Renal failure in multiple myeloma: presenting features and predictors of outcome in 94 patients from a single institution

BACKGROUND: Twenty percent of patients with multiple myeloma (MM) have renal failure. OBJECTIVE: To analyze the presenting features, the response to therapy, and the factors associated with renal function recovery and survival in 94 patients with MM and renal failure. PATIENTS AND METHODS: Medical records of patients from our institution with MM and renal failure diagnosed between January 1969 and December 1994 were reviewed. The statistical methods consisted of Kaplan-Meier survival curves, the log-rank test, logistic regression analysis, and the Cox proportional hazards model for survival analysis. RESULTS: Renal failure was observed in 94 (22.2%) of 423 patients. Patients with renal failure had more advanced disease than the others. Patients with renal failure had a lower response rate to chemotherapy than those with normal renal function (39% vs 56%; P<.001). However, when patients dying within the first 2 months of treatment were excluded, no significant differences in the response rate were found between patients with renal failure and those with normal renal function. Renal function recovery was observed in 26% of patients. Serum creatinine level (<354 micromol/L [<4 mg/dL]), serum calcium level (> or =2.88 mmol/L [> or = 11.5 mg/dL]), and amount of proteinuria (< 1 g/24 h) were associated with renal function recovery. Patients who recovered renal function had a median survival of 28 months vs 4 months for those with nonreversible renal failure (P<.001). In the multivariate analysis, only serum creatinine level (P=.003) and response to chemotherapy (P<.001) were correlated with survival. CONCLUSIONS: Renal failure was present in almost one fourth of patients with MM. Patients with reversible renal failure had longer survival than those not recovering renal function. When patients dying within the first 2 months of treatment were excluded, the response rate was not affected by renal function. Factors associated with renal function recovery were degree of renal failure, presence of hypercalcemia, and amount of proteinuria. Response to chemotherapy and severity of renal failure were the only independent factors associated with survival.     

A multicenter randomized Phase II trial of granulocyte-colony stimulating factor-supported, platinum-based chemotherapy with flexible midcycle cisplatin administration in patients with advanced ovarian carcinoma. PSAMOMA Cooperative Group, Spain

BACKGROUND: The purpose of this study was to analyze whether the addition of granulocyte-colony stimulating factor (G-CSF) to platinum-based combination chemotherapy could increase platinum dose intensity and response rates and decrease hematologic toxicity in patients with advanced epithelial ovarian carcinoma. METHODS: Patients with untreated advanced ovarian carcinoma (International Federation of Gynecology and Obstetrics [FIGO] Stage IIC-IV) were treated after maximum debulking surgery with cyclophosphamide, 750 mg/m2, and carboplatin, 350 mg/m2, on Day 1 plus cisplatin, 75 mg/m2, on Day 14 when clinically indicated (adequate bone marrow and renal function). Patients were randomized to receive chemotherapy alone (Arm A) or chemotherapy supported with G-CSF (5 microg/kg subcutaneously on Days 2-13; Arm B). RESULTS: Between November 1993 and April 1995, 80 patients were included. Seventy-eight patients were evaluable for dose intensity calculations. Both groups were well matched with regard to age, Eastern Cooperative Oncology Group performance status, histopathologic subtype, tumor grade, FIGO stage, and residual tumor after surgery. The dose intensities calculated in mg/m2/week for cyclophosphamide and carboplatin were similar in both groups; however, the dose intensity of cisplatin was higher in Arm B (5.7 mg/m2 vs. 10.3 mg/m2). The occurrence of Common Toxicity Criteria Grade 3-4 neutropenia was less common in the G-CSF arm (55% vs. 7.7%). Response rates (52% vs. 68%) and pathologic complete responses (32% vs. 25%) were similar in both groups. CONCLUSIONS; The addition of G-CSF to this platinum-based chemotherapy regimen in patients with advanced ovarian carcinoma resulted in a modest increment in platinum dose intensity and appeared to reduce the incidence of Grade 3-4 neutropenia.     

难治性淋巴瘤患者外周血T淋巴细胞亚群与自然杀伤细胞活性的检测及其临床意义

目的 探讨外周血T淋巴细胞亚群及自然杀伤(NK)细胞活性水平与难治性淋巴瘤的相关性.方法 采用流式细胞术(FCM)检测60例初治淋巴瘤患者化疗前外周血T淋巴细胞亚群水平与NK细胞的活性,化疗后随访分为难治组30例、有效组30例,以20名健康者为健康对照组.结果 淋巴瘤患者组化疗前外周血CD+4、CD+4/CD+8、NK细胞数比健康对照组低(30.17±8.63与46.52±1.39,t=12.218,P＜0.05;0.86±0.45与1.64±0.05,t=11.225,P＜0.05;12.39±7.08与19.29±0.84,t=6.365,P＜0.05),CD+3、CD+8细胞数比健康对照组高(76.14±10.71与70.48±1.44,t=-3.439,P＜0.05;40.28±14.03与28.35±0.73,t=-5.625,P＜0.05).难治组化疗前外周血CD+4、CD+4/CD+8、NK细胞数比有效组低(27.70±7.81与33.13±8.82,t=2.163,P=0.036;0.67±0.27与1.10±0.52,t=3.272,P=0.003;9.87±6.60与15.40±6.58,t=2.771,P=0.008),而CD+3、CD+8细胞数比有效组高(79.67±8.18与71.91±12.00,t=-2.540,P=0.015;44.70±13.99与34.98±12.41,t=-2.416,P=0.020).结论 淋巴瘤初治患者化疗前外周血T淋巴细胞亚群水平及NK细胞活性的检测,对判断、预测容易转归为难治的患者可能有一定的参考价值.     

Risk factors for contrast nephropathy in diabetic patients undergoing cardioangiography

Risk factors for contrast nephropathy were prospectively studied in 17 patients with non-insulin dependent diabetes mellitus undergoing cardioangiography. Contrast nephropathy, defined as a serum creatinine increase of greater than 25% at 3 day after angiography, occurred in 29.4% of diabetic patients. Patients who developed contrast nephropathy had significantly higher serum creatinine (Cr), fractional excretion of sodium (FENa), urinary albumin excretion rate (AER), and lower 24hr Ccr than patients who did not (Cr: 1.5 +/- 0.3 mg/dl vs. 0.8 +/- 0.1 mg/dl, FENa: 1.9 +/- 0.5% vs. 0.6 +/- 0.1%, AER: 522 +/- 335 micrograms/min vs. 27 +/- 13 micrograms/min, 24hr Ccr: 39.1 +/- 11.6 ml/min vs. 86.2 +/- 9.3 ml/min, P < 0.05). Contrast nephropathy developed in all of two patients with overt proteinuria (AER more than 200 micrograms/min), but none of eight patients with normoalbuminuria (AER below 15 micrograms/min). Three of seven patients with microalbuminuria developed contrast nephropathy, and two of them had advanced nephropathy. FENa obtained next day was significantly elevated over baseline in patients with contrast nephropathy (1.9 +/- 0.5% vs. 9.7 +/- 4.5%, P < 0.05), but unchanged in patients without contrast nephropathy. The rise in C beta 2-microglobulin/Ccr and enzymuria was noted in both group. Percentage decrease of Ccr on the next day was positively correlated with FENa before angiography (r = 0.645, p < 0.01). Of 24hr Ccr, AER, and FENa before angiography, FENa was revealed as a statistically significant discriminant factor for contrast nephropathy by stepwise discriminant analysis (p = 0.0008). These results suggest that contrast nephropathy develops predominantly in the stage not of incipient but of overt diabetic nephropathy indicated by a decline of glomerular filtration, overt proteinuria, and tubular dysfunction. Of them, tubular dysfunction may be the most important risk factor for contrast nephropathy.     

A phase 2 trial of ifosfamide/mesna as salvage therapy in patients with ovarian cancer refractory to or relapsing after prior platinum-containing chemotherapy

Continuous 24-hr infusion of ifosfamide (IFX) with mesna was studied in 19 patients with advanced epithelial ovarian cancer refractory to or recurrent after platinum-containing chemotherapy. The patients received IFX 5 g/m2 as a 24-hr i.v. infusion. Mesna (total dose 8 g/m2) was given i.v. 3 hr before, together with, and 0 and 6 hr after IFX infusion, respectively. Cytotoxic therapy was repeated every 4 weeks. Of 19 evaluable patients, none achieved a complete response, 2 showed a partial response, and 8 had stable disease. Median survival for all patients was 6 months, and median time to progression was 4 months. Toxicity was moderate. Leucopenia WHO grade III-IV was observed in 3 patients. Thrombocytopenia WHO grade III-IV was not observed. Nausea/vomiting WHO grade III-IV occurred in 8 patients. One patient experienced mild reversible confusion. No patients had macro-or microscopic hematuria and there was no deterioration of renal function. We conclude that IFX given as a 24-hr infusion is moderately well tolerated, but has only limited activity in patients with ovarian cancer refractory to or relapsing after prior platinum-containing chemotherapy.     

低剂量辐射对环磷酰胺化疗毒性作用的影响

Objective:The aim of the study was to investigate the effects as well as the possible mechanisms of low dose y-ray pre-irradiation on hepatic damage, DNA damage of peripheral lymphocytes and genetic material damage caused by high dosage of cyclophosphamide (CTX). Methods: Kunming strain male mice were randomly divided into five groups:control group, sham-irradiated group, low dose irradiation group (LDR group), cyclophosphamide chemotherapy group (CTX group) and low close irradiation combined with chemotherapy group (LDR + CTX group). Having being raised for one week,all the mice were implanted subcutaneously with S180 cells in the left inguen (control group excluded). On days 8 and 11,mice of LDR and LDR + CTX groups were given 75 mGy whole-body y-irradiation, 30 h later mice of CTX and LDR + CTX groups were injected I.p. 3.0 mg cyclophosphamide. All the mice were sacrificed on day 13. DNA damage of the peripheral lymphocytes was analyzed using single cell gel electrophoresis (SCGE); ALT activity, total protein (TP) and albumin (ALB)of the plasma were analyzed using automatic biochemistry analyzer; MDA content, SOD and GSH-PX activity of the hepatic homogenate were analyzed using chromometry; genetic material damage was analyzed using micronucleus frequency (MNF)of polychromatoerythrocytes (PCE) in bone marrow. Results: 1. Differences of MDA contents, SOD and GSH-PX activity of hepatic homogenate between 5 groups had notable statistical significance (P < 0.01); in control group MDA content was the lowest, SOD and GSH-PX activity were the highest, while in CTX group MDA content was the highest, SOD and GSH-PX activity were the lowest; compared with CTX group MDA content decreased significantly (P < 0.01) and SOD and GSH-PX activity increased significantly (P <0.05) in LDR + CTX group. 2. Differences of ALT activity of plasma between 5 groups had no statistical significance (F = 1.262, P > 0.05). Differences of TP and ALB of plasma between 5 groups had statistical sig-nificance (F = 12.879 and 6.336 respectively, P < 0.01); TP and ALB in control group were higher than those of other groups and compared with sham-irradiated group, TP and ALB in LDR group elevated significantly (P < 0.05). 3. Differences of DNA damage of peripheral lymphocytes had notable statistical significance (F = 6.383, P < 0.01); DNA damage in control group was the lightest, while DNA damage in CTX group was the severest; compared with CTX group, DNA damage in LDR + CTX group was much lighter (P < 0.05). 4. MNF of PCE between 5 groups had remarkable significance (F = 179.652, P < 0.01);compared with control group and sham-irradiated group, MNF in CTX group increased significantly (P < 0.01); compared with CTX group, MNF in LDR + CTX group had a tendency of decline, which had no statistical significance (P > 0.05). Conclusion:1. CTX can damage the hepatic tissue through oxidative stress; 75 mGy y-irradiation before CTX chemotherapy can induce activities of anti-oxidative enzymes, promote elimination of free radicals, so as to alleviate the damaging effects of oxidative stress to hepatic tissue caused by high-close chemotherapy. 2. A 75 mGy y-irradiation before CTX chemotherapy has no obvious effect on ALT activity of plasma, but may have protective effect on the protein synthesis function of liver. 3. High-close CTX chemotherapy can cause DNA damage of peripheral lymphocytes; 75 mGy y-irradiation before chemotherapy may have certain protective effect on DNA damage. 4. CTX has potent mutagenic effect, can cause significant increase of MNF of PCE;75 mGy y-ray pre-irradiation did not show obvious protection against genetic toxicity of high-dose CTX chemotherapy.     

Cisplatin nephrotoxicity: a multivariate analysis of potential predisposing factors

STUDY OBJECTIVE: To evaluate the usefulness of biologic and pharmacologic parameters for early identification of cisplatin-induced renal dysfunction. DESIGN: Prospective evaluation of 62 consecutively admitted patients with cancer. SETTING: Cancer center. PATIENTS: Sixty-two consecutive patients with cancer (52 men, 10 women; mean age 61.9 yrs). INTERVENTIONS: Patients received cisplatin as a single short intravenous infusion every 3 weeks. One hundred twenty-one cycles were analyzed. The dosage in the first cycle ranged between 61 and 105 mg/m2 (mean 84 mg/m2). All patients received a standard hydration protocol. MEASUREMENTS AND MAIN RESULTS: Renal function was evaluated for each cycle before treatment (day 0) and before next cycle (day 21) based on the estimated creatinine clearance (Clcr). For each cycle, the weighted relative decrease (WD) of Clcr was calculated (WDClcr = 100 x [Clcr (day 0) - Clcr (day 21)]/[Clcr (day 0)](2). Total and ultrafilterable (UF) platinum were measured as a single-sample assay taken 16 hours after the end of cisplatin administration. The mean WDClcr was 0.07 min/100 ml (range -1.0 to +1.7 min/100 ml). The intensity of renal dysfunction evaluated by WDClcr was independent of cisplatin dosage, age, sex, body surface area, initial Clcr, and cycle number. Of interest, total and UF platinum concentrations were significantly correlated to WDClcr: the higher the platinum concentration, the greater the intensity of renal dysfunction. In stepwise regression analysis, UF platinum concentration was the only selected factor. The best prediction of UF platinum was obtained by stepwise regression including cisplatin dosage, initial Clcr, and cycle number (r=0.58, p<0.0001). CONCLUSION: We consider our results to be a first step toward a clinical strategy to identify patients at risk for renal dysfunction after cisplatin treatment.     

Unsatisfactory results of a first-generation modular femoral stem implanted without cement. A 4- to 9-year follow-up study

In a attempt to clarify the effects of methylprednisolone pulse therapy on the insidious (subacute) type of crescentic glomerulonephritis with slow, but steady deterioration of renal function and poor response to treatment, we analyzed the clinical course of 24 patients (male:female = 15:9) with a mean age of 48.5 years. They fulfilled the following criteria: 1) crescents were observed in more than 50% of the glomeruli, 2) the increment of serum creatinine (Cr) could be determined sequentially on three or more occasions before treatment, and reciprocals of serum Cr declined with slopes of less than 1.0 x 10(-2) dl/mg/day, 3) corticosteroids and/or immunosuppressants were administered. The patients were divided into two groups: pulse therapy group (P) (15 patients), to which methylprednisolone 500 or 1,000 mg a day was administered intravenously for three consecutive days, and a conventional therapy group (C) (9 patients). There were no differences between groups P and C in clinical parameters, including sex, age, underlying diseases, urinary protein, blood pressure, serum Cr and slope of 1/Cr before treatment, and pathological findings, including percentages of glomeruli with crescents and degree of interstitial lesions. However, improvement of serum Cr, which was defined as a decline to the normal range or less than half of the pretreatment level, was observed in 9 (60%) in group P vs. only 1 (11%) in group C (p < 0.05). Re-biopsies were performed after treatment in 6 patients of group P with an improvement of serum Cr, and showed a decrease in the rate of crescent formation and almost complete loss of cellular crescents. At 1, 2 and 3 years follow-up, the renal survival rates were 86, 70 and 53%, respectively, in group P vs. 67, 14 and 14% respectively, in group C (p < 0.05). No serious side effects were observed in group P. These results suggest that methylprednisolone pulse therapy may be very effective for the insidious type of crescentic glomerulonephritis.     

BDNF-dependent enhancement of exocytosis in cultured cortical neurons requires translation but not transcription

PURPOSE: The surgical management of chronic atherosclerotic renal artery occlusion (RA-OCC) was studied. METHODS: From January 1987 through December 1996, 397 consecutive patients were treated for atherosclerotic renal artery disease. Ninety-five hypertensive patients (mean blood pressure, 204 +/- 31/106 +/- 20 mm Hg; mean medications, 3.0 +/- 1.1 drugs) were treated for 100 RA-OCCs. Eighty-four (88%) patients had renal dysfunction, defined by serum creatinine levels >/=1.3 mg/dL (mean serum creatinine level, 2.8 +/- 2.0 mg/dL). Demographic characteristics, operative morbidity and mortality, blood pressure/renal function response, and postoperative decline in renal function were examined and compared with that of 302 patients treated for renal artery stenosis (RAS). RESULTS: After operation, there were 5 perioperative deaths (5.2%), 2 (2.8%) after revascularization and 3 (12%) after nephrectomy (P =.11), compared with 12 (4.0%) perioperative deaths in the RAS group (P =.59). After controlling for important covariates, estimated survival and blood pressure benefits did not differ between RA-OCC patients treated by nephrectomy or revascularization (P =.13; 87% vs 92%, P =.54). Excretory renal function was considered improved in 49% of 79 RA-OCC patients with renal dysfunction, including 9 patients removed from dialysis-dependence. Among patients treated for unilateral disease, revascularization for RA-OCC was associated with significant improvement in renal function (P <.01); however, nephrectomy alone did not increase renal function significantly. Improved renal function after operation was associated with a significant and independent increase in survival (P <.01) and dialysis-free survival (P <.01) among patients treated for RA-OCC. In addition, blood pressure benefit, renal function response, and estimated survival did not differ significantly after reconstruction for RA-OCC or RAS. CONCLUSION: Among hypertensive patients treated for RA-OCC, equivalent beneficial blood pressure response was observed after both revascularization and nephrectomy. In patients who underwent bilateral renal artery revascularization, the change in excretory renal function attributable to repair of RA-OCC cannot be defined. In patients treated for unilateral disease, however, improvement in function was observed only after revascularization. Moreover, improved renal function demonstrated a significant and independent association with improved survival. This experience supports renal revascularization in preference to nephrectomy for RA-OCC in select hypertensive patients when a normal distal artery is demonstrated at operation.     

Semi-quantitative assessment of 99Tcm-sestamibi uptake in lung cancer: relationship with clinical response to chemotherapy

The objectives of this study were to measure semi-quantitatively uptake of 99Tcm-sestamibi (99Tcm-MIBI) by tumour tissue in patients with lung cancer and to investigate its relationship with clinical response to chemotherapy. 99Tcm-MIBI single photon emission tomography was performed at the time of diagnosis in 31 patients with biopsy-proven lung cancer (19 small cell carcinomas, 12 non-small cell carcinomas), all of whom were undergoing chemotherapy. Fifteen patients were also investigated 2 weeks after the first and third cycles of chemotherapy. To quantify 99Tcm-MIBI uptake, a tumour/lung (T/L) ratio was calculated for the tomographic slices. The response to chemotherapy was rated as complete remission, partial remission or no remission using dimensional criteria. The results were expressed as the median and inter-quartile range; non-parametric statistical analyses were used. Forty one neoplastic localizations (31 primary tumours and 10 hilar or mediastinal lymph node masses) were assessed. The median T/L ratio of the primary tumours was 1.85 (range 1.7-2.4). Patients with a different response to chemotherapy had a significantly different median T/L ratio before chemotherapy: complete remission (n = 8), T/L ratio = 2.95 (range 2.20-3.25); partial remission (n = 10), 2.15 (range 1.77-2.40); no remission (n = 13), 1.70 (range 1.47-1.75) (Kruskal-Wallis, P < 0.0001). A T/L ratio of 1.80 gave sensitivity of 83%, specificity of 85% and accuracy of 84% in the prediction of the response to chemotherapy. The patients with small cell carcinomas demonstrated greater 99Tcm-MIBI uptake than those with non-small cell carcinomas: T/L ratio, median 2.30 (range 1.76-3.00) vs 1.70 (range 1.50-1.78) (Mann-Whitney U-test, P = 0.001). No significant difference in 99Tcm-MIBI uptake was observed between the 10 lymph node metastases and the corresponding primary tumours: T/L ratio, median 2.30 (range 1.75-2.50) vs 2.15 (1.77-3.00) (Wilcoxon's paired samples rank test, N.S.). Of the 15 patients who were monitored with scintigraphy during chemotherapy, 10 showed complete or partial remission and a parallel reduction in their T/L ratio. The other five patients showed no response to chemotherapy and their T/L ratio was either unaffected or increased. We conclude that the semi-quantitative assessment of 99Tcm-MIBI uptake may have a significant role to play in the management of lung cancer, providing an effective means of predicting the efficacy of chemotherapy and of selecting subgroups of patients requiring radiotherapy or combined protocols before the start of treatment. 99Tcm-MIBI imaging may also be of use in monitoring clinical response to chemotherapy.