Dynamics of d -serine reflected the recovery course of a patient with rapidly progressive glomerulonephritis Abstract We experienced a case of a 36-year-old female with rapidly progressive glomerulonephritis (RPGN) due to anti-neutrophil cytoplasmic antibody (ANCA)-associated nephritis and systemic lupus erythematosus (SLE) nephritis. Chiral amino acid metabolomics revealed a prominent profile of d-serine in this patient. At the fulminant period of RPGN, the level of plasma d-serine, a potential biomarker in CKD that reflects actual glomerular filtration ratio (GFR), was extremely high. On the other hand, urinary fractional excretion (FE) of d-serine, which was usually much higher than that of l-isoform, was 0% in this patient. These abnormal d-serine profiles normalized in response to the intensive treatment. Normalizations of blood d-serine levels were in parallel with those of blood creatinine levels and potentially reflect the recovery of GFR. FE of d-serine increased transiently before the normalization of d-serine profile, suggesting that kidney promotes urinary excretion of d-serine for the normalization of plasma d-serine level. These unexplored clinical features of d-serine well reflected the clinical course of this patient. Blood d-serine level can also serve as a biomarker in acute kidney injury (AKI) or RPGN, and, in combination with FE of d-serine, may render the clinical practitioners to judge the efficacy of intensive treatments.

Readers response to “Sequential nonarteritic anterior ischemic optic neuropathy in patient on chronic hemodialysis”

Hemophagocytic syndrome with acute kidney injury accompanied by erythrophagocytic macrophages in the tubular lumen Abstract Hemophagocytic syndrome (HPS) is a life-threatening syndrome involving excessive immune activation. It is often accompanied by renal involvement known as acute kidney injury (AKI), which is a poor prognostic factor of HPS. Thus, early diagnosis and treatment are very important. However, it is rarely identified in renal biopsy specimens, and its major manifestation is acute tubular necrosis. We report a rare case of erythrophagocytic macrophage presence in the tubular lumen of a patient with HPS-associated AKI. A kidney biopsy showed acute tubular necrosis, interstitial massive macrophage infiltration, and phagocytic macrophage casts without glomerular change. Some arteriolar vascular smooth muscle cells showed vacuolization because they were positive for α-smooth muscle actin. The patient’s renal function improved after methylprednisolone pulse therapy followed by oral prednisolone after a month. Our case presents a new pathologic pattern of HPS. Careful urinalysis could suggest renal involvement with HPS. Having knowledge of this pathologic pattern of HPS is important to recognize the disease and to treat it appropriately.

Arteriovenous fistula-related renal bleeding 5 days after percutaneous renal biopsy Abstract A 32-year-old Japanese woman was admitted to our hospital for evaluation of microscopic hematuria with a positive family history. Percutaneous renal biopsy was performed under real-time ultrasound guidance using a 16-gauge automated needle and three specimens were obtained. She had no risk factors for hemorrhage. However, macroscopic hematuria developed from 5 days after biopsy and persisted for 4 days. Her Hb decreased markedly from 15.0 to 8.1 g/dL. Enhanced computed tomography revealed urinary tract hematoma, while the early arterial phase showed inflow of contrast medium into the left renal vein from a pseudoaneurysm on a branch left renal artery. Renal transcatheter arterial embolization was performed using platinum microcoils and the arteriovenous fistula was occluded. The patient did not require blood transfusion. Severe renal bleeding that causes urinary tract hematoma usually occurs within 24 h after renal biopsy, but the possibility of late-onset renal bleeding should be kept in mind.

Successful treatment with voriconazole combined with amphotericin B-liposome for fluconazole-resistant pulmonary cryptococcosis after renal transplantation Abstract Cryptococcosis is an invasive fungal infection that is common among organ transplant recipients, and it is challenging to treat among these patients because of their immunocompromised status. Fluconazole (FLCZ) is recommended as a first-line treatment modality for pulmonary cryptococcosis in organ transplant recipients. However, cases of FLCZ resistance among Cryptococcus neoformans isolates have been reported from the Asia Pacific region. Previous studies have reported the efficacy of voriconazole (VRCZ) in patients with FLCZ-resistant fungal infections. Herein, we report a case of FLCZ-resistant pulmonary cryptococcosis after renal transplantation that was successfully treated with VRCZ combined with amphotericin B-liposome (L-AMB). The patient was a-23-year-old woman who underwent living-donor kidney transplantation at age 20 years. She has attended our hospital since before for mental retardation, epilepsy, and dilated cardiomyopathy. At age 23 years, she presented to our hospital with fever and cough. She was diagnosed with pulmonary cryptococcosis based on positive-serum cryptococcal antigen. Chest radiography showed bilateral consolidations. Fosfluconazole (F-FLCZ) was administered, and her condition improved. However, she developed cough and fever again on day 60 of hospitalization. Cryptococcosis recurrence was suspected due to the high degree of cryptococcal antigen titers showed (1:2048) taken on the same day. Therefore, L-AMB was added, and F-FLCZ was substituted with VRCZ. Her condition improved, but L-AMB was discontinued due to hyponatremia, hypokalemia, and elevated serum creatinine. This indicates that VRCZ caused the remission. She was discharged after 6 months of admission. In conclusion, this case shows the efficacy of VRCZ combined with L-AMB for refractory pulmonary cryptococcosis.

List of referees

Misdiagnosis of high anion gap acidosis owing to instrument error of a device Abstract The anion gap (AG) is a tool to diagnose metabolic acid–base disorders in the physiological approach to acid–base assessment. It is used to detect high AG acidosis, a type of metabolic acidosis caused by serum concentration increase in usually unmeasured anions; AG larger than the reference for it indicates the presence of high AG acidosis. This report presents a case of hyperlactatemia which was not detected as high AG acidosis possibly because of instrument error of a device in measurement of serum sodium and chloride concentrations. The case indicates that the error will make AG unable to detect high AG acidosis of any cause. Hence, upon suspicion of high AG acidosis caused by measurable anions such as lactate and ketones, it is recommended to measure their serum concentration.

Brown tumor of the thoracic spine presenting with paraplegia in a patient with peritoneal dialysis Abstract Secondary and tertiary hyperparathyroidism is an important problem of chronic kidney disease. Brown tumor is a benign, unusual, reactive lesion as a result of disturbed bone remodeling, from long-standing increase in parathyroid hormone level. Brown tumors may cause morbidity due to pressure symptoms on neural structures and spontaneous bone fractures. Herein, we presented a peritoneal dialysis patient with tertiary hyperparathyroidism under calcand calcitriol treatment for 4 years due to refusing of the parathyroidectomy operation. She admitted to hospital for sudden onset back pain with difficulty in gait and walking, and imaging studies showed an expansile mass lesion in the thoracic spine. She was operated for mass and diagnosed with brown tumor. After operation, she lost the ability of walking than become paraplegic and she underwent rehabilitation program. Preventive measures including calcitriol and cinacalcet may cause a modest decrease in parathyroid hormone levels but it should be remembered for the development of bone complications such as brown tumor formation in patients with moderate elevated PTH levels, especially those with tertiary hyperparathyroidism. Parathyroidectomy should be performed without delay in these cases.

Atypical reduction of plasma ADAMTS13 activity by a non-IgG-type inhibitor in a patient with hemolytic uremic syndrome caused by Shiga toxin-producing Escherichia coli Abstract Thrombotic microangiopathies include hemolytic uremic syndrome (HUS) and thrombotic thrombocytopenic purpura (TTP). Measurement of plasma levels of “a disintegrin-like and metalloproteinase with thrombospondin type 1 motifs 13” (ADAMTS13) activity can distinguish HUS from TTP. Reduced plasma ADAMTS13 activity (< 10% normal range) is atypical for HUS, but not for TTP. However, we detected reduced ADAMTS13 activity in a patient with Shiga toxin-producing Escherichia coli-associated HUS caused by non-IgG anti-ADMTS13 autoantibodies. Furthermore, the patient exhibited possible genetic abnormalities associated with atypical HUS. The patient fully recovered after administration of supportive therapy. To the best of our knowledge, very few cases of STEC-HUS with reduced ADAMTS13 activity have been reported; thus far, none have described the presence of non-IgG anti-ADMTS13 autoantibodies. Therefore, we suggest that anti-ADAMTS13 analyses should be performed in patients diagnosed with STEC-HUS, especially in those who present with prolonged healing or unexpected clinical symptoms.

Autosomal dominant Alport syndrome due to a COL4A4 mutation with an additional ESPN variant detected by whole-exome analysis Abstract Alport syndrome (AS) is a rare hereditary disease that presents with chronic kidney disease and sensorineural hearing loss, and is diagnosed by its clinical features, pathological features on renal tissue, and mode of inheritance. We report a woman in her 20 s who exhibited persistent haematuria with normal renal function and sensorineural hearing loss. Her family members exhibited the same clinical findings among three generations and were suspected of having autosomal dominant AS (ADAS). Renal biopsy showed minor glomerular abnormalities on light microscopy and extensive thinning of the glomerular basement membrane on electron microscopy. Whole-exome analysis revealed a known COL4A4 (type IV collagen α4) mutation (c. 2510 G > C: p. Gly837Ala). Two pedigrees with the same variant have been reported previously, one as ADAS and the other as autosomal recessive AS. However, these two cases exhibited no sensorineural hearing loss. The analysis in the present case revealed another missense variant in ESPN (Espin), an actin-bundling protein, which is a causative gene for sensorineural hearing loss. Although the pathophysiological significance of this novel missense variant needs to be clarified, computational analysis predicted that the variant creates a new phosphorylation site for protein kinase C. Our case suggests a possible association of hereditary sensorineural hearing loss with ADAS. Whole-exome analysis should be considered to diagnose hereditary and multiple-organ disorders.