niacinamide and Proteinuria studies

nicotinamide : A pyridinecarboxamide that is pyridine in which the hydrogen at position 3 is replaced by a carboxamide group.

Proteinuria: The presence of proteins in the urine, an indicator of KIDNEY DISEASES.

Research Excerpts

Excerpt	Relevance	Reference
" Shortly after chemotherapy with sorafenib [anti-vascular endothelial growth factor (VEGF)] was initiated, progressive renal impairment, hypertension, and nephrotic-range proteinuria developed."	7.75	Nephrotic-range proteinuria in a patient with a renal allograft treated with sorafenib for metastatic renal-cell carcinoma. ( Jonkers, IJAM; van Buren, M, 2009)
" Shortly after chemotherapy with sorafenib [anti-vascular endothelial growth factor (VEGF)] was initiated, progressive renal impairment, hypertension, and nephrotic-range proteinuria developed."	3.75	Nephrotic-range proteinuria in a patient with a renal allograft treated with sorafenib for metastatic renal-cell carcinoma. ( Jonkers, IJAM; van Buren, M, 2009)
"Axitinib is a potent and selective second-generation inhibitor of vascular endothelial growth factor receptors 1, 2 and 3."	2.78	Efficacy and safety of axitinib versus sorafenib in metastatic renal cell carcinoma: subgroup analysis of Japanese patients from the global randomized Phase 3 AXIS trial. ( Akaza, H; Chen, C; Kanayama, H; Kim, S; Naito, S; Ozono, S; Shinohara, N; Tarazi, J; Tomita, Y; Tsukamoto, T; Ueda, T; Uemura, H, 2013)
"Recently, cancer therapies have been supplemented by vascular endothelial growth factor (VEGF) inhibitors as anti-angiogenic agents."	2.50	Clinicopathological spectrum of kidney diseases in cancer patients treated with vascular endothelial growth factor inhibitors: a report of 5 cases and review of literature. ( Chandran, CB; Flombaum, CD; Glezerman, IG; Salvatore, SP; Seshan, SV; Usui, J, 2014)
"Angiogenesis does not initiate malignancy but promotes tumor progression and metastasis."	2.44	[Oral drugs inhibiting the VEGF pathway]. ( Armand, JP; Mir, O; Ropert, S, 2007)
"Sorafenib (BAY43-9006) was found to inhibit Raf1, but also VEGFR2 and 3, Flt3, PDGFR-a and b and c-kit, has been tested in a phase III study against placebo after one prior systemic therapy."	2.44	[Angiogenesis and renal cell carcinoma]. ( Billemont, B; Izzedine, H; Méric, JB; Rixe, O; Sultan-Amar, V; Taillade, L, 2007)

Research

Studies (16)

Authors

Clinical Trials (1)

Trial Overview

Trial Outcomes

Duration of Response (DR)

Timeframe	Studies, this research(%)	All Research%
pre-1990	1 (6.25)	18.7374
1990's	0 (0.00)	18.2507
2000's	6 (37.50)	29.6817
2010's	8 (50.00)	24.3611
2020's	1 (6.25)	2.80

Authors	Studies
Wright, MB	1
Varona Santos, J	1
Kemmer, C	1
Maugeais, C	1
Carralot, JP	1
Roever, S	1
Molina, J	1
Ducasa, GM	1
Mitrofanova, A	1
Sloan, A	1
Ahmad, A	1
Pedigo, C	1
Ge, M	1
Pressly, J	1
Barisoni, L	1
Mendez, A	1
Sgrignani, J	1
Cavalli, A	1
Merscher, S	1
Prunotto, M	1
Fornoni, A	1
Wan, RJ	1
Li, YH	1
Ueda, T	1
Uemura, H	1
Tomita, Y	1
Tsukamoto, T	1
Kanayama, H	1
Shinohara, N	1
Tarazi, J	1
Chen, C	1
Kim, S	1
Ozono, S	1
Naito, S	1
Akaza, H	1
Izzedine, H	2
Mangier, M	1
Ory, V	1
Zhang, SY	1
Sendeyo, K	1
Bouachi, K	1
Audard, V	1
Péchoux, C	1
Soria, JC	1
Massard, C	1
Bahleda, R	1
Bourry, E	1
Khayat, D	1
Baumelou, A	1
Lang, P	1
Ollero, M	1
Pawlak, A	1
Sahali, D	2
Usui, J	1
Glezerman, IG	1
Salvatore, SP	1
Chandran, CB	1
Flombaum, CD	1
Seshan, SV	1
Tanaka, Y	1
Kume, S	1
Araki, H	1
Nakazawa, J	1
Chin-Kanasaki, M	1
Araki, S	1
Nakagawa, F	1
Koya, D	1
Haneda, M	1
Maegawa, H	1
Uzu, T	1
Yılmaz, S	1
Özçakar, ZB	1
Taktak, A	1
Kiremitçi, S	1
Ensari, A	1
Dinçaslan, H	1
Yalçınkaya, F	1
Fushima, T	1
Sekimoto, A	1
Oe, Y	1
Sato, E	1
Ito, S	1
Sato, H	1
Takahashi, N	1
Halimi, JM	1
Azizi, M	1
Bobrie, G	1
Bouché, O	1
Deray, G	1
des Guetz, G	1
Lecomte, T	1
Levy, B	1
Mourad, JJ	1
Nochy, D	1
Oudard, S	1
Rieu, P	1
Jonkers, IJAM	1
van Buren, M	1
Kelly, RJ	1
Billemont, B	2
Rixe, O	2
Wu, S	1
Keresztes, RS	1
Ropert, S	1
Mir, O	1
Armand, JP	1
Méric, JB	1
Taillade, L	1
Sultan-Amar, V	1
Patel, TV	1
Morgan, JA	1
Demetri, GD	1
George, S	1
Maki, RG	1
Quigley, M	1
Humphreys, BD	1
Pugliese, G	1
Tilton, RG	1
Speedy, A	1
Chang, K	1
Santarelli, E	1
Province, MA	1
Eades, D	1
Sherman, WR	1
Williamson, JR	1

Trial	Phase	Enrollment	Study Type	Start Date	Status
AXITINIB (AG-013736) AS SECOND LINE THERAPY FOR METASTATIC RENAL CELL CANCER: AXIS TRIAL[NCT00678392]	Phase 3	723 participants (Actual)	Interventional	2008-09-03	Completed
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

DR: time from first documentation of objective tumor response (CR or PR), that was subsequently confirmed, to the first documentation of PD or to death due to any cause, whichever occurred first as per RECIST version 1.0, a) CR: disappearance of all target, non target lesions and no appearance of new lesions, documented on 2 occasions separated by at least 4 weeks, b) PR: at least 30 % decrease in sum of LD of target lesions taking as reference baseline sum of LD, without progression of non target lesions, no appearance of new lesions, c) PD: >=20% increase in sum of LD of the target lesions taking as a reference smallest sum of LD recorded since the start of treatment or unequivocal progression in non-target lesions or appearance of 1 or more new lesions. Occurrence of pleural effusion or ascites if demonstrated by cytological investigation, not previously documented. New bone lesions not previously documented if confirmed by computed tomography/magnetic resonance imaging or X-ray. (NCT00678392)
Timeframe: From initiation of treatment up to follow-up period (up to 3 years)

Objective Response Rate (ORR)

Intervention	Months (Median)
Axitinib 5 mg	11.0
Sorafenib 400 mg	10.6

ORR = percentage of participants with confirmed complete response (CR) or confirmed partial response (PR) according to RECIST version 1.0 recorded from first dose of study treatment until PD or death due to any cause. CR: disappearance of all target, non target lesions and no appearance of new lesions, documented on 2 occasions separated by at least 4 weeks. PR: at least 30 % decrease in sum of LD of target lesions taking as reference baseline sum of LD, without progression of non target lesions, no appearance of new lesions. PD: >=20% increase in sum of LD of the target lesions taking as a reference smallest sum of LD recorded since the start of treatment or unequivocal progression in non-target lesions or appearance of 1 or more new lesions. Occurrence of pleural effusion or ascites if demonstrated by cytological investigation, not previously documented. New bone lesions not previously documented if confirmed by computed tomography/magnetic resonance imaging or X-ray. (NCT00678392)
Timeframe: From initiation of treatment up to follow-up period (up to 3 years)

Overall Survival (OS)

Intervention	Percentage of participants (Number)
Axitinib 5 mg	19.4
Sorafenib 400 mg	9.4

OS was defined as the duration from start of study treatment to date of death due to any cause. OS was calculated as (months) = (date of death minus the date of first dose of study medication plus 1) divided by 30.4. For participants who were alive, overall survival was censored on last date the participants were known to be alive. (NCT00678392)
Timeframe: From initiation of treatment up to follow-up period (up to 3 years)

Progression-Free Survival (PFS)

Intervention	Months (Median)
Axitinib 5 mg	20.1
Sorafenib 400 mg	19.2

PFS was defined as the time in months from start of study treatment to the first documentation of objective tumor progression of disease (PD) or to death due to any cause, whichever occurs first. PD was assessed by response evaluation criteria in solid tumors (RECIST) version 1.0. PD: >=20 percent (%) increase in the sum of the longest dimensions (LD) of the target lesions taking as a reference the smallest sum of the LD recorded since the start of treatment or unequivocal progression in non-target lesions or the appearance of 1 or more new lesions. Occurrence of a pleural effusion or ascites was also considered PD if demonstrated by cytological investigation and it was not previously documented. New bone lesions not previously documented were considered PD if confirmed by computed tomography/magnetic resonance imaging or X-ray. (NCT00678392)
Timeframe: From initiation of treatment up to follow-up period (up to 3 years)

Euro Quality of Life Questionnaire- 5 Dimension (EQ-5D): Health State Profile Utility Score

Intervention	Months (Median)
Axitinib 5 mg	6.7
Sorafenib 400 mg	4.7

EQ-5D: participant rated questionnaire to assess health-related quality of life in terms of a single utility or index score. Health state profile component assesses level of health for 5 domains: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each domain was rated on a 3-point response scale (1= no problems, 2= some/moderate problems and 3= extreme problems). Scoring formula developed by EuroQol Group assigned a utility value for each domain in the profile. Score were transformed and resulted in a total score range of 0 to 1, with higher scores indicating better health. (NCT00678392)
Timeframe: Baseline (Predose on Cycle 1 Day 1) , Day 1 of each cycle until Cycle 21, End of treatment (Day 670) and Follow-up visit (Day 698)

Euro Quality of Life Questionnaire- 5 Dimension (EQ-5D): Visual Analog Scale (VAS)

Intervention	Units on a scale (Mean)
	Baseline (n =347, 341)	Cycle 2/Day1 (n =326, 307)	Cycle 3/Day1 (n =287, 248)	Cycle 4/Day1 (n =262, 226)	Cycle 5/Day1 (n =244, 207)	Cycle 6/Day1 (n =221, 178)	Cycle 7/Day1 (n =213, 163)	Cycle 8/Day1 (n =181, 136)	Cycle 9/Day1 (n =169, 120)	Cycle 10/Day1 (n =151, 98)	Cycle 11/Day1 (n =126, 87)	Cycle 12/Day1 (n =110, 73)	Cycle 13/Day1 (n =96, 61)	Cycle 14/Day1 (n =80, 57)	Cycle 15/Day1 (n =63, 41)	Cycle 16/Day1 (n =54, 37)	Cycle 17/Day1 (n =48, 29)	Cycle 18/Day1 (n =37, 20)	Cycle 19/Day1 (n =29, 14)	Cycle 20/Day1 (n =21, 12)	Cycle 21/Day1 (n =16, 7)	End of Treatment (n =169, 196)	Follow up (n =76, 106)
Axitinib 5 mg	0.732	0.716	0.722	0.730	0.730	0.734	0.718	0.756	0.760	0.734	0.764	0.744	0.760	0.723	0.730	0.749	0.779	0.755	0.734	0.794	0.700	0.608	0.682
Sorafenib 400 mg	0.731	0.696	0.709	0.716	0.711	0.704	0.728	0.702	0.730	0.730	0.724	0.734	0.753	0.752	0.758	0.785	0.764	0.755	0.804	0.771	0.771	0.612	0.666

EQ-5D: participant rated questionnaire to assess health-related quality of life in terms of a single index value. VAS component: participants rated their current health state on a scale from 0 (worst imaginable health state) to 100 (best imaginable health state); higher scores indicate a better health. (NCT00678392)
Timeframe: Baseline (Predose on Cycle 1 Day 1) , Day 1 of each cycle until Cycle 21, End of treatment (Day 670) and Follow-up visit (Day 698)

Functional Assessment of Cancer Therapy Kidney Symptom Index-15 (FKSI-15) Score

Intervention	Units on a scale (Mean)
	Baseline (n =341, 339)	Cycle 2/Day1 (n =317, 302)	Cycle 3/Day1 (n =280, 250)	Cycle 4/Day1 (n =261, 224)	Cycle 5/Day1 (n =244, 205)	Cycle 6/Day1 (n =220, 178)	Cycle 7/Day1 (n =209, 163)	Cycle 8/Day1 (n =180, 139)	Cycle 9/Day1 (n =168, 121)	Cycle 10/Day1 (n =151, 98)	Cycle 11/Day1 (n =126, 87)	Cycle 12/Day1 (n =111, 73)	Cycle 13/Day1 (n =94, 61)	Cycle 14/Day1 (n =81, 58)	Cycle 15/Day1 (n =62, 42)	Cycle 16/Day1 (n =52, 37)	Cycle 17/Day1 (n =48, 30)	Cycle 18/Day1 (n =37, 23)	Cycle 19/Day1 (n =29, 14)	Cycle 20/Day1 (n =21, 12)	Cycle 21/Day1 (n =16, 7)	End of Treatment (n =166, 197)	Follow up (n =76, 109)
Axitinib 5 mg	70.560	69.003	69.843	69.180	69.705	69.900	69.919	70.756	70.667	70.629	72.103	71.730	70.723	69.420	73.016	70.269	71.375	70.459	71.034	73.143	74.563	61.759	64.382
Sorafenib 400 mg	70.351	67.606	69.712	70.759	71.888	71.365	72.282	71.475	73.380	75.102	74.586	73.959	75.693	75.362	75.357	73.676	73.767	73.870	70.571	66.917	64.714	61.690	66.037

FKSI was used to assess quality of life (QoL) for those diagnosed with renal cell cancer and consisted of 15 items (lack of energy, side effects, pain, losing weight, bone pain, fatigue, enjoying life, short of breath, worsened condition, appetite, coughing, bothered by fevers, ability to work, hematuria and sleep). Each of the 15 items was answered on a 5-point Likert-type scale ranging from 0 to 4 (0= not at all, 1= a little bit, 2= somewhat, 3= quite a bit, 4= very much). Total FKSI score = sum of the 15 item scores; total range: 0 - 60; 0 (no symptoms) to 60 (very much); higher scores indicate greater presence of symptoms. (NCT00678392)
Timeframe: Baseline (Predose on Cycle 1 Day 1) , Day 1 of each cycle until Cycle 21, End of treatment (Day 670) and Follow-up visit (Day 698)

Functional Assessment of Cancer Therapy Kidney Symptom Index-Disease Related Symptoms (FKSI-DRS) Score

Intervention	Units on a scale (Mean)
	Baseline (n =346, 342)	Cycle 2/Day1 (n =319, 296)	Cycle 3/Day1 (n =279, 246)	Cycle 4/Day1 (n =257, 221)	Cycle 5/Day1 (n =238, 203)	Cycle 6/Day1 (n =213, 179)	Cycle 7/Day1 (n =206, 158)	Cycle 8/Day1 (n =177, 136)	Cycle 9/Day1 (n =163, 118)	Cycle 10/Day1 (n =146, 96)	Cycle 11/Day1 (n =122, 85)	Cycle 12/Day1 (n =110, 70)	Cycle 13/Day1 (n =92, 58)	Cycle 14/Day1 (n =81, 54)	Cycle 15/Day1 (n =61, 38)	Cycle 16/Day1 (n =52, 34)	Cycle 17/Day1 (n =47, 28)	Cycle 18/Day1 (n =36, 22)	Cycle 19/Day1 (n =29, 14)	Cycle 20/Day1 (n =20, 12)	Cycle 21/Day1 (n =15, 7)	End of treatment (n=163, 191)	Follow up (n =80, 110)
Axitinib 5 mg	43.199	42.351	42.590	42.791	42.968	42.949	42.747	43.580	43.191	43.312	44.119	44.517	44.492	44.485	45.291	45.217	45.242	44.861	45.379	47.050	45.850	38.328	41.919
Sorafenib 400 mg	43.339	41.668	42.424	43.424	42.907	43.057	43.578	44.074	44.518	44.771	44.438	44.357	45.261	44.898	45.053	44.445	44.438	44.182	45.026	44.780	44.494	38.457	40.028

FKSI-DRS was used to assess quality of life for those diagnosed with renal cell cancer and consisted of 9 items (lack of energy, pain, losing weight, bone pain, fatigue, short of breath, coughing, bothered by fevers, and hematuria). Each of the 9 items was answered on a 5-point Likert-type scale ranging from 0 to 4 (0= not at all, 1= a little bit, 2= somewhat, 3= quite a bit, 4= very much). Total FKSI-DRS score = sum of the 9 item scores; total range: 0 - 36; 0 (no symptoms) to 36 (very much); higher scores indicate greater presence of symptoms. (NCT00678392)
Timeframe: Baseline (Predose on Cycle 1 Day 1) , Day 1 of each cycle until Cycle 21, End of treatment (Day 670) and Follow-up visit (Day 698)

Number of Participants With Clinically Significant Laboratory Abnormalities: Biochemistry

Intervention	Units on a scale (Mean)
	Baseline (n =346, 341)	Cycle 2/Day1 (n =319, 295)	Cycle 3/Day1 (n =279, 244)	Cycle 4/Day1 (n =257, 220)	Cycle 5/Day1 (n =238, 202)	Cycle 6/Day1 (n =213, 178)	Cycle 7/Day1 (n =206, 157)	Cycle 8/Day1 (n =177, 135)	Cycle 9/Day1 (n =163, 117)	Cycle 10/Day1 (n =146, 96)	Cycle 11/Day1 (n =122, 85)	Cycle 12/Day1 (n =110, 70)	Cycle 13/Day1 (n =92, 58)	Cycle 14/Day1 (n =81, 54)	Cycle 15/Day1 (n =61, 38)	Cycle 16/Day1 (n =52, 34)	Cycle 17/Day1 (n =47, 28)	Cycle 18/Day1 (n =36, 22)	Cycle 19/Day1 (n =29, 14)	Cycle 20/Day1 (n =20, 12)	Cycle 21/Day1 (n =15, 7)	End of Treatment (n =163, 191)	Follow up (n =80, 110)
Axitinib 5 mg	28.874	28.211	28.640	28.822	28.869	29.159	29.042	29.520	29.194	29.343	29.762	29.764	29.594	29.711	30.324	30.430	30.551	30.194	30.130	31.300	31.067	26.288	28.263
Sorafenib 400 mg	28.975	28.399	28.640	29.130	29.007	29.098	29.361	29.619	29.884	29.604	29.366	29.257	29.666	29.820	29.500	29.474	28.737	29.045	29.286	29.250	30.143	26.517	27.516

Biochemistry laboratory test included parameters: alanine aminotransferase, alkaline phosphatase, amylase, aspartate aminotransferase, bicarbonate, bilirubin, creatinine, hypercalcemia, hyperglycemia, hyperkalemia, hypernatremia, hypoalbuminemia, hypocalcemia, hypoglycemia, hypokalemia, hyponatremia, hypophosphatemia and lipase. Abnormalities were assessed by CTCAE Grade Version 2 for severity: Grade 1= mild; Grade 2= moderate; Grade 3= severe and Grade 4= life-threatening or disabling. (NCT00678392)
Timeframe: From initiation of treatment up to follow-up period (up to 3 years)

Number of Participants With Clinically Significant Laboratory Abnormalities: Hematology

Intervention	Participants (Number)
	Alanine aminotransferase: Grade 1 (n =331, 313)	Alanine aminotransferase: Grade 2 (n =331, 313)	Alanine aminotransferase: Grade 3 (n =331, 313)	Alanine aminotransferase: Grade 4 (n =331, 313)	Alkaline phosphatase: Grade 1 (n =336, 319)	Alkaline phosphatase: Grade 2 (n =336, 319)	Alkaline phosphatase: Grade 3 (n =336, 319)	Alkaline phosphatase: Grade 4 (n =336, 319)	Amylase: Grade 1 (n =338, 319)	Amylase: Grade 2 (n =338, 319)	Amylase: Grade 3 (n =338, 319)	Amylase: Grade 4 (n =338, 319)	Aspartate aminotransferase: Grade 1 (n =331, 311)	Aspartate aminotransferase: Grade 2 (n =331, 311)	Aspartate aminotransferase: Grade 3 (n =331, 311)	Aspartate aminotransferase: Grade 4 (n =331, 311)	Bicarbonate: Grade 1 (n =314, 291)	Bicarbonate: Grade 2 (n =314, 291)	Bicarbonate: Grade 3 (n =314, 291)	Bicarbonate: Grade 4 (n =314, 291)	Bilirubin: Grade 1 (n =336, 318)	Bilirubin: Grade 2 (n =336, 318)	Bilirubin: Grade 3 (n =336, 318)	Bilirubin: Grade 4 (n =336, 318)	Creatinine: Grade 1 (n =336, 318)	Creatinine: Grade 2 (n =336, 318)	Creatinine: Grade 3 (n =336, 318)	Creatinine: Grade 4 (n =336, 318)	Hypercalcemia: Grade 1 (n =336, 319)	Hypercalcemia: Grade 2 (n =336, 319)	Hypercalcemia: Grade 3 (n =336, 319)	Hypercalcemia: Grade 4 (n =336, 319)	Hyperglycemia: Grade 1 (n =336, 319)	Hyperglycemia: Grade 2 (n =336, 319)	Hyperglycemia: Grade 3 (n =336, 319)	Hyperglycemia: Grade 4 (n =336, 319)	Hyperkalemia: Grade 1 (n =333, 314)	Hyperkalemia: Grade 2 (n =333, 314)	Hyperkalemia: Grade 3 (n =333, 314)	Hyperkalemia: Grade 4 (n =333, 314)	Hypernatremia: Grade 1 (n =338, 319)	Hypernatremia: Grade 2 (n =338, 319)	Hypernatremia: Grade 3 (n =338, 319)	Hypernatremia: Grade 4 (n =338, 319)	Hypoalbuminemia: Grade 1 (n =337, 319)	Hypoalbuminemia: Grade 2 (n =337, 319)	Hypoalbuminemia: Grade 3 (n =337, 319)	Hypoalbuminemia: Grade 4 (n =337, 319)	Hypocalcemia: Grade 1 (n =336, 319)	Hypocalcemia: Grade 2 (n =336, 319)	Hypocalcemia: Grade 3 (n =336, 319)	Hypocalcemia: Grade 4 (n =336, 319)	Hypoglycemia: Grade 1 (n =336, 319)	Hypoglycemia: Grade 2 (n =336, 319)	Hypoglycemia: Grade 3 (n =336, 319)	Hypoglycemia: Grade 4 (n =336, 319)	Hypokalemia: Grade 1 (n =333, 314)	Hypokalemia: Grade 2 (n =333, 314)	Hypokalemia: Grade 3 (n =333, 314)	Hypokalemia: Grade 4 (n =333, 314)	Hyponatremia: Grade 1 (n =338, 319)	Hyponatremia: Grade 2 (n =338, 319)	Hyponatremia: Grade 3 (n =338, 319)
Axitinib 5 mg	65	8	1	0	88	8	4	0	64	12	7	0	59	5	1	0	127	11	0	1	16	8	1	0	155	30	0	0	92	8	1	0	41	45	7	0	0	42	9	0	34	19	3	0	37	11	1	0	25	4	2	1	23	12	1	0	22	0	0	0	33	0	11
Sorafenib 400 mg	57	6	2	3	92	15	3	0	76	21	6	1	67	7	4	0	115	10	0	0	12	2	1	0	121	9	1	0	22	1	0	0	28	37	7	0	0	22	8	0	23	14	1	2	25	31	2	0	67	18	2	2	9	16	1	0	21	0	5	0	27	0	6

Hematology laboratory test included hemoglobin, platelet count, white blood cells count, neutrophils and lymphocytes. Abnormalities were assessed by CTCAE Grade Version 2 for severity: Grade 1= mild; Grade 2= moderate; Grade 3= severe and Grade 4= life-threatening or disabling. (NCT00678392)
Timeframe: From initiation of treatment up to follow-up period (up to 3 years)

Number of Participants With Clinically Significant Laboratory Abnormalities: Urinalysis

Intervention	Participants (Number)
	Hemoglobin: Grade 1 (n =320, 316)	Hemoglobin: Grade 2 (n =320, 316)	Hemoglobin: Grade 3 (n =320, 316)	Hemoglobin: Grade 4 (n =320, 316)	Lymphocytes: Grade 1 (n =317, 309)	Lymphocytes: Grade 2 (n =317, 309)	Lymphocytes: Grade 3 (n =317, 309)	Lymphocytes: Grade 4 (n =317, 309)	Neutrophils: Grade 1 (n =316, 308)	Neutrophils: Grade 2 (n =316, 308)	Neutrophils: Grade 3 (n =316, 308)	Neutrophils: Grade 4 (n =316, 308)	Platelets: Grade 1 (n =312, 310)	Platelets: Grade 2 (n =312, 310)	Platelets: Grade 3 (n =312, 310)	Platelets: Grade 4 (n =312, 310)	White Blood Cells: Grade 1 (n =320, 315)	White Blood Cells: Grade 2 (n =320, 315)	White Blood Cells: Grade 3 (n =320, 315)	White Blood Cells: Grade 4 (n =320, 315)
Axitinib 5 mg	93	19	1	0	7	89	10	0	13	4	2	0	47	0	1	0	32	4	0	0
Sorafenib 400 mg	112	41	11	1	7	93	11	0	20	4	2	0	41	3	0	0	36	12	1	0

Urinalysis included urine blood/ hemoglobin, glucose and protein. Abnormalities were assessed by CTCAE Grade Version 2 for severity: Grade 1= mild; Grade 2= moderate; Grade 3= severe and Grade 4= life-threatening or disabling. (NCT00678392)
Timeframe: From initiation of treatment up to follow-up period (up to 3 years)

Percentage of Participants With Adverse Events (AEs) by Severity

Intervention	Participants (Number)
	Urine blood/ hemoglobin: Grade 1 (n =304, 272)	Urine blood/ hemoglobin: Grade 2 (n =304, 272)	Urine blood/ hemoglobin: Grade 3 (n =304, 272)	Urine blood/ hemoglobin: Grade 4 (n =304, 272)	Urine glucose: Grade 1 (n =322, 286)	Urine glucose: Grade 2 (n =322, 286)	Urine glucose: Grade 3 (n =322, 286)	Urine glucose: Grade 4 (n =322, 286)	Urine protein: Grade 1 (n =326, 289)	Urine protein: Grade 2 (n =326, 289)	Urine protein: Grade 3 (n =326, 289)	Urine protein: Grade 4 (n =326, 289)
Axitinib 5 mg	45	1	0	0	12	0	0	1	105	31	27	9
Sorafenib 400 mg	35	0	0	0	13	3	0	1	91	27	21	7

An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Severity of the AEs was graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. Grade 1= mild; Grade 2= moderate; Grade 3= severe; Grade 4= life-threatening or disabling; Grade 5= death related to AE. (NCT00678392)
Timeframe: From initiation of treatment up to follow-up period (up to 3 years)

Percentage of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)

Intervention	Percentage of participants (Number)
	Grade 1	Grade 2	Grade 3	Grade 4	Grade 5
Axitinib 5 mg	3.9	20.1	47.6	10.6	13.9
Sorafenib 400 mg	3.1	21.7	52.4	11.5	9.3

An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life- threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. A treatment emergent AE was defined as an event that emerged during the treatment period that was absent before treatment, or worsened during the treatment period relative to the pretreatment state. AEs included both serious and non-serious AEs. (NCT00678392)
Timeframe: From initiation of treatment up to follow-up period (up to 3 years)

Percentage of Participants With Treatment-Related Adverse Events (AEs) and Serious Adverse Events (SAEs)

Intervention	Percentage of participants (Number)
	AEs	SAEs
Axitinib 5 mg	96.1	40.7
Sorafenib 400 mg	98.0	35.8

An AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life -threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. AEs included both serious and non -serious AEs. (NCT00678392)
Timeframe: From initiation of treatment up to follow-up period (up to 3 years)

Article	Year
Clinicopathological spectrum of kidney diseases in cancer patients treated with vascular endothelial growth factor inhibitors: a report of 5 cases and review of literature. Human pathology, 2014, Volume: 45, Issue:9 Topics: Acute Kidney Injury; Aged; Angiogenesis Inhibitors; Antibodies, Monoclonal, Humanized; Antineoplasti	2014
Renal toxicity of targeted therapies. Targeted oncology, 2009, Volume: 4, Issue:2 Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Benzenesulfonates; Bevacizumab; Clinical	2009
[Oral drugs inhibiting the VEGF pathway]. Bulletin du cancer, 2007, Volume: 94 Spec No Topics: Administration, Oral; Angiogenesis Inhibitors; Animals; Asthenia; Axitinib; Benzenesulfonates; Human	2007
[Angiogenesis and renal cell carcinoma]. Bulletin du cancer, 2007, Volume: 94 Spec No Topics: Angiogenesis Inhibitors; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Benzenesulfonate	2007

Article	Year
Compounds targeting OSBPL7 increase ABCA1-dependent cholesterol efflux preserving kidney function in two models of kidney disease. Nature communications, 2021, 08-02, Volume: 12, Issue:1 Topics: Animals; ATP Binding Cassette Transporter 1; Biological Transport; Cells, Cultured; Cholesterol; Dia	2021
Effects of Artesunate prevent nephritis via the Toll‑like receptor 4/nuclear factor‑κB signaling pathway in rats. Molecular medicine reports, 2017, Volume: 16, Issue:5 Topics: Actins; Administration, Oral; Animals; Anti-Inflammatory Agents; Artemisinins; Artesunate; Biphenyl	2017
Expression patterns of RelA and c-mip are associated with different glomerular diseases following anti-VEGF therapy. Kidney international, 2014, Volume: 85, Issue:2 Topics: Adaptor Proteins, Signal Transducing; Adult; Aged; Angiogenesis Inhibitors; Animals; Base Sequence;	2014
1-Methylnicotinamide ameliorates lipotoxicity-induced oxidative stress and cell death in kidney proximal tubular cells. Free radical biology & medicine, 2015, Volume: 89 Topics: Albumins; Animals; Blotting, Western; Disease Models, Animal; Fatty Acids, Nonesterified; Immunohist	2015
Anti-VEGF-related thrombotic microangiopathy in a child presenting with nephrotic syndrome. Pediatric nephrology (Berlin, Germany), 2016, Volume: 31, Issue:6 Topics: Adolescent; Angiogenesis Inhibitors; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Pro	2016
Nicotinamide ameliorates a preeclampsia-like condition in mice with reduced uterine perfusion pressure. American journal of physiology. Renal physiology, 2017, Feb-01, Volume: 312, Issue:2 Topics: Animals; Blood Pressure; Embryonic Development; Female; Fetal Growth Retardation; Mice; Niacinamide;	2017
[Vascular and renal effects of anti-angiogenic therapy]. Nephrologie & therapeutique, 2008, Volume: 4, Issue:7 Topics: Angiogenesis Inhibitors; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic A	2008
Nephrotic-range proteinuria in a patient with a renal allograft treated with sorafenib for metastatic renal-cell carcinoma. Clinical and experimental nephrology, 2009, Volume: 13, Issue:4 Topics: Angiogenesis Inhibitors; Antihypertensive Agents; Benzenesulfonates; Biopsy; Carcinoma, Renal Cell;	2009
Antiangiogenic agents for the treatment of nonsmall cell lung cancer: characterizing the molecular basis for serious adverse events. Cancer investigation, 2011, Volume: 29, Issue:7 Topics: Angiogenesis Inhibitors; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Benzenesulfonate	2011
A preeclampsia-like syndrome characterized by reversible hypertension and proteinuria induced by the multitargeted kinase inhibitors sunitinib and sorafenib. Journal of the National Cancer Institute, 2008, Feb-20, Volume: 100, Issue:4 Topics: Antineoplastic Agents; Benzenesulfonates; Humans; Hypertension; Indoles; Niacinamide; Phenylurea Com	2008
Effects of very mild versus overt diabetes on vascular haemodynamics and barrier function in rats. Diabetologia, 1989, Volume: 32, Issue:12 Topics: Animals; Blood Glucose; Blood Pressure; Diabetes Mellitus, Experimental; Eating; Glomerular Filtrati	1989

niacinamide and Proteinuria