Abnormal kinetics of erythrocyte sodium lithium countertransport in renal transplant recipients.

Cardiovascular disease is now the most common cause of death in renal transplantation. Cyclosporine (CsA)-associated hypertension might be a major cause of cardiovascular risk factors. There is evidence suggesting that one mechanism of CsA toxicity might be mediated through alteration of membrane lipid peroxidation, which can activate cellular pathways. Erythrocyte sodium lithium countertransport (Na/Li CT) is a sensitive membrane protein that is abnormal in several hypertensive-related diseases. We have studied the kinetics of erythrocyte Na/Li CT in 38 renal transplant recipients. Group 1 (15 patients) received CsA, azathioprine, and prednisolone (C+A+P), Group 2 (15 patients) CsA and prednisolone (C+P), and Group 3 (8 patients) azathioprine and prednisolone (A+P). Compared with the normal subjects, the Michaelis constant for extracellular sodium (Km) of erythrocyte Na/Li CT was lower among the CsA-based regimen groups (C+A+P and C+P), but not the A+P group. The maximum velocity (Vmax)/Km ratio was also higher among the C+A+P and C+P groups than the A+P group. These abnormalities of Na/Li CT kinetics might be due to abnormalities of cell membrane functions, caused by immunosuppressive drugs, particularly CsA. Further studies involving the effect of CsA on the physiological function of membrane thiol proteins are required.

Erythrocyte sodium lithium countertransport in renal transplant recipients with mycophenolate mofetil and low-dose cyclosporine.

Hypertension, a common complication after renal transplantation, has many potential etiologies. Erythrocyte sodium lithium countertransport (Na/LiCT) is a sensitive membrane protein that has been observed to be abnormal in several hypertension-related diseases. We have shown that the kinetics of Na/LiCT were abnormal in renal transplant recipients treated with usual dose of cyclosporine (CsA). We postulated that CsA might be a cause of post-renal transplantation hypertension. There is evidence showing that the severity of CsA nephrotoxicity is dependent on the dose. Mycophenolate mofetil (MMF) may allow CsA dose reduction without increasing the risk of rejection. We studied the impact of CsA dose reduction in association with MMF on the kinetics of erythrocyte Na/LiCT in renal transplants. In 15 renal allograft recipients, 2 g/d MMF were introduced and the CsA dose reduced to reach whole-blood levels between 70 and 100 ng/mL within 1 month. CsA doses and levels, renal function parameters, blood pressure, and the kinetics of Na/LiCT were evaluated before and 6 months after CsA dose reduction. Overall, renal transplant recipients with usual doses of CsA showed a lower Km with a higher Vmax/Km ratio for erythrocyte Na/LiCT than normal controls (Km, 40 +/- 4 vs 74 +/- 11; P <.05; Vmax/Km, 10.2 +/- 1.7 vs 6.1 +/- 0.9; P <.05). After 6 months of CsA dose reduction, the Km and Vmax/Km of Na/LiCT were similar to those of normal controls (Km, 66 +/- 8 vs 74 +/- 11; P >.05; Vmax/Km, 5.7 +/- 1.2 vs 6.1 +/- 0.9; P >.05). These results demonstrate that reduction of CsA dose in combination with MMF may improve the kinetics of Na/LiCT and lessen the long-term side effects of CsA without increasing the risk of rejection.

High prevalence of hepatitis G viremia among kidney transplant patients in Thailand.

Patients receiving kidney transplants (KT) are at high risk for blood borne viral infections. To determine the prevalence of a recently discovered hepatitis G virus (HGV) in this patient group, reverse transcription-polymerase chain reaction (RT-PCR) employing primers derived from the NS5 region of the viral genome was utilized. HGV RNA was detected in 40 of 94 KT patients (43%), as compared to 3 of 69 healthy subjects (4.3%). Cocirculation of HGV and hepatitis C virus (HCV) RNA was detected in 12 patients (13%). Comparison of patients with and without HGV revealed that the former had received hemodialysis before transplantation for a significantly longer duration than the latter (28 vs. 17 months, respectively; P < 0.05). The amount of blood transfused and mean levels of liver enzymes, including alkaline phosphatase, alanine transaminase, and aspartate transaminase, were the same in both groups. Sequence analysis of 275-base pair DNA clones obtained from 2 patients revealed approximately 92% sequence homology to the published HGV and GB virus C sequences. These results suggested that HGV infection among Thai KT patients was high and the role of HGV in causing liver disease remains to be determined.

Lupus nephritis in Thailand: clinicopathologic findings and outcome in 569 patients.

The prognosis of lupus nephritis patients in Thailand has been reported to be poorer than that in Western countries since 1978. After a great evolution in management, we re-evaluate the long-term outcome in patients who were treated and followed up at Siriraj Hospital in Bangkok from 1984 to 1991. Clinical and pathologic records were collected from 569 patients (515 females and 54 men) who were followed up for a mean period of 38.7 +/- 34.6 months. The mean age was 28 +/- 10 years and the median duration of symptoms prior to admission was 7 months. Hypertension was diagnosed in 32.4% of patients and 41.3% had serum creatinine greater than 1.5 mg/dL. Nephrotic-range proteinuria was found in 43.6% of patients and creatinine clearance less than 50 mL/min was found in 58.0%. Of the 314 patients who underwent renal biopsy, the most common histologic finding was diffuse proliferative glomerulonephritis (61.5%). The overall probability of survival was 76.5% at 60 and 90 months after diagnosis. Initial presence of hypertension, renal insufficiency (creatinine clearance < 25 mL/min), and World Health Organization histology class IV and III in the biopsied patients were the three independent factors significantly associated with lower survival probability. Neither gender nor amount of proteinuria was the predictive factor for poor outcome. During the follow-up period, 89 patients died and two patients entered a chronic dialysis program. The two leading causes of death were infection (50.5%) and uremia (28.6%).(ABSTRACT TRUNCATED AT 250 WORDS)