[Nephropathy after use of Chinese herbs: rapidly progressive interstitial renal fibrosis or renal vasculitis?]. / Nefropatia po stosowaniu ziól Chinskich: gwaltownie postepujace wlóknienie nerek czy vasculitis nerkowy?

Case of 47 old women with progressive renal failure after chinese herbs and picture of renal interstitial fibrosis in the initial renal biopsy is presented. Pathogenic role of renal limited microscopic vasculitis is discussed on the basis of clinical outcome, high serum levels of p-ANCA as well as complete remission of the disease after long-term cyclophosphamide therapy.

Transplantation of kidneys harvested from non-heart-beating donors: early and long-term results.

The purpose of this retrospective study was to evaluate results of non-heart-beating donor (NHBD) kidney transplantation. Between Jan 1986 and Dec 1994, 80 out of 582 cadaveric kidneys were harvested from NHBD (31.9 min +/- 24 after cardiac arrest). The results in the NHBD group (76 recipients) were compared with those obtained after transplantation of kidneys harvested from heart-beating donors (HBD) with respect to early graft function, and the graft and recipient's survival. Both groups were matched for sex, age, PRA level, number of HLA mismatches, and cold ischemia time. Triple immunosuppression therapy was used in both groups. Acute tubular necrosis (ATN) was observed significantly more frequently in the NHBD group (50 of 76 recipients vs 33 of 100 in the HBD group). The striking finding of this study was that the occurrence of primary non-function was the same in both groups and that the main cause of it was acute rejection. The 1-year patient and graft survival rates were 98.7% and 81.6% for the NHBD group and 99% and 90% for the HBD group, respectively. There was also no statistical difference in the serum creatinine concentration in both groups. We concluded that despite an increased incidence of ATN in the NHBD kidney recipients, the long-term results are good and comparable with those in the HBD group.

Human chronic kidney allograft rejection is accompanied by increased intraglomerular cathepsin B and L activity.

The major reason for late graft losses is chronic rejection. Recently, a large number of studies have indicated that proteolytic enzymes play an important role as mediators of glomerular injury. The cysteine proteinases cathepsins B and L degrade structural matrix proteins such as type I collagen and laminin. We investigated intraglomerular protease activities in 12 patients after kidney graftectomy because of end-stage renal disease following chronic rejection. A group of 12 patients undergoing nephrectomy because of cancer served as controls using only non-involved parts of the kidney. The activities of cathepsins B and L in homogenates of isolated glomeruli were measured fluorometrically methylcoumarylamide substrates and related to DNA content. In rejected kidney allografts we observed significantly enhanced intraglomerular cathepsin B activity and cathepsin B + L activity.

Low-dose heparin: a novel approach in immunosuppression.

Very low subcutaneous doses of standard and low molecular weight heparin inhibited the traffic of sensitized lymphocytes to a graft site, reduced in situ mononuclear cell infiltration and prolonged skin allograft survival in mice. Similar effects were caused by low doses of oral heparin, while higher oral doses prolonged graft survival. Our results suggest that oral heparin may have immunosuppressive properties applicable in clinical transplantation.

Low dose heparin: efficacious treatment for chronic renal allograft rejection.

Recent data indicate that aside from its anti-coagulant action heparin has potent immunobiological activities inhibiting cell trafficking to a site of antigen. In addition, heparin inhibits smooth muscle cell proliferation and decreases the synthesis of the extracellular matrix proteins. As those phenomena are thought to play a major role in the pathogenesis of chronic allograft rejection, we performed a trial evaluating the efficacy of low dose heparin (5 U/kg/day) in 23 recipients of renal allografts with biopsy-proven rejection. In 16 patients (70%) a tendency for improvement was seen which in 57% was statistically significant. Our data suggest that low dose non-anticoagulant heparin may be an efficacious means for treatment of chronic rejection.

Effect of enalapril on proteinuria after kidney transplantation.

We studied the effect of enalapril, an inhibitor of angiotensin-converting enzyme (iACE), on proteinuria and renal function in recipients of renal allografts. Twenty-two patients with post-transplant nephrotic syndrome were treated with incremental doses of enalapril for 1 year. Urinary protein excretion decreased after 2 months of treatment from a mean of 8.9 g/day (range 4.0-18.9 g/day) to 4.5 g/day (range 0.4-10.0 g/day; P < 0.01) and remained significantly low for the rest of the study. However, in the same period, creatinine clearance did not change significantly; it went from 47.8 ml/min (range 17.1-110.3 ml/min) before treatment to 44.2 ml/min (range 16.5-88.5 ml/min) after 2 months of iACE therapy. Analysis of individual data showed that there was a significant reduction in proteinuria in 14 of the 22 patients and that the rate of deterioration of renal function did not increase in 17 of the 22 patients. We did not observe any serious side effects of enalapril administration. The results of our study prove that iACE can be used safely and effectively to reduce post-transplant proteinuria.

Immune monitoring after renal transplantation. II. Post-transplant disturbances in the CD3 complex expression may be caused by immunosuppression.

The in vitro effect of major immunosuppressive agents on the CD3-TCR complex expression on T cells was studied. Cyclosporine and azathioprine caused a marked diminution of alpha/beta, but not gamma/delta and CD3 chains detectability. Prednisolone effect was less manifested. Our data suggest that the reported decrease in alpha/beta chains expression on T cells from renal allograft recipients may be caused by post-transplant immunosuppression.

Immune monitoring after renal transplantation. I. HLA-D expression on T cells from renal allograft recipients.

The expression of class II antigens (HLA-DR, DP and DQ) on resting and PHA-activated T cells from renal allograft recipients was studied. A tendency for increase in DR+/DQ+ T cells was noted in azathioprine and cyclosporine-treated recipients undergoing rejection. Low inducible HLA-D expression (especially DP) was associated with CMV infection. Cyclosporine (but not azathioprine) lowered the rate of synthesis of HLA-D by T cells activated in vitro.

Rejection-associated upregulation of the alpha/beta-T cell receptor expression on T cells of renal allograft recipients.

Peripheral T lymphocytes of renal allograft recipients were phenotyped for their expression of the CD3-T cell receptor (TCR) complex. The majority of T cells from patients with stable graft function had normal CD3 but diminished TCR alpha/beta heterodimer expression, while TCR gamma/delta + T cells were increased in some cases. Acute rejection was associated with an increase in TCR alpha/beta + T cells to normal levels.

IgA nephropathy: a long-term progressive study.

Thirty-three cases of idiopathic IgA nephropathy were followed up for an average of 90.8 +/- 8.4 months. Four therapeutic regimens were applied: symptomatic therapy, immunosuppressive drugs, dipyridamole with acetylsalicylic acid and immunomodulating treatment with thymosin. Parameters of kidney function obtained during control and treatment periods were compared in each patient separately. In all cases but one, frequent fluctuations of serum creatinine levels were observed. Cumulative kidney survival ratio for 5, 10 and 15 years amounted to 1.00, 0.90 and 0.82, respectively. There was no apparent response to thymosin, aspirin and dipyridamole therapy. Immunosuppressive drugs are recommended in cases with steadily progressive disease, when serum creatinine concentration surpasses 2.5 mg/dl.

Long-term immunosuppressive therapy of idiopathic membranoproliferative glomerulonephritis.

Fifty cases of idiopathic membranoproliferative glomerulonephritis were followed up for an average of 10 +/- 0.9 (SE) years. Forty of them, who presented a nephrotic syndrome, were treated by immunosuppressive drugs (prednisone, azathioprine, chlorambucil, cyclophosphamide) for 79 +/- 9.7 (SE) months. Cumulative survival ratio for 5, 10 and 15 years after enrollment was 0.90, 0.82 and 0.77 and after appearance of first symptoms or signs of kidney disease as determined by anamnestic data 0.97, 0.91 and 0.90 accordingly. Triple-drug therapy (prednisone and azathioprine combined with chlorambucil or cyclophosphamide) was more effective in improving proteinuria than other immunosuppressive regimens. No serious side effects were encountered.