[Show abstract][Hide abstract] ABSTRACT: Kidney anion exchanger 1 (kAE1) plays an important role in acid-base homeostasis by mediating chloride/bicarbornate (Cl−/HCO3−) exchange at basolateral membrane of α-intercalated cells in distal nephron. Impaired intracellular trafficking of kAE1 caused by mutations of SLC4A1 encoding kAE1 results in kidney disease – distal renal tubular acidosis (dRTA). However, it is not known how the intracellular sorting and trafficking of kAE1 from trans-Golgi network (TGN) to the basolateral membrane occur. Here, we studied the role of basolateral-related sorting proteins, including mu1 subunit of adaptor protein (AP) complexes, clathrin, and protein kinase D, on kAE1 trafficking in polarized and non-polarized kidney cells. By using RNA interference, co-immunoprecipitation, yellow fluorescent protein-based protein fragment complementation assay, and immunofluorescence staining, we demonstrated that AP-1 mu1A, AP-3 mu1, AP-4 mu1 and clathrin (but not AP-1 mu1B, PKD1 or PKD2) play crucial roles in intracellular sorting and trafficking of kAE1. We also demonstrated co-localization of kAE1 and basolateral-related sorting proteins in human kidney tissues by double immunofluorescence staining. These findings indicate that AP-1 mu1A, AP-3 mu1, AP-4 mu1, and clathrin are required for kAE1 sorting and trafficking from TGN to the basolateral membrane of acid-secreting α-intercalated cells.
[Show abstract][Hide abstract] ABSTRACT: Patients with diffuse proliferative lupus nephritis (class IV) who responded to treatment within 6 months had better renal outcome than those who did not. Glomerular macrophage is known to be associated with poor renal outcome in glomerular diseases.
To evaluate association between glomerular macrophage number and early treatment response in lupus nephritis class IV patients.
Renal biopsies (n = 90, 86 females) diagnosed with lupus nephritis class IV were included in the study. The patients were divided into 2 groups (n = 45 each) according to response to treatment within 6 months. The treatment response group was defined as having decreased serum creatinine at least 25% from baseline and 24 hr urine protein or UPCR (urine protein creatinine ratio) < 1. The non-response group was defined as stable or increased serum creatinine and 24 hr urine protein or UPCR > or = 1. Immunohistochemistry for macrophage marker (CD68) was performed and the glomerular macrophages were counted on each biopsy. The relevant clinicopathologic data were collected.
The glomerular macrophage number in response and non-response group was 4.5 +/- 2.5 and 6.2 +/- 4.5 respectively (p = 0.029). The glomerular macrophage number was conversely and inversely correlated with activity (r = 0.281, p = 0.007) and chronicity (r = -0.358, p < 0.001) index, respectively
Lupus nephritis class IV patients who responded to treatment within 6 months had lower glomerular macrophages than those who did not. The glomerular macrophage number may be used to determine treatment response in lupus nephritis class IV patients.
Journal of the Medical Association of Thailand = Chotmaihet thangphaet 02/2013; 96 Suppl 2:S246-51.
[Show abstract][Hide abstract] ABSTRACT: Lupus nephritis (LN) is uncommon after the age of 50 years and studies of elderly patients with LN are rare. The authors conducted the current study to determine the clinical manifestations, pathological features and prognosis of 30 Thai patients with late onset LN in Siriraj hospital in Bangkok from 1989 to 2006.
Thirty LN patients with a disease onset beyond the age of 50 years from 1989 to 2006 were enrolled in this retrospective study. All of them received renal biopsy. The histological classifications were categorized according to 2003 International Society of Nephrology/Renal Pathology Society (ISN/RPS) classification.
Clinical and pathologic records were collected from 30 patients (23 female and 7 men) who were followed-up for a mean period of 25.8 months (range, 6 to 96 months). The mean age was 56.6 +/- 4 years. Hypertension was diagnosed in 66.7% of patients and 41.3% had serum creatinine greater than 1.5 mg/dL. Nephrotic-range proteinuria was found in 63.3% of patients and creatinine clearance less than 50 ml/min was found in 70%. Of the 30 patients, the most common renal histologic finding was diffuse proliferative glomerulonephritis (63.30%). The overall probability of patient survival was 94.1% at 12 months, 68.6% at 36 months and 34.3% at 60 months. During the follow-up period (25.8 months; range, 6 to 96 months), 4 patients died. Infection was the leading cause of death (75%).
Lupus nephritis in the elderly patients is not uncommon. Prompt diagnosis should be made for appropriate management and optimal outcome.
Journal of the Medical Association of Thailand = Chotmaihet thangphaet 02/2012; 95 Suppl 2:S213-7.
[Show abstract][Hide abstract] ABSTRACT: Impaired trafficking of human kidney anion exchanger 1 (kAE1) to the basolateral membrane of α-intercalated cells of the kidney collecting duct leads to the defect of the Cl(-)/HCO(3)(-) exchange and the failure of proton (H(+)) secretion at the apical membrane of these cells, causing distal renal tubular acidosis (dRTA). In the sorting process, kAE1 interacts with AP-1 mu1A, a subunit of AP-1A adaptor complex. However, it is not known whether kAE1 interacts with motor proteins in its trafficking process to the plasma membrane or not. We report here that kAE1 interacts with kinesin family member 3B (KIF3B) in kidney cells and a dileucine motif at the carboxyl terminus of kAE1 contributes to this interaction. We have also demonstrated that kAE1 co-localizes with KIF3B in human kidney tissues and the suppression of endogenous KIF3B in HEK293T cells by small interfering RNA (siRNA) decreases membrane localization of kAE1 but increases its intracellular accumulation. All results suggest that KIF3B is involved in the trafficking of kAE1 to the plasma membrane of human kidney α-intercalated cells.
Biochemical and Biophysical Research Communications 08/2011; 413(1):69-74. · 2.41 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
A retrospective analysis was undertaken in systemic lupus erythematosus patients (n = 150, 44 <15 years old, 106 0e;15 years old) who underwent renal biopsy. The specimens were evaluated for histological features of APSN and other significant clinical parameters. The result of antiphospholipid antibodies, clinical course, and renal function from chart review were analysed.
The prevalence of APSN in systemic lupus erythematosus patients who underwent renal biopsies was 34% (16% in <15-year-old group, 41.5% in > or =15-year-old group). APSN was associated with more severe hypertension (P = 0.002 for systolic and P = 0.004 for diastolic blood pressure), acute renal failure (P = 0.003), persistent heavy proteinuria (P < 0.001 for 4+ proteinuria), severe lupus nephritis (class III and IV, P = 0.014, high activity and chronicity indices, P < 0.001) and a tendency to progress to end-stage renal disease.
Systemic lupus erythematosus patients who underwent renal biopsies in our institute showed a prevalence of APSN comparable to those in western countries. The presence of APSN was significantly higher in the adult than in the paediatric population. Its association with poor prognostic indicators suggests poor renal outcome. Clinicians should be aware of this condition in order to give proper care to systemic lupus erythematosus patients.