Role of Dysregulated Ion Channels in Sensory Neurons in Chronic Kidney Disease-Associated Pruritus.

Background: We investigated ion channels at the skin, including peripheral nerve endings, which serve as output machines and molecular integrators of many pruritic inputs mainly received by multiple G protein-coupled receptors (GPCRs). Methods: Based on the level of chronic kidney disease-associated pruritus (CKD-aP), subjects were divided into two groups: non-CKD-aP (no or slight pruritus; n = 12) and CKD-aP (mild, moderate, or severe pruritus; n = 11). Skin samples were obtained from the forearm or elbow during operations on arteriovenous fistulas. We measured ion channels expressed at the skin, including peripheral nerve endings by RT-PCR: Nav1.8, Kv1.4, Cav2.2, Cav3.2, BKCa, Anoctamin1, TRPV1, TRPA1, and ASIC. Results: Expression of Cav3.2, BKCa, and anoctamin1 was significantly elevated in patients with CKD-aP. On the other hand, expression of TRPV1 was significantly reduced in these patients. We observed no significant difference in the levels of Cav2.2 or ASIC between subjects with and without CKD-aP. TRPA1, Nav1.8, and Kv1.4 were not expressed. Conclusions: It was concluded that this greater difference in the expression of ion channels in the skin tissue including, specially cutaneous peripheral nerve endings in CKD patients with CKD-aP may increase generator potential related to itching.

Total Calcium and Albumin Are Decreased in the Deeper Epidermis of Patients with Chronic Kidney Disease-Associated Pruritus.

BACKGROUND/AIMS: In our earlier studies, we reported high concentrations of intra- and extracellular calcium ions (Ca2+) in the deeper epidermis of patients with chronic kidney disease (CKD) and associated pruritus. To determine the cause of this phenomenon, we measured total calcium (TCa) concentrations in the deeper epidermis and performed immunostaining of epidermal albumin, which binds to Ca2+. METHODS: This study included 45 patients with CKD-stage 5, which was defined as severely reduced kidney function (i.e., estimated glomerular filtration rate less than 15 mL/min or on dialysis). Subjects were divided into the pruritus group, consisting of patients with mild, moderate, or severe uremic pruritus, and the non-pruritus group, consisting of patients with no or slight pruritus. The particle-induced X-ray emission method was used to measure elements including TCa. Furthermore, we have immunostained epidermal albumin using anti-albumin antibodies and compared the results in the pruritus and non-pruritus groups. RESULTS: The TCa concentration in the spinous layer of patients with CKD with CKD-associated pruritus was lower than in patients with CKD without pruritus (median [range], 395 [235-1,063] vs. 476 [342-1,243] µg/g). The intensity of epidermal albumin expression in the spinous layer was weaker in patients with CKD with CKD-associated pruritus than in those without. CONCLUSION: Patients with CKD with CKD-associated pruritus demonstrated higher Ca2+ concentrations but lower TCa concentrations than patients without CKD-associated pruritus. This could be in part due to low concentrations of epidermal albumin, which binds to Ca2+, in those with CKD-associated pruritus. These results clarify the pathophysiology of CKD-associated pruritus, providing a valuable foundation for the future development of treatments for this condition.

A case of fibrillary glomerulonephritis associated with thrombotic microangiopathy and anti-glomerular basement membrane antibody.

We present the first report of a case of fibrillary glomerulonephritis (FGN) associated with thrombotic microangiopathy (TMA) and anti-glomerular basement membrane antibody (anti-GBM antibody). A 54-year-old man was admitted to our hospital for high fever and anuria. On the first hospital day, we initiated hemodialysis for renal dysfunction. Laboratory data revealed normocytic-normochromic anemia with schistocytes in the peripheral smear, thrombocytopenia, increased serum lactate dehydrogenase, decreased serum haptoglobin, and negative results for both direct and indirect Coombs tests. Based on these results, we diagnosed TMA. Assays conducted several days later indicated a disintegrin-like and metalloprotease with a thrombospondin motif 13 (ADAMTS13) activity of 31.6%, and ADAMTS13 inhibitors were negative. We started plasma exchange using fresh frozen plasma and steroid pulse therapy. Anti-GBM antibody was found to be positive. Renal biopsy showed FGN. Blood pressure rose on the 46th hospital day, and mild convulsions developed. Based on magnetic resonance imaging of the head, the patient was diagnosed with reversible posterior leukoencephalopathy syndrome. Hypertension persisted despite administration of multiple antihypertensive agents, and the patient experienced a sudden generalized seizure. Computed tomography of the head showed multiple cerebral hemorrhages. However, his blood pressure subsequently decreased and the platelet count increased. TMA remitted following 36 plasma exchange sessions, but renal function was not restored, and maintenance hemodialysis was continued. The patient was discharged on the 119th day of hospitalization. In conclusion, it was shown that TMA, FGN and anti-GBM antibody were closely related.

[Correlation between re-biopsy one year after endocrine therapy and long-term prognosis in localized prostate cancer].

PURPOSE: Even in the cases of localized prostate cancer, there are a substantial number of patients who undergo endocrine therapy, and their prognosis is affected by the treatment. We evaluated the histological effect of endocrine therapy and analyzed its correlation with prognosis. METHODS AND SUBJECTS: Seventy-seven cases with localized prostate cancer who underwent maximal androgen blockade (MAB) therapy 1 year or longer were pathologically evaluated using repeat biopsy specimens from November 1994 to October 2001. The relationship between clinical parameters and histological effect in repeat biopsy specimens was examined. Biopsy was conducted mainly by the 6-site systematic method, and the histological effect was judged in accordance with the General Rules for Clinical and Pathological Study of Prostate Cancer (3rd edition). The median re-biopsy and follow-up periods were 13 months and 41 months, respectively. RESULTS: Using this criteria for the histological effects of anti-cancer treatment, the histological effect of endocrine therapy was most frequently observed in class G3b with 61.0%, and correlations with PSA nadir and initial biopsy positive number before endocrine therapy were observed. After biopsy, radical prostatectomy was performed on 9 patients (endocrine therapy was concurrently performed on 4), endocrine therapy on 67 (intermittent administration on 21), and radiation therapy on 1 (MAB was concurrently performed). Outcomes included PSA failure in 14, of whom 2 died of cancer. Three-year and 5-year PSA-failure free survival rates were 91.1% and 76.3%, respectively. Pathological disease stage in radical prostatectomy specimens was examined by dividing it into class G0-2 and class G0-3. This revealed a significant correlation between histological effect and pathological disease stage (pT2-3). PSA-failure free survival was analyzed in 67 of the 77 patients who underwent endocrine therapy. A significantly large number of PSA-failures occurred in class G0-2. Multivariate analysis revealed that the histological effect alone was the influencing factor in PSA-failure. CONCLUSION: A strong histological effect by MAB 1 year or longer after treatment was observed on localized prostate cancer. Evaluation of the histological effect by the present method was considered to be a useful predictor for organ-confined disease after radical prostatectomy and endocrine therapy for PSA-failure.

[Phyllodes tumor of the prostate: a case report].

Prostatic phyllodes tumor is an unusual lesion for which there are only occasional reports in the literature. We encountered a phyllodes tumor of the prostate in a 36-year-old man who had complained of urinary frequency and dysuria for one month. In October 1998, he visited our hospital and had a transurethral resection of the prostate (TUR-P) for obstructive symptoms. He experienced recurrent same symptoms in September 1999 and underwent another TUR-P. The pathologic examination at this time revealed phyllodes tumor. In the tumor, despite its regular alternating growth of ducts and stroma, the stromal element appeared histologically malignant, showing marked atypia and rhabdomyosarcoma-like components. Consequently, in December 1999, the patient underwent radical prostatectomy with lymph node dissection. The resection margins and pelvic lymph nodes were free of tumor. The patient remains alive and well after 14 months.