Figure 6.
Effect of bortezomib (Bz)/cyclophosphamide–based therapy on survival, renal lesions, and function of kF-DH mice. Serum LC levels (µg/mL) (A) and serum creatinine levels (B) in treated (n = 6) and nontreated (n = 7) κF-DH mice during 8 weeks of treatment. Note the absence of kidney dysfunction in treated mice. Statistics at day 54 compared end of treatment or euthanization with day 0. (C) Kaplan-Meier overall survival analysis of nontreated vs treated kF-DH mice during 8 weeks of treatment (from age 6-8 months). Note that none of the treated mice died during the course of treatment, whereas half of the nontreated control mice died. Results are from 2 independent experiments. (D) Lesion analysis of kidney sections by immunofluorescence microscopy (top), light microscopy (middle), and electron microscopy (bottom) between κF-DH mice at the beginning of treatment and mice treated/nontreated at the end of treatment. Note that deposits revealed by immunofluorescence in nontreated mice or mice at the beginning of treatment totally disappeared in treated mice. LCDD-suggestive lesions are also absent in treated mice (no glomerulosclerosis or thrombotic microangiopathy–like lesions). Original magnification ×200. (E) Comparison of κ LC deposits in kidneys of κF-DH mice at the age at beginning of treatment (6-month-old kF-DH mice, n = 5) and the kidneys of treated and nontreated mice at the end of treatment. Evaluation of total deposits, glomerular and tubular, were performed with anti-mouse κ LC staining by 4 different experimenters (n = 2 blinded experiments). (F) Urine albumin levels in treated (κF-DH T) and nontreated (κF-DH NT) mice at the end of treatment compared with 6-month-old mice (κF-DH). Survival data were analyzed using log-rank (Mantel-Cox) test, and comparisons between 2 groups were calculated using the nonparametric Mann-Whitney test. Means ± standard error of the mean, and only significant P values are indicated. All statistics at 8 months corresponded to end of treatment or euthanization at humane end point. *P < .05, **P < .01, ****P < .0001; n = 3 mice.

Effect of bortezomib (Bz)/cyclophosphamide–based therapy on survival, renal lesions, and function of kF-DH mice. Serum LC levels (µg/mL) (A) and serum creatinine levels (B) in treated (n = 6) and nontreated (n = 7) κF-DH mice during 8 weeks of treatment. Note the absence of kidney dysfunction in treated mice. Statistics at day 54 compared end of treatment or euthanization with day 0. (C) Kaplan-Meier overall survival analysis of nontreated vs treated kF-DH mice during 8 weeks of treatment (from age 6-8 months). Note that none of the treated mice died during the course of treatment, whereas half of the nontreated control mice died. Results are from 2 independent experiments. (D) Lesion analysis of kidney sections by immunofluorescence microscopy (top), light microscopy (middle), and electron microscopy (bottom) between κF-DH mice at the beginning of treatment and mice treated/nontreated at the end of treatment. Note that deposits revealed by immunofluorescence in nontreated mice or mice at the beginning of treatment totally disappeared in treated mice. LCDD-suggestive lesions are also absent in treated mice (no glomerulosclerosis or thrombotic microangiopathy–like lesions). Original magnification ×200. (E) Comparison of κ LC deposits in kidneys of κF-DH mice at the age at beginning of treatment (6-month-old kF-DH mice, n = 5) and the kidneys of treated and nontreated mice at the end of treatment. Evaluation of total deposits, glomerular and tubular, were performed with anti-mouse κ LC staining by 4 different experimenters (n = 2 blinded experiments). (F) Urine albumin levels in treated (κF-DH T) and nontreated (κF-DH NT) mice at the end of treatment compared with 6-month-old mice (κF-DH). Survival data were analyzed using log-rank (Mantel-Cox) test, and comparisons between 2 groups were calculated using the nonparametric Mann-Whitney test. Means ± standard error of the mean, and only significant P values are indicated. All statistics at 8 months corresponded to end of treatment or euthanization at humane end point. *P < .05, **P < .01, ****P < .0001; n = 3 mice.

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