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*Only for medical professionals to read for reference, please pay attention! Kidney damage is a common complication of systemic lupus erythematosus (SLE), and lupus nephritis may require immunosuppressive agents to induce remission.
Intravenous cyclophosphamide has always been the main therapeutic drug for the treatment of lupus nephritis (especially type III or IV) in the active phase.
Let’s take a look at the following case published by Wong KW in BMJ Case Rep magazine [1].
Case story This is a 52-year-old woman who was admitted to the hospital for epileptic seizures 3 years ago.
Laboratory tests at the time revealed that serum albumin was 31 g/L, serum creatinine was 89 μmol/L, urine protein was 2.
23 g/d, ANA and anti- dsDNA antibody is positive, with hypocomplementemia.
The subsequent patient was diagnosed with SLE.
One month later, the patient was hospitalized again due to basal ganglia infarction.
A needle biopsy of the lower pole of the left kidney revealed lupus nephritis (Type III and Type IV by the International Society of Nephrology/Nephrology).
The activity index is 8/24, and the chronic index is 0/12.
Subsequently, the patient received an induction therapy program of intravenous injection of cyclophosphamide (once a month, 1 g each time).
After a total of 6 treatments (cumulative dose 6 g), the patient's condition reached clinical remission: recheck blood creatinine 99 μmol/L, serum Albumin was 45 g/L and proteinuria was 0.
21 g/d.
The maintenance treatment regimen is oral mycophenolate mofetil (MMF) 750 mg/time, twice a day.
Other therapeutic drugs include low-dose prednisone (5 mg/time, once a day), hydroxychloroquine (200 mg/time, once a day), and perindopril (8 mg/time, once a day) , Felodipine (10 mg/time, once a day), aspirin (75 mg/time, once a day), ranitidine (150 mg/time, once a day), potassium chloride tablets ( 600 mg/time, once a day), calcium carbonate (500 mg/time, 2 times a day).
During the regular follow-up, the patient recovered well, with normal erythrocyte sedimentation rate, renal function and serum albumin.
However, despite the disappearance of proteinuria, the patient still has persistent microscopic hematuria.
The patient's ultrasound examination revealed an exogenous mass in the left kidney.
The CT examination of the abdomen further showed that the left kidney mass was located in the upper middle pole, with a size of 5.
6 cm×5.
0 cm×6.
4 cm.
The renal cortex, parenchymal and excretory phases showed that the mass was homogeneous and enhanced with central low-density area, and the surrounding area was obvious.
The enhancement is considered to be a malignant tumor of the left kidney with metastasis to the para-aortic lymph nodes.
The doctor stopped mycophenolate mofetil and referred the patient to the urology department.
Histopathology after laparoscopic nephrectomy was confirmed to be left renal cell carcinoma.
Six months after nephrectomy, the patient was in stable condition and showed no signs of lupus activity (negative urine protein, normal erythrocyte sedimentation rate).
The doctor re-examined the original kidney biopsy section, and there was no evidence to support renal cell carcinoma.
Lupus nephritis and persistent microscopic hematuria and proteinuria and microscopic hematuria are common manifestations of patients with lupus nephritis.
For patients with type III and type IV lupus nephritis, most patients rarely have proteinuria when the induction therapy reaches remission.
However, in patients with lupus nephritis, even after complete clinical remission (no proteinuria or microalbuminuria, normal renal function, normal erythrocyte sedimentation rate and complement levels), persistent microscopic hematuria is still a very common manifestation.
Low-activity lupus nephritis after induction therapy may be a reasonable explanation for persistent microscopic hematuria, but hematuria does not always reflect the signs of active lupus nephritis [2].
However, it is worth noting that in the clinical differential diagnosis of persistent microscopic hematuria, other possibilities besides chronic kidney damage caused by lupus nephritis or SLE should be considered.
For example, in the above case, renal cell carcinoma is hidden behind lupus nephritis.
Compared with the general population, SLE patients may have a slightly increased risk of cancer, mainly hematological malignancies (especially non-Hodgkin's lymphoma).
But the potential relationship between the two is still not fully established, and the culprit of cancer may be drugs.
So far, there is no report of renal cell carcinoma associated with lupus nephritis.
Cyclophosphamide and malignant tumors Cyclophosphamide is related to the occurrence of solid tumors and hematological malignancies.
In a cohort study involving refractory rheumatoid arthritis, the incidence of malignant tumors in the cyclophosphamide treatment group was significantly higher than that in the control group, and the risk of cancer in the former was increased by 50%, among which bladder cancer and skin cancer were the Lord.
In patients with cancer (especially bladder cancer), the cumulative dose of cyclophosphamide is higher, which suggests that the carcinogenic risk of cyclophosphamide may be dose-dependent.
This carcinogenic risk (especially the risk of bladder cancer) still exists 17 years after stopping the drug [3].
Renal cell carcinoma related to cyclophosphamide is mainly seen in transplant recipients.
Patients with renal cell carcinoma after the use of cyclophosphamide may also have Wegener's granulomatosis.
Scholars such as Deger SM have reported a case of renal cell carcinoma 8 years after the onset of Wegener's granulomatosis [4].
In the above case, renal cell carcinoma occurred within 12 months after stopping cyclophosphamide.
Another possibility in this case is that the patient already had renal cell carcinoma during the active stage of lupus nephritis, but the latter was not detected by ultrasound, and subsequent cyclophosphamide treatment may accelerate the growth of the cancer.
Mycophenolate mofetil and malignant tumor mycophenolate mofetil have been widely used in patients after transplantation.
In a prospective cohort study of 6751 patients (receiving mycophenolate mofetil treatment) after primary kidney transplantation, during a 3-year follow-up period, no risk of mycophenolate mofetil and lymphoma or other malignancies after renal transplantation was found Increase the correlation [5].
Not only that, mycophenolate mofetil may also reduce the risk of malignant tumors after transplantation [5-6].
In summary, for patients with lupus nephritis who have achieved clinical remission, although persistent microscopic hematuria is usually a benign process, one should be alert to the possibility of malignant tumors.
As a drug widely used in the treatment of active lupus nephritis, when cyclophosphamide reaches a higher cumulative dose after long-term use, you should also be alert to the occurrence of malignant tumors.
Reference: [1] Wong KW.
Renal cell carcinoma with proliferative lupus nephritis.
BMJ Case Rep.
2015 Jan 16;2015:bcr2014208060.
doi:10.
1136/bcr-2014-208060.
PMID:25596289;PMCID:PMC4307063.
[2] Mittal BV,Pendse S,Rennke HG,et al.
Hematuria in a patient with class IV lupus nephritis.
Kidney Int 2006;70:1182-6.
[3]Radis CD,Kahl LE,Baker GL,Wasko MC,Cash JM, Gallatin A, Stolzer BL, Agarwal AK, Medsger TA Jr, Kwoh CK.
Effects of cyclophosphamide on the development of malignancy and on long-term survival of patients with rheumatoid arthritis.
A 20-year followup study.
Arthritis Rheum.
1995 Aug;38 (8):1120-7.
doi:10.
1002/art.
1780380815.
PMID:7639809.
[4]Deger SM,Mutluay R,Ebinc FA,Arinsoy T,Sindel S.
Renal cell carcinoma associated immunosuppressive therapy:a case report with Wegener's granulomatosis.
Rheumatol Int.
2009 Nov;30(1):119-21.
doi:10.
1007/s00296-009-0911-x.
PMID:19352681.
[5]Robson R,Cecka JM,Opelz G,Budde M,Sacks S.
Prospective registry-based observational cohort study of the long-term risk of malignancies in renal transplant patients treated with mycophenolate mofetil.
Am J Transplant.
2005 Dec;5 (12):2954-60.
doi:10.
1111/j.
1600-6143.
2005.
01125.
x.
PMID:16303010.
[6]O'Neill JO,Edwards LB,Taylor DO.
Mycophenolate mofetil and risk of developing malignancy after orthotopic heart transplantation: analysis of the transplant registry of the International Society for Heart and Lung Transplantation.
J Heart Lung Transplant.
2006 Oct;25(10):1186-91.
doi:10.
1016/j.
healun.
2006.
06.
010.
Epub 2006 Sep 18 .
PMID:17045930.
5(12):2954-60.
doi:10.
1111/j.
1600-6143.
2005.
01125.
x.
PMID:16303010.
[6]O'Neill JO,Edwards LB,Taylor DO.
Mycophenolate mofetil and risk of developing malignancy after orthotopic heart transplantation: analysis of the transplant registry of the International Society for Heart and Lung Transplantation.
J Heart Lung Transplant.
2006 Oct;25(10):1186-91.
doi:10.
1016/j.
healun.
2006.
06.
010.
Epub 2006 Sep 18.
PMID: 17045930.
5(12):2954-60.
doi:10.
1111/j.
1600-6143.
2005.
01125.
x.
PMID:16303010.
[6]O'Neill JO,Edwards LB,Taylor DO.
Mycophenolate mofetil and risk of developing malignancy after orthotopic heart transplantation: analysis of the transplant registry of the International Society for Heart and Lung Transplantation.
J Heart Lung Transplant.
2006 Oct;25(10):1186-91.
doi:10.
1016/j.
healun.
2006.
06.
010.
Epub 2006 Sep 18.
PMID: 17045930.
Intravenous cyclophosphamide has always been the main therapeutic drug for the treatment of lupus nephritis (especially type III or IV) in the active phase.
Let’s take a look at the following case published by Wong KW in BMJ Case Rep magazine [1].
Case story This is a 52-year-old woman who was admitted to the hospital for epileptic seizures 3 years ago.
Laboratory tests at the time revealed that serum albumin was 31 g/L, serum creatinine was 89 μmol/L, urine protein was 2.
23 g/d, ANA and anti- dsDNA antibody is positive, with hypocomplementemia.
The subsequent patient was diagnosed with SLE.
One month later, the patient was hospitalized again due to basal ganglia infarction.
A needle biopsy of the lower pole of the left kidney revealed lupus nephritis (Type III and Type IV by the International Society of Nephrology/Nephrology).
The activity index is 8/24, and the chronic index is 0/12.
Subsequently, the patient received an induction therapy program of intravenous injection of cyclophosphamide (once a month, 1 g each time).
After a total of 6 treatments (cumulative dose 6 g), the patient's condition reached clinical remission: recheck blood creatinine 99 μmol/L, serum Albumin was 45 g/L and proteinuria was 0.
21 g/d.
The maintenance treatment regimen is oral mycophenolate mofetil (MMF) 750 mg/time, twice a day.
Other therapeutic drugs include low-dose prednisone (5 mg/time, once a day), hydroxychloroquine (200 mg/time, once a day), and perindopril (8 mg/time, once a day) , Felodipine (10 mg/time, once a day), aspirin (75 mg/time, once a day), ranitidine (150 mg/time, once a day), potassium chloride tablets ( 600 mg/time, once a day), calcium carbonate (500 mg/time, 2 times a day).
During the regular follow-up, the patient recovered well, with normal erythrocyte sedimentation rate, renal function and serum albumin.
However, despite the disappearance of proteinuria, the patient still has persistent microscopic hematuria.
The patient's ultrasound examination revealed an exogenous mass in the left kidney.
The CT examination of the abdomen further showed that the left kidney mass was located in the upper middle pole, with a size of 5.
6 cm×5.
0 cm×6.
4 cm.
The renal cortex, parenchymal and excretory phases showed that the mass was homogeneous and enhanced with central low-density area, and the surrounding area was obvious.
The enhancement is considered to be a malignant tumor of the left kidney with metastasis to the para-aortic lymph nodes.
The doctor stopped mycophenolate mofetil and referred the patient to the urology department.
Histopathology after laparoscopic nephrectomy was confirmed to be left renal cell carcinoma.
Six months after nephrectomy, the patient was in stable condition and showed no signs of lupus activity (negative urine protein, normal erythrocyte sedimentation rate).
The doctor re-examined the original kidney biopsy section, and there was no evidence to support renal cell carcinoma.
Lupus nephritis and persistent microscopic hematuria and proteinuria and microscopic hematuria are common manifestations of patients with lupus nephritis.
For patients with type III and type IV lupus nephritis, most patients rarely have proteinuria when the induction therapy reaches remission.
However, in patients with lupus nephritis, even after complete clinical remission (no proteinuria or microalbuminuria, normal renal function, normal erythrocyte sedimentation rate and complement levels), persistent microscopic hematuria is still a very common manifestation.
Low-activity lupus nephritis after induction therapy may be a reasonable explanation for persistent microscopic hematuria, but hematuria does not always reflect the signs of active lupus nephritis [2].
However, it is worth noting that in the clinical differential diagnosis of persistent microscopic hematuria, other possibilities besides chronic kidney damage caused by lupus nephritis or SLE should be considered.
For example, in the above case, renal cell carcinoma is hidden behind lupus nephritis.
Compared with the general population, SLE patients may have a slightly increased risk of cancer, mainly hematological malignancies (especially non-Hodgkin's lymphoma).
But the potential relationship between the two is still not fully established, and the culprit of cancer may be drugs.
So far, there is no report of renal cell carcinoma associated with lupus nephritis.
Cyclophosphamide and malignant tumors Cyclophosphamide is related to the occurrence of solid tumors and hematological malignancies.
In a cohort study involving refractory rheumatoid arthritis, the incidence of malignant tumors in the cyclophosphamide treatment group was significantly higher than that in the control group, and the risk of cancer in the former was increased by 50%, among which bladder cancer and skin cancer were the Lord.
In patients with cancer (especially bladder cancer), the cumulative dose of cyclophosphamide is higher, which suggests that the carcinogenic risk of cyclophosphamide may be dose-dependent.
This carcinogenic risk (especially the risk of bladder cancer) still exists 17 years after stopping the drug [3].
Renal cell carcinoma related to cyclophosphamide is mainly seen in transplant recipients.
Patients with renal cell carcinoma after the use of cyclophosphamide may also have Wegener's granulomatosis.
Scholars such as Deger SM have reported a case of renal cell carcinoma 8 years after the onset of Wegener's granulomatosis [4].
In the above case, renal cell carcinoma occurred within 12 months after stopping cyclophosphamide.
Another possibility in this case is that the patient already had renal cell carcinoma during the active stage of lupus nephritis, but the latter was not detected by ultrasound, and subsequent cyclophosphamide treatment may accelerate the growth of the cancer.
Mycophenolate mofetil and malignant tumor mycophenolate mofetil have been widely used in patients after transplantation.
In a prospective cohort study of 6751 patients (receiving mycophenolate mofetil treatment) after primary kidney transplantation, during a 3-year follow-up period, no risk of mycophenolate mofetil and lymphoma or other malignancies after renal transplantation was found Increase the correlation [5].
Not only that, mycophenolate mofetil may also reduce the risk of malignant tumors after transplantation [5-6].
In summary, for patients with lupus nephritis who have achieved clinical remission, although persistent microscopic hematuria is usually a benign process, one should be alert to the possibility of malignant tumors.
As a drug widely used in the treatment of active lupus nephritis, when cyclophosphamide reaches a higher cumulative dose after long-term use, you should also be alert to the occurrence of malignant tumors.
Reference: [1] Wong KW.
Renal cell carcinoma with proliferative lupus nephritis.
BMJ Case Rep.
2015 Jan 16;2015:bcr2014208060.
doi:10.
1136/bcr-2014-208060.
PMID:25596289;PMCID:PMC4307063.
[2] Mittal BV,Pendse S,Rennke HG,et al.
Hematuria in a patient with class IV lupus nephritis.
Kidney Int 2006;70:1182-6.
[3]Radis CD,Kahl LE,Baker GL,Wasko MC,Cash JM, Gallatin A, Stolzer BL, Agarwal AK, Medsger TA Jr, Kwoh CK.
Effects of cyclophosphamide on the development of malignancy and on long-term survival of patients with rheumatoid arthritis.
A 20-year followup study.
Arthritis Rheum.
1995 Aug;38 (8):1120-7.
doi:10.
1002/art.
1780380815.
PMID:7639809.
[4]Deger SM,Mutluay R,Ebinc FA,Arinsoy T,Sindel S.
Renal cell carcinoma associated immunosuppressive therapy:a case report with Wegener's granulomatosis.
Rheumatol Int.
2009 Nov;30(1):119-21.
doi:10.
1007/s00296-009-0911-x.
PMID:19352681.
[5]Robson R,Cecka JM,Opelz G,Budde M,Sacks S.
Prospective registry-based observational cohort study of the long-term risk of malignancies in renal transplant patients treated with mycophenolate mofetil.
Am J Transplant.
2005 Dec;5 (12):2954-60.
doi:10.
1111/j.
1600-6143.
2005.
01125.
x.
PMID:16303010.
[6]O'Neill JO,Edwards LB,Taylor DO.
Mycophenolate mofetil and risk of developing malignancy after orthotopic heart transplantation: analysis of the transplant registry of the International Society for Heart and Lung Transplantation.
J Heart Lung Transplant.
2006 Oct;25(10):1186-91.
doi:10.
1016/j.
healun.
2006.
06.
010.
Epub 2006 Sep 18 .
PMID:17045930.
5(12):2954-60.
doi:10.
1111/j.
1600-6143.
2005.
01125.
x.
PMID:16303010.
[6]O'Neill JO,Edwards LB,Taylor DO.
Mycophenolate mofetil and risk of developing malignancy after orthotopic heart transplantation: analysis of the transplant registry of the International Society for Heart and Lung Transplantation.
J Heart Lung Transplant.
2006 Oct;25(10):1186-91.
doi:10.
1016/j.
healun.
2006.
06.
010.
Epub 2006 Sep 18.
PMID: 17045930.
5(12):2954-60.
doi:10.
1111/j.
1600-6143.
2005.
01125.
x.
PMID:16303010.
[6]O'Neill JO,Edwards LB,Taylor DO.
Mycophenolate mofetil and risk of developing malignancy after orthotopic heart transplantation: analysis of the transplant registry of the International Society for Heart and Lung Transplantation.
J Heart Lung Transplant.
2006 Oct;25(10):1186-91.
doi:10.
1016/j.
healun.
2006.
06.
010.
Epub 2006 Sep 18.
PMID: 17045930.
