Long-term followup of patients treated with total lymphoid irradiation for lupus nephritis.

OBJECTIVE: To describe the long-term survival, renal condition, and morbidity outcomes in patients who received total lymphoid irradiation (TLI) for the treatment of lupus nephritis. METHODS: Twenty-one patients with biopsy-proven, diffuse membranoproliferative glomerulonephritis and significant proteinuria of >2.5 grams/day received TLI from 1980 to 1987 at Stanford University Medical Center. All patients had previously failed to respond to treatment with high-dose corticosteroids or therapy with corticosteroids plus immunosuppressive agents (azathioprine, cyclophosphamide, or chlorambucil). RESULTS: The mean duration of followup since TLI was 10.7 years. Fifteen of 21 patients (71%) remained alive at the time of this assessment. Nine of the 21 patients (43%) survived without developing end-stage renal disease (ESRD). The probability of long-term survival without ESRD and without need for additional immunosuppressive agents after TLI was 19% (4 of 21). Factors predicting renal failure at the time of TLI included elevated creatinine levels, increased interstitial fibrosis on renal biopsy, and increased fractional excretion of immunoglobulin and albumin. Malignancies were found in 4 patients, and opportunistic infections occurred in 7 patients. CONCLUSION: Overall, patients with lupus nephritis treated with TLI do not appear to have better 10-year survival with lower incidence of ESRD compared with patients in published series treated with conventional immunosuppressive therapies. However, in this series of patients, treatment with conventional immunosuppressive therapies had been unsuccessful and given the limited number of adverse events and the efficacy seen in some patients, TLI appears to be a reasonable therapeutic option for the treatment of severe lupus nephritis among patients who fail to respond under standard cytotoxic regimens.

Effects of ionizing radiation on progressive experimental renal disease: a hemodynamic approach.

In order to evaluate the progression of renal disease, Munich-Wistar rats were submitted to 5/6 nephrectomy and given whole-body x- or gamma-irradiation with or without remnant kidney protection or were submitted only to remnant kidney irradiation. All groups received a single 6-Gy dose immediately after surgery. Whole-kidney function, glomerular hemodynamics, 24-hour proteinuria and histopathology were assessed 60 days after surgery and irradiation. The irradiated nephrectomized animals presented whole-kidney function parameters comparable to those of normal rats. In addition, they were less hypertensive and had higher hematocrit. They showed glomerular hyperfiltration and hypertension even greater than their respective nephrectomized controls. However, the interrelations among the glomerular filtration determinants were somewhat different in irradiated animals. Their 24-hour proteinuria was significantly lower and the sclerosis index and tubulointerstitial injury score were markedly smaller. Among irradiated animals, the worst sclerosis index was observed in those with a shielded remnant kidney and the best in those without protection of the remnant kidney. This led us to speculate about a possible influence of resident mesangial cells on the early events following renal mass ablation and on the maintenance of subsequent physiopathologic changes. Therefore, radiation undoubtedly provoked a beneficial change in the course of renal disease when the renal mass ablation model was employed. Many factors could have contributed to this favorable feature including lower levels of systemic arterial pressure, less increment in DeltaP, diminished proteinuria, and maintenance of tubulointerstitial space integrity. Our data also suggest that development of glomerulosclerosis seems to be determined by events occurring immediately after injury.

Effectiveness of radiation therapy in nephrotic syndrome associated with advanced lung cancer.

Paraneoplastic nephrotic syndrome is rare, bur occurs mostly in lung cancer. The glomerular lesion usually exhibits membranous nephropathy. Although surgical therapy has been shown to be effective, the treatment of a paraneoplastic nephrotic syndrome has always been a challenge. Currently no standard therapy has been established, if the paraneoplastic nephrotic syndrome is associated with advanced cancer with unresectable lesions. We present 2 cases having paraneoplastic nephrotic syndrome associated with advanced squamous cell carcinoma of the lung. Radiation therapy of the primary tumor effectively caused regression of the paraneoplastic nephrotic syndrome without affecting the renal function. Our results suggest that irradiation can be the first choice in the treatment of nephrotic syndrome, if the primary tumor is unresectable.

Reversal of nzb/nzw disease with total lymphoid irradiation.

NZB/NZW mice spontaneously exhibit autoimmune disease similar to that seen in human systemic lupus erythematosus (SLE). We demonstrated that total lymphoid irradiation (TLI) reversed well expressed disease in 6-mo-old NZB/NZW females with a prolongation in survival, decrease in proteinuria, and decrease in anti-DNA antibodies as compared to control animals. Few side effects were observed in the treated group. TLI also prolonged survival in animals with advanced renal disease. These findings suggest that TLI may have application to the treatment of human SLE.