nephropathy (MN) have circulating anti-phospholipase A2 receptor (PLA2R) antibodies that correlate with disease activity, but their predictive value in post-transplant (Tx) recurrent MN is uncertain. We evaluated 26 patients, 18 with recurrent MN and 8 without recurrence, with serial post-Tx serum samples and renal biopsies to determine if patients with pre-Tx anti-PLA2R are at increased risk of recurrence as compared to seronegative patients and to determine if post-Tx changes in anti-PLA2R correspond to the clinical course. In the recurrent group, 10/17 patients had anti-PLA2R at the time of Tx versus 2/7 patients in the nonrecurrent group. The positive predictive value of pre-Tx anti-PLA2R for recurrence was 83%, while the negative predictive value was 42%. Persistence or reappearance of post-Tx anti-PLA2R was associated with increasing proteinuria and resistant disease in 6/18 cases; little or no proteinuria occurred in cases with pre-Tx anti-PLA2R and biopsy evidence of recurrence in which the antibodies resolved with standard immunosuppression. Some cases with positive pre-Tx anti-PLA2R were seronegative at the time of recurrence. In conclusion, patients with positive pre-Tx anti-PLA2R should be monitored closely for recurrent MN. Persistence or reappearance of antibody post-Tx may indicate a more resistant disease.

Very early recurrence of anti-Phospholipase A2 receptor-positive membranous nephropathy after transplantation.

Membranous nephropathy is a common cause of adult nephrotic syndrome, with recent evidence suggesting that 70% of idiopathic disease is associated with anti-Phospholipase A(2) receptor autoantibodies. We describe a 63-year-old man with membranous nephropathy who underwent a kidney transplant and developed recurrent membranous nephropathy with fine granular co-localization of Phospholipase A(2) receptor and IgG evident on transplant biopsy on day 6 and elevated circulating levels of serum anti-Phospholipase A(2) receptor autoantibody that declined over time in conjunction with improvement in the serum creatinine and urinary protein. This is a very early case of Phospholipase A(2) receptor-associated recurrent membranous nephropathy with circulating anti-Phospholipase A(2) receptor autoantibody, which supports the emerging evidence that idiopathic membranous nephropathy is an autoimmune disease.

Arginine uptake is attenuated through modulation of cationic amino-acid transporter-1, in uremic rats.

Endothelial cell dysfunction (ECD) is a common feature of chronic renal failure (CRF). Defective nitric oxide (NO) generation due to decreased endothelial NO synthase (eNOS) activity is a crucial parameter characterizing ECD. L-arginine is the sole precursor for NO biosynthesis. Among several transporters that mediate L-arginine uptake, cationic amino-acid transporter-1 (CAT-1) acts as the specific arginine transporter for eNOS. Our hypothesis implies that CAT-1 is a major determinant of eNOS activity in CRF. We studied glomerular and aortic arginine uptake, CAT-1, and CAT-2 messenger ribonucleic acid (mRNA) expression, and CAT-1 protein in: (a) rats 6 weeks following 5/6 nephrectomy (CRF), (b) sham-operated animals, and (c) rats with CRF treated orally with either atorvastatin or arginine in drinking water (modalities which have been shown to enhance eNOS activity and improve endothelial function). Both glomerular and aortic arginine transport were significantly decreased in CRF. Treatment with either arginine or atorvastatin abolished the decrease in arginine uptake in CRF rats. Using reverse transcriptase-polymerase chain reaction and Northern blotting, we found a significant increase in glomerular and aortic CAT-1 mRNA expression in CRF. Western blotting revealed that CAT-1 protein was decreased in CRF, but remained intact following arginine and atorvastatin administration. Renal and systemic arginine uptake is attenuated in CRF, through modulation of CAT-1 protein. These findings provide a possible novel mechanism to eNOS inactivation and endothelial dysfunction in uremia.