Paisal Parichatikanond

Identification of human urinary trefoil factor 1 as a novel calcium oxalate crystal growth inhibitor

Previous research on proteins that inhibit kidney stone formation has identified a relatively small number of well-characterized inhibitors. Identification of additional stone inhibitors would increase understanding of the pathogenesis and pathophysiology of nephrolithiasis. We have combined conventional biochemical methods with recent advances in mass spectrometry (MS) to identify a novel calcium oxalate (CaOx) crystal growth inhibitor in normal human urine. Anionic proteins were isolated by DEAE adsorption and separated by HiLoad 16/60 Superdex 75 gel filtration. A fraction with potent inhibitory activity against CaOx crystal growth was isolated and purified by anion exchange chromatography. The protein in 2 subfractions that retained inhibitory activity was identified by matrix-assisted laser desorption/ionization-time-of-flight MS and electrospray ionization-quadrupole-time-of-flight tandem MS as human trefoil factor 1 (TFF1). Western blot analysis confirmed the mass spectrometric protein identification. Functional studies of urinary TFF1 demonstrated that its inhibitory potency was similar to that of nephrocalcin. The inhibitory activity of urinary TFF1 was dose dependent and was inhibited by TFF1 antisera. Anti-C-terminal antibody was particularly effective, consistent with our proposed model in which the 4 C-terminal glutamic residues of TFF1 interact with calcium ions to prevent CaOx crystal growth. Concentrations and relative amounts of TFF1 in the urine of patients with idiopathic CaOx kidney stone were significantly less (2.5-fold for the concentrations and 5- to 22-fold for the relative amounts) than those found in controls. These data indicate that TFF1 is a novel potent CaOx crystal growth inhibitor with a potential pathophysiological role in nephrolithiasis.

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)

Prevalence and clinicopathologic findings of antiphospholipid syndrome nephropathy in Thai systemic lupus erythematosus patients who underwent renal biopsies.

Aim:  To determine the prevalence of antiphospholipid syndrome nephropathy (APSN) in Thai systemic lupus erythematosus (SLE) patients who underwent renal biopsy and to compare the relationship of renal histopathology and other significant clinical parameters between SLE patients with and without APSN.

RENAL FAILURE IN TWO PATIENTS WITH WOLFRAM SYNDROME

We describe a Thai family with three children, two of whom presented with Wolfram syndrome, which is a rare syndrome characterised by diabetes insipidus, diabetes mellitus, optic atrophy, deafness and urinary tract dilatation. A girl and her younger brother had insulin-dependent diabetes mellitus at 11 years old with early onset of renal impairment, proteinuria and hypertension. Urinary tract dilatation was demonstrated in both patients. Kidney biopsies were compatible with diabetic nephropathy. Both children also had bilateral sensorineural hearing loss. Optic atrophy with severe loss of vision was detected in the girl and bilateral cataract in her brother. Both patients were HLA DR2 positive. At 16 years old, her creatinine clearance was 16 ml/min/1.73 m2. Her brothers creatinine clearance was 25 ml/min/1.73 m2 at 13 years old. We conclude that renal function should be evaluated in patients with Wolfram syndrome and the cause of renal failure in these patients may be rapid and severe diabetic nephropathy.

Evaluating the Clinical Course and Prognostic Factors of Posttransplantation Immunoglobulin A Nephropathy

INTRODUCTION Previous reports have suggested that posttransplantation immunoglobulin (Ig) A nephropathy displays a relatively benign course, hardly ever affecting graft function. However, more recent studies with longer follow-up have shown that posttransplantation IgA nephropathy may be a significant contributor to graft loss. Additionally, there may be other clinical or pathological factors that affect long-term graft outcome. We retrospectively analyzed 30 kidney transplant recipients with biopsy-proven IgA nephropathy in their allografts to determine the clinical course and prognostic factors in posttransplantation IgA nephropathy. The median duration of follow-up was 36 months (range, 1 month-17 years). The median onset of IgA nephropathy was 33.6 months posttransplantation (range, 5 days-103 months). The most common presentation was an abnormal urine examination (96.6%). Fifteen (50%) displayed microscopic hematuria with proteinuria more than 1 g/d. Fifteen patients (50%) lost their grafts at a median time of 24 months after the onset of disease (range, 1-93 months). Allograft loss was associated with a high serum creatinine level at the time of diagnosis (3.68 +/- 2.23 vs 1.79 +/- 0.34 mg/dL; P = .006), a greater level of proteinuria at the time of diagnosis (2.43 +/- 0.76 vs 1.29 +/- 1.07 g/d; P = .003), and more than 50% extracapillary proliferation (P = .05). Fibrinoid necrosis on allograft pathology impacted 1-year allograft survival (P = .025). CONCLUSION Posttransplantation IgA nephropathy worsens allograft outcomes among patients with increased serum creatinine level or significant proteinuria at presentation or significant glomerular inflammation and/or tubulointerstitial damage.