Treatment of lupus nephritis and primary glomerulonephritis with enteric-coated mycophenolate sodium.

AIMS: Mycophenolate mofetil is an effective therapy for lupus nephritis (LN) and other glomerulonephritis (GN). However, gastrointestinal (GI) complications can limit its use. Enteric-coated mycophenolate sodium (EC-MPS) has been designed to reduce GI adverse events, but it has not been fully investigated in the treatment of GN. METHODS: Patients with LN and primary GN who had received EC-MPS were studied for effects on renal function. RESULTS: 30 subjects (17 LN, 13 primary GN) were studied. EC-MPS decreased proteinuria in both LN and GN. In LN, 16 patients had EC-MPS as induction therapy. Of these, 8 patients achieved complete remission (CR), 4 had partial remission (PR) and 1 improved renal function. In primary GN, CR was achieved in 4 out of 5 with minimal change disease, but only 1 did not relapse. PR was achieved in 1 of 4 patients with membranous glomerulopathy, 2 out of 2 patients with focal segmental glomerulosclerosis and 1 out of 2 patients with IgA nephropathy. Infections, anemia and alopecia were observed, but no patient had GI side effects. CONCLUSIONS: EC-MPS is effective in LN, but not as effective in primary GN. The risk of GI side effects appears to be low, but other side effects can still occur.

Sirolimus attenuates the rate of progression of early chronic allograft nephropathy.

Optimal treatment for patients with chronic allograft nephropathy (CAN) is not known. Early intervention is preferred. We examined the benefit of adding sirolimus (SRL; C(0) 5-12 ng/mL: HPLC) on the rate of progression of early CAN. We identified patients with biopsy-confirmed Banff grade 1 CAN. After biopsy, patients were switched to SRL + CsA + prednisolone (SRL), MMF + CsA + prednisolone (MMF), or CsA + AZA + prednisolone (AZA). GFR was estimated by Cockcroft-Gault and MDRD formulae. The rate of GFR decline (delta GFR) was determined by calculating the slope of the regression line of estimated GFR (MDRD and Cockcroft-Gault method) at different times. Statistical analysis was performed by the Wilcoxon test. The 41 patients with CAN grade 1 were assigned to SRL: MMF: AZA = 12: 20: 9. Before biopsy; the graft age for SRL: MMF: AZA were 56 +/- 27: 70 +/- 48: 51 +/- 36 months; and the GFR (MDRD method), 38 +/- 8: 42 +/- 15: 36 +/- 14 mL/min; GFR (C-G method) 45 +/- 13, 42 +/- 12, 41 +/- 15 mL/min; trough CsA levels 152 +/- 36: 145 +/- 46: 177 +/- 61 ng/dL; delta GFR (MDRD method) -0.18 +/- 0.20: -0.15 +/- 0.59: -0.20 +/- 1.08; delta GFR (C-G method) -0.13 +/- 0.37: -0.19 +/- 0.24: -0.65 +/- 0.99. Follow-up time for SRL: MMF: AZA was 19 +/- 4: 35 +/- 32: 59 +/- 54 months. At last follow-up; GFR (MDRD method) for SRL: MMF: AZA were 39 +/- 13: 35 +/- 21: 40 +/- 24 mL/min; GFR (C-G method) 46 +/- 17, 37 +/- 18, 46 +/- 25 mL/min; BP 128 +/- 11/79 +/- 7: 131 +/- 22/80 +/- 14: 132 +/- 20/82 +/- 11 mm Hg; and CsA level 52 +/- 25: 122 +/- 41: 155 +/- 49. After biopsy, statin was prescribed in nine SRL, 10 MMF, and three AZA. ACEI was prescribed in two SRL, three MMF, and two AZA. Compared with the prebiopsy values, the delta GFR (MDRD method) changed to -0.04 +/- 0.31 (SRL; P = .04), -0.17 +/- 0.40 (MMF; P = .60), and -0.97 +/- 1.52 (AZA: P = .16). Delta GFR (C-G method) was also significantly improved in the SRL group (-0.02 +/- 0.47; P = .05) but not in the MMF (-0.13 +/- 0.51; P = .53) or AZA (-0.54 +/- 1.78; P = .44). We concluded that patients with early CAN who are switched to SRL and low-dose CsA have a significant attenuation of the rate of GFR declination when compared with patients who receive MMF or AZA addition.

Lupus nephritis: a challenging cause of rapidly progressive crescentic glomerulonephritis.

The outcomes of 32 lupus patients with rapidly progressive crescentic glomerulonephritis were studied. Lupus nephritis accounted for 51.6% (32/62) of all patients with biopsy proven rapidly progressive crescentic glomerulonephritis during a six year observation period that includes 961 consecutive native kidney biopsies. Median entry serum creatinine was 221 micromol/l. All patients received induction therapy with pulse methylprednisolone (n =27) or intravenous cyclophosphamide (n = 5). Maintenance therapies included prednisolone alone (group 1), prednisolone plus intermittent pulse intravenous cyclophosphamide (IVCY) (group 2) and prednisolone plus daily oral cytotoxic drugs (group 3). Twelve patients eventually had uremia. Seven further patients died of infection during therapy. One patient still had renal insufficiency and twelve patients had favorable clinical outcome (serum creatinine < 200 micromol/l). Patients in group 3 were more likely to have favorable clinical outcome than group 2 (P = 0.01; Fisher's exact test). Survival analysis found that the three year survival of 'group 2' was 27.6% while that of 'group 3' was 83.3%. Our results suggest that lupus nephritis is not an infrequent cause of crescentic glomerulonephritis. Therapy with IVCY is not necessary associated with good outcome. Selected patients can be effectively treated with daily oral cytotoxic drugs as a reasonable alternative therapy.

Renal osteodystrophy in Ramathibodi Hospital: histomorphometry and clinical correlation.

UNLABELLED: The spectrum and clinical relevance of renal osteodystrophy in Thai dialysis patients are unknown. A study was conducted on the prevalence and clinico-pathological correlation of renal osteodystrophy in chronic dialysis patients who attended Ramathibodi Renal Transplant Clinic between September 1996 and March 1998. All possible volunteers were enrolled irrespective of musculoskeletal symptoms. Fifty six dialysis patients, including 17 (30.4%) CAPD and 39 (69.6%) hemodialysis patients, participated in this study. Serum calcium, phosphate, iPTH, and bone specific alkaline phosphatase were determined. Transiliac crest bone specimens were measured with an average of 30 fields/specimen by a specific computer program for bone histomorphometry (Osteomeasure), and were also studied for dynamic by double tetracycline label. Bone mineral density (BMD) was also determined by DEXA scan. The type of bone pathology was based on Fournier's criteria for renal osteodystrophy. The mean +/- SEM for age was 45.52 +/- 1.74 years, dialysis duration 42.26 +/- 5.54 (range 1-156) months, calcium phosphate product 52.31 +/- 2.77, and iPTH 307.73 +/- 62.04 pg/ml. The following types of renal osteodystrophy were found: adynamic bone 23 (41.1%), hyperparathyroid 16 (28.6%), mixed type 11 (19.6%), mild lesion 3 (5.4%), osteomalacia 2 (3.6%), and osteosclerosis 1 (1.8%) cases. Two cases of aluminum related bone disease were found. The distribution of different bone diseases was not affected by mode of dialysis or vitamin D supplement, but it was affected by dialysis duration. High turnover bone diseases were associated with longer dialysis duration (63.19 +/- 8.9 vs 23 +/- 4.73 months), higher iPTH (541.53 +/- 109.32 vs 87.77 +/- 15.76 pg/ml), and higher bone specific alkaline phosphatase (25.43 +/- 5.04 vs 9.62 +/- 1.34 mg/ml) when compared to low turnover bone diseases, p < 0.05. Intact PTH of greater than 200 pg/ml was a good predictor for high turnover bone diseases (74% sensitivity and 96% specificity). BMD at torch and wards areas varied inversely with dialysis duration (r = -0.3 and r = -0.4, respectively; p < 0.05). Chronic dialysis patients had a greater tendency of bone loss compared to the general Thai population. There was no difference in BMD between CAPD and hemodialysis patients or different types of bone lesions. CONCLUSION: Significant bone diseases are common among Thai chronic dialysis patients. Adynamic bone disease is the most common bone lesion followed by hyperparathyroid and mixed type. The spectrum of bone diseases is affected mainly by dialysis duration. Intact PTH is a good predictor of high turnover bone disease. Greater bone loss than in the general population is common in our patients and is also accentuated by longer dialysis duration.

Antineutrophil cytoplasmic antibody (ANCA) and rapidly progressive crescentic glomerulonephritis in Thai population.

The impact of vasculitis as a cause of primary rapidly progressive crescentic glomerulonephritis (RPGN) was examined in patients with Thai ethnic by antineutrophil cytoplasmic antibody (ANCA) test. Thirty patients found in a six years study period were included. Patients' mean age was 34.8+/-16.4 years. Mean crescent score was 86.2+/-22.9%. ANCA proved positive in fifteen patients. This helps to differentiate vasculitis associated (ANCA positive) from nonvasculitis (ANCA negative) RPGN. Incidence of immune complex type RPGN (46.6%) is higher than the Caucasians while the incidence of antiglomerular basement membrane antibody (anti-GBM disease) is much lower. More vasculitis patients were treated with cyclophosphamide (n = 11) than the nonvasculitis group (n = 2). Mean renal survival time of ANCA and non-ANCA associated patients were 26.69 and 14.16 months, respectively. Renal survival of all patients is significantly worse if associated with a high entry creatinine (>6 mg/dl). Our results show that vasculitis associated RPGN is not an uncommon disease in the Thai population and can be recognized initially by ANCA test.