Jeng Yi Huang

Glomerular Transforming Growth Factor-β1 mRNA as a Marker of Glomerulosclerosis – Application in Renal Biopsies

As transforming growth factor-beta1 (TGF-beta1) is implicated in the pathogenesis of glomerulosclerosis, the aim of the study was to demonstrate if levels of glomerular TGF-beta1 mRNA in renal biopsies correlated with glomerulosclerosis. Glomeruli were collected by microdissection from renal biopsies in patients with membranous nephropathy, lupus nephritis, diabetic nephropathy, minimal change disease and IgA nephropathy presented by proteinuria when serum creatinine was <3 mg%. Glomerular mRNAs were reverse transcribed and TGF-beta1, alpha2(IV) collagen, beta-actin cDNA quantitated by competitive polymerase chain reaction (PCR). By semiquantitative electron microscopy, a 3.5-fold increase of glomerular TGF-beta1/beta-actin mRNA ratio in the moderate sclerotic group (n = 23, p < 0.01) and a 1.5-fold increase in the mild sclerotic group (n = 22, p < 0.05) were observed when compared to the minimal sclerotic group (n = 12). A concordant increase of glomerular alpha2(IV) collagen mRNA was found with 2.2- and 1.3-fold in moderate and mild sclerotic groups, respectively. The TGF-beta1/beta-actin mRNA ratios were highest in membranous nephropathy (466.4 +/- 133.4, n = 11), followed by lupus nephritis (394.9 +/- 94.8, n = 12) and diabetic nephropathy (333.2 +/- 97.6, n = 10). Patients with minimal change disease(233.1 +/- 54.1, n = 15)and IgA nephropathy(185.3 +/- 39.6, n = 9) had low levels. The degree of glomerulosclerosis in each group followed the TGF-beta1/beta-actin mRNA ratios indicating that the level is the major determinant ofglomerulosclerosis but not the disease entities. Glomerular TGF-beta1/beta-actin mRNA ratio did not correlate with clinical parameters such as the urinary protein excretion and creatinine clearance. These results suggest that glomerular TGF-beta1/beta-actin mRNA ratio may be used as a marker of glomerulosclerosis in renal biopsy to reflect the local sclerotic process.

Impact of HCV infection on first cadaveric renal transplantation, a single center experience

Abstract:  Background:  Controversy still persists regarding the impact of HCV infection on renal transplant recipients. This study aimed to evaluate the effect of anti‐HCV antibody status on patients and grafts of renal transplants at a single center.

Osteoporosis After Kidney Transplantation : Preliminary Report From a Single Center

OBJECTIVE One of the major adverse effects of kidney transplantation is osteoporosis, which is mainly related to steroid use. Only limited data are available on calcitonin therapy for posttransplantation osteoporosis. METHOD From March 2007 to August 2007, 67 kidney recipients agreed to enter this study. Dual energy X-ray absorptiometry (DEXA) was performed to evaluate bone mineral density (BMD) in the lumbar (L) spine and left femoral neck. We prescribed calcitonin nasal spray to osteoporosis patients (DEXA T < -2.5 SD) who agreed with the treatment. A second and a third DEXA were performed at 3-month subsequent intervals later to evaluate the therapeutic effects. RESULTS The incidence of osteoporosis in our kidney recipients was 46.26% (31/67 patients). Osteopenia accounted for 38.81% (26/67 patients) and only 14.93% (10/67 patients) were normal. Calcitonin inhalation seemed to improve the BMD with 61% showing improvement on the second DEXA study in our preliminary data. CONCLUSION Our preliminary data suggested that calcitonin may help to restore bone mass in kidney recipients with osteoporosis. Steroid elimination may prevent the onset of osteoporosis and might even enhance calcitonin efficacy. In the future we need a longer study period to confirm the results and compare it with the outcomes of bisphosphonates therapy.

Guillain-Barré syndrome associated with minimal change glomerulopathy and tubular dysfunction: Related to acetone-based organic solvent?

A 55-year-old woman presented with Guillain-Barré syndrome, nephrotic syndrome and multiple tubular dysfunction under occupational exposure to an organic solvent, which contained acetone as the principal solvent. In this case, the onset of the nephrotic syndrome and tubular dysfunction coincided with the development of the neurological manifestation. Renal biopsy demonstrated minimal change glomerulopathy with moderate tubulointerstitial nephritis. Several clearance tests that evaluated tubular transport functions revealed multiple tubular defects (including the Na+-K+-Cl– cotransporter of thick ascending limb and distal proton pump). The simultaneous occurrence of Guillain-Barré and nephrotic syndrome has previously been reported. However, both minimal glomerulopathy with multiple tubular dysfunction and progressive peripheral neuropathy under occupational exposure to an organic solvent remain unreported. Herein, we presented a rare association of minimal change nephrotic syndrome, tubular dysfunction with Guillain-Barré syndrome under the risk of exposure to an acetone-based cleansing solution; the case raises our concerns about possible chronic nephrotoxic or neurotoxic effects of common chemical organic solvents.

Sirolimus conversion experience in a single center.

OBJECTIVE One major cause of graft loss is chronic allograft nephropathy (CAN), which may relate to calcineurin inhibitors (CNIs). We converted CAN cases from CNIs to sirolimus and observed the outcomes. METHOD From January 2004 to August 2007, there were 28 kidney recipients in our center with creeping creatinine levels compatible with CAN. We started sirolimus at 2 mg/d and reduced the CNIs gradually. Sirolimus trough levels were kept between 5 and 8 ng/mL. Mycophenolic acid was cut in half; there was no adjustment on prednisolone dose. RESULTS The mean switch time was 47.3 months after transplantation. One case discontinued sirolimus due to severe drug-induced pneumonitis. Twelve of the 27 (45%) patients showed improvements in graft function. The most frequent complications were anemia (13/28), hyperlipidemia (13/28), and pneumonitis (4/28). A baseline serum creatinine level less than 2.2 mg/dL seemed to forecast a response to sirolimus conversion. Most of the graft functional improvement occurred within 6 months after the switch. No graft or patient loss was encountered. CONCLUSION Our experience suggested that 45% of patients with sirolimus conversion showed improved graft function. Among patients within 1 year after transplantation, those with a creatinine level less than 2.2 mg/dL, no proteinuria, and no hyperlipidemia seemed to be better candidates for Sirolimus conversion.