Tomita M, Ochiai M, Shu S
… +7 more, Yamauchi Y, Shihara H, Ogata A, Fujisawa N, Yanai Y, Kamata T, Iehara N
Nihon Jinzo Gakkai Shi
· 2014 · PMID 25130034
Bevacizumab, an inhibitor of vascular endothelial growth factor, is approved for the treatment of various cancers, but the incidence of proteinuria as a side effect has been reported to be 2-64%. We report a case of rena...Bevacizumab, an inhibitor of vascular endothelial growth factor, is approved for the treatment of various cancers, but the incidence of proteinuria as a side effect has been reported to be 2-64%. We report a case of renal impairment due to thrombotic microangiopathy (TMA) accompanied with glomerular subendothelial deposition of IgA resulting from bevacizumab administration. A 57-year-old female with advanced breast cancer, to whom bevacizumab had been administered from October 2012, developed proteinuria and epithelial casts in her urine about a month later. Serum creatinine remained at 0.7-0.8 mg/dL until June 2013, but gradually increased to 1.3 mg/dL in September. She was referred to our hospital because her renal function had not improved despite termination of bevacizumab, and a renal biopsy was performed in October. At that time, the levels of proteinuria, serum creatinine and serum IgA were high at 1.3 g/g x Cr, 1.6 mg/dL and 430 mg/dL, respectively. Histological examinations showed prominent IgA deposits in the subendothelial area and glomerular infiltration of CD68 positive cells in addition to features of TMA, such as narrowed glomerular capillary lumina and double contours of the basement membranes. In consideration of her clinical history, a diagnosis of bevacizumab-induced TMA was made. Through follow-up care without readministration of bevacizumab, epithelial casts in her urine disappeared, and proteinuria decreased to 0.62 g/g x Cr in November. Serum creatinine remains high at around 1.3 mg/dL, but has not elevated further. Serum IgA gradually decreased and reached 289 mg/dL in April 2014. TMA due to bevacizumab described in several other reports was also accompanied by glomerular IgA deposition, thus a differential diagnosis of IgA nephropathy is required. TMA was recently added to a section of "significant adverse effects" in the package insert of bevacizumab. Nephrologists should be fully aware of this drug-induced nephropathy.
Nagata A, Ohara A, Wakasugi D
… +5 more, Natori C, Ito S, Taguchi K, Fukami K, Okuda S
Nihon Jinzo Gakkai Shi
· 2014 · PMID 25130033
The patient was a 48-year-old man hospitalized for jaundice and anemia after a 6-day history of diarrhea. Examination demonstrated hemolytic anemia, renal dysfunction, and thrombocytopenia. Typical hemolytic uremic syndr...The patient was a 48-year-old man hospitalized for jaundice and anemia after a 6-day history of diarrhea. Examination demonstrated hemolytic anemia, renal dysfunction, and thrombocytopenia. Typical hemolytic uremic syndrome (HUS) was suspected based on the preceding colitis; however, plasma exchange (PE) was performed because the possibility of atypical HUS (aHUS) could not be ignored, given that the patient was an adult male. After 4 days of PE, his laboratory results improved. Stool culture on admission yielded negative results for Escherichia coli serotype O157 and ADAMTS13 activity. Antinuclear antibodies were normal, and no other drugs or infections indicating HUS were detected. Four months after onset, he suffered recurrence of aHUS after colitis. As a result, aHUS was suspected and therefore, PE was performed on the day of hospitalization. We diagnosed aHUS due to a result indicating complement dysregulation on hemolytic assay testing, which detected a complement factor H abnormality. After undergoing PE and maintaining a stable condition, the interval between PEs was extended; however, on day 17 after the last PE, he suffered a recurrent aHUS attack again. He could not be weaned from PE and started showing an allergic reaction to PE treatment, thereby leading to a switch from PE to eculizumab. Since switching to eculizumab treatment, the patient has not experienced another aHUS attack and his condition remains stable.
Haruhara K, Tsuboi N, Nakao M
… +6 more, Koike K, Fukui A, Miyazaki Y, Kawamura T, Ogura M, Yokoo T
Nihon Jinzo Gakkai Shi
· 2014 · PMID 25130032
The patient was a 73-year-old Japanese female diagnosed with stage IIIc primary peritoneal cancer. After undergoing total hysterectomy and bilateral oophorectomy, she received regimens consisting of paclitaxel (PTX) and...The patient was a 73-year-old Japanese female diagnosed with stage IIIc primary peritoneal cancer. After undergoing total hysterectomy and bilateral oophorectomy, she received regimens consisting of paclitaxel (PTX) and carboplatin (CBDCA). She subsequently developed recurrence four years after the disease onset and was treated with PTX, CBDCA and the vascular endothelial growth factor (VEGF) inhibitor bevacizumab (Bev). Although clinical remission was maintained with the administration of Bev monotherapy every three weeks, proteinuria was detected six months later, and gradually increased. The findings of a renal biopsy showed diffuse wrinkling and double contouring of the glomerular tufts under light microscopy, although no immune complex deposition was observed on immunostaining. Additionally, electron microscopy showed hypertrophy of glomerular endothelial cells and widening of the subendothelial spaces. These histopathological findings were fully consistent with those of reported patients treated with VEGF inhibitors. The proteinuria attenuated following the initiation of treatment with losartan. Therefore, the administration of renoprotective therapy contributed to the patient's ability to continue the anticancer regimen with Bev in this case.
Haneda M, Utsunomiya K, Koya D
… +20 more, Babazono T, Moriya T, Makino H, Kimura K, Suzuki Y, Wada T, Ogawa S, Inaba M, Kanno Y, Shigematsu T, Masakane I, Tsuchiya K, Honda K, Ichikawa K, Shide K, Joint Committee on Diabetes Nephropathy, Japanese Diabetes Society, Japanese Society of Nephrology, Japanese Society for Dialysis Therapy, Japan Society of Metabolism and Clinical Nutrition
Nihon Jinzo Gakkai Shi
· 2014 · PMID 25130030
The Committee on Diabetic Nephropathy revised the classification of diabetic nephropathy in view of the current status of eGFR and CKD in Japan. To make revisions for the classification of diabetic nephropathy 2014, the...The Committee on Diabetic Nephropathy revised the classification of diabetic nephropathy in view of the current status of eGFR and CKD in Japan. To make revisions for the classification of diabetic nephropathy 2014, the Committee carefully evaluated the report of the Research Group on Diabetic Nephropathy, Ministry of Health, Labour, and Welfare of Japan. The major revisions made were as follows: 1. eGFR can be used for the evaluation of GFR; 2. In stage 3 (overt nephropathy), A and B were combined; 3. Stage 4 (renal failure) was defined as GFR less than 30 mL/min/1.73 m2, regardless of albuminuria; and 4. The importance of differential diagnosis was stressed in all stages.
We report a case of a 63-year-old Japanese man who developed nephrotic syndrome during long-term TS-1 therapy, and was successfully treated with prednisolone (PSL). At 59 years of age, he underwent low anterior resection...We report a case of a 63-year-old Japanese man who developed nephrotic syndrome during long-term TS-1 therapy, and was successfully treated with prednisolone (PSL). At 59 years of age, he underwent low anterior resection for rectal cancer, and resection of the lateral segment of the liver for metastasis, and cholecystectomy. He received chemotherapy with intravenous infusion of fluorouracil (5-FU) 500 mg, levofolinate calcium 350 mg, and hepatic arterial infusion of 5-FU 250 mg. After 6 cycles of 5-FU therapy, TS-1 therapy was started orally at 100 mg/day for 14 days followed by 7 days of rest. Edema appeared after 2 years. Urinary protein excretion was 6.38 g/day and hematuria was observed. His serum creatinine, total protein and albumin were 0.9 mg/dL, 4.9 g/dL and 2.6 g/dL, respectively. These data pointed to nephrotic syndrome. The renal pathology revealed segmental endocapillary proliferative lesions. Postinfectious glomerulonephritis, lupus nephritis and atypical IgA nephropathy were raised for differential diagnosis based on the pathology results. However, drug-induced nephrotic syndrome was suspected from the clinical course and laboratory findings. Discontinuation of TS-1 therapy decreased urinary protein, but increased the level of serum creatinine to 1.5 mg/dL. Seven months later, steroid therapy was started at PSL 60 mg/day. Proteinuria decreased further, and the dose of PSL was tapered and stopped 22 months later. Hypofunction of the kidney persisted with serum creatinine of 1.5 mg/dL, however, urinary protein disappeared. At the onset of nephrotic syndrome, cholestatic type liver injury was observed. During steroid therapy, liver dysfunction worsened, but almost recovered with tapering of the steroid. Another case reported in the literature with the renal pathological diagnosis of nephrotic syndrome associated with TS-1 was a case of thrombotic microangiopathy (TMA). In our case, the pathologic finding was different. Furthermore steroid therapy succeeded in achieving complete remission of the nephrotic syndrome.
Maekawa K, Shibano T, Sawaki J
… +3 more, Mae H, Hattori M, Tanizawa T
Nihon Jinzo Gakkai Shi
· 2014 · PMID 24956886
PURPOSE: Glomerular macrophage accumulation is a common feature of proliferative forms of human glomerulonephritis and kidney injury. Our present study was designed to investigate the role of macrophages in pediatric kid...PURPOSE: Glomerular macrophage accumulation is a common feature of proliferative forms of human glomerulonephritis and kidney injury. Our present study was designed to investigate the role of macrophages in pediatric kidney diseases by using CD68 staining. MATERIAL AND METHODS: Seventy-four patients (39 boys and 35 girls) with pediatric kidney disease yielding 81 specimens were investigated. A monoclonal anti-human CD68 mouse antibody (KP1) was used as a macrophage marker in this study. Paraffin-embedded renal biopsy specimens were stained for immunohistochemical analysis. The average number of macrophages per glomerulus in each patient was calculated as the total number of CD68 (+) cells within all glomeruli divided by the total number of glomeruli in a single section and the average number of observed interstitial macrophages was calculated in 3-5 high power fields. RESULTS: Glomerular macrophage accumulations were increased with crescentic proliferative glomerulonephritis, mesangial proliferative glomerulonephritis, and focal segmental glomerulosclerosis. Glomerular and interstitial macrophage accumulations were correlated with hematuria, proteinuria and renal function (eGFR). In particular, activity and chronicity index, as well as the severity of glomerular IgA, C3, and fibrinogen deposition were correlated with glomerular macrophage accumulation. CONCLUSIONS: Macrophage accumulation observed by CD68 staining was a useful marker in providing a deeper understanding of the clinicopathologic state of children with chronic kidney diseases, and was effective in the selection of treatment.
Sasaki K, Yamaguchi S, Iwahashi E
… +5 more, Fujimoto T, Minami S, Rakugi H, Isaka Y, Yokoyama K
Nihon Jinzo Gakkai Shi
· 2014 · PMID 24956885
PURPOSE: Previous studies have demonstrated that almost half the deaths caused by infection in hemodialysis patients are due to pneumonia. Causative organisms in pneumonia are not defined. We assessed the positive rate o...PURPOSE: Previous studies have demonstrated that almost half the deaths caused by infection in hemodialysis patients are due to pneumonia. Causative organisms in pneumonia are not defined. We assessed the positive rate of blood and sputum cultures in a cohort of dialysis patients admitted with pneumonia. METHODS: We retrospectively enrolled 44 consecutive pneumonia patients on maintenance hemodialysis attending on outpatient clinic at a single department of nephrology between October 2005 and March 2013. Pneumonia was defined by the chest computed tomography findings and clinical status. The severity of pneumonia was scored using the pneumonia severity index (PSI) and the presumed causative organisms were identified. RESULTS: Among the 44 subjects, median age was 74 (interquartile range, 68-78) years, 90.9% were men, 28.4% had chronic obstructive pulmonary disease, and 61.4% had diabetes mellitus. Almost all patients (95.5%) were class IV or V on PSI. Blood cultures were all negative, but 36.4% of sputum cultures were positive for causative organisms. The most common pathogens were Staphylococcus aureus (13.6%), Pseudomonas aeruginosa (6.8%), Escherichia coli (4.5%), and Chlamydophila pneumonia (4.5%). The detection rate of causative organisms was related to the quality of the sputum (Group 4 and 5 of the Geckler classification) and was 61.5% in samples collected before dialysis on a day of dialysis, and 36.8% in samples collected on the day before a day of dialysis. In contrast, the detection rate was low (16.7%) when the samples were collected after dialysis on a day of dialysis. CONCLUSION: In hemodialyis patients, the detection rate of causative organisms is elevated if sputum samples are collected before undergoing dialysis on a day of dialysis. Prospective confirmation in a larger number of patients is warranted.
A 57-year old male patient was admitted to our hospital because of severe vomiting and abdominal pain with massive ascites. He had been diagnosed as mixed connective tissue disease in 1997 and lupus nephritis ISN III (A/...A 57-year old male patient was admitted to our hospital because of severe vomiting and abdominal pain with massive ascites. He had been diagnosed as mixed connective tissue disease in 1997 and lupus nephritis ISN III (A/C) + V in 2003. Treatment was started with intravenous steroid pulse therapy combined with an immunosuppressant resulting in improvement of his proteinuria and serological activity. In 2008, the disease activity flared and he was admitted to our hospital with nephrotic syndrome. Hemodialysis was unavoidable, despite treatment with intravenous steroid pulse therapy and plasma exchange. We continued to treat him with oral prednisolone and tacrolimus. However, for personal reasons, he terminated tacrolimus treatment and massive ascites remained because of insufficient hemodialysis. Since the end of 2011, he suffered repeated abdominal pain with ileus and encapsulating peritoneal sclerosis (EPS) was detected. In February 2013, he underwent synechotomy for EPS. Here, we present a rare case of EPS in a hemodialysis patient.