Risk factors for cytomegalovirus reactivation in patients with kidney disease under immunosuppressive therapy.

BACKGROUND: Cytomegalovirus (CMV) is a herpes virus that causes latent infections, and its reactivation due to immunosuppression can cause fatal complications. CMV reactivation is a complication frequently occurring in patients with kidney disease who require immunosuppressive therapy, and, therefore, this study retrospectively examined its risk factors. METHODS: Patients who received immunosuppressive therapy and underwent the CMV antigenemia test (CMV antigenemia: C7-HRP) for the treatment of primary nephritis (minimal change disease, membranous nephropathy, membranoproliferative glomerulonephritis, focal glomerulosclerosis, and IgA nephropathy) and anti-neutrophil cytoplasmic autoantibody (ANCA)-associated nephritis diagnosed at Saiseikai Kurihashi Hospital from January 2014 to December 2019 were recruited as study participants. Risk factors of CMV reactivation were examined using univariable and multivariable analyses. RESULTS: Among the 64 patients (36 men and 28 women; median age, 72 years) included, 34 had primary nephritis (20 minimal disease changes, 10 membranous nephropathy, 1 membranoproliferative glomerulonephritis, 1 focal glomerulosclerosis, and 2 IgA nephropathy) and 30 had ANCA-associated nephritis. Regarding glucocorticoid (GC), 43 patients received oral GC therapy, whereas 21 received GC pulse therapy. CMV reactivation participants showed significant differences in age, ANCA-associated nephritis, hemoglobin level, lymphocyte count, maximum GC dosage, and hemodialysis in univariable analysis. Multivariate analysis showed significantly lower lymphocyte counts in CMV-reactivated patients, but no significant difference in other factors. CONCLUSION: In patients with kidney disease, who require immunosuppressive therapy, CMV reactivation risk is high in patients with low lymphocyte count, and monitoring CMV during the treatment course could lead to early diagnosis and treatment of CMV disease.

A case of medullary cystic kidney disease with rapid progressive renal dysfunction and kidney enlargement.

Medullary cystic kidney disease (MCKD) is usually associated with slowly progressive kidney injury. However, we encountered a case of MCKD with rapidly progressive kidney injury and irreversible renal dysfunction. A 63-year-old woman presented with a 4-month history of hypertension and rapidly progressive renal dysfunction. On admission, her blood pressure was slightly elevated (158/85 mmHg). The scrum creatinine (11.57 mg/dL) was markedly elevated. Urinalysis showed occult hematuria and proteinuria(1.06 g/gCr). /ß2- microglobulin 45,000 µg/ L, N-acetyl-/ß-D-glucosaminidase 5.6 U/L. Neither ultrasonography nor computed tomography revealed any evidence of renal medullary cysts. Both kidneys showed an irregular surface and enlargement. Microscopic evaluation of the renal biopsy revealed extensive tubular dilatation and atrophy with interstitial fibrosis. Often glomeruli, one had global sclerosis and the others were normal. The tubular dilatation was more marked in the distal than in the proximal tubules, according to the immunohistochemical findings of positivity for epithelial membrane antigen (EMA), a marker of distal tubules, and negativity for CD 10, a marker of proximal tubules. No immunoglobulin or complement deposition was detected in either the glomeruli or the tubules. Electron microscopy revealed disintegration of the tubular basement membrane with fragile thinning and lamination of the membrane. These pathological findings were compatible with MCKD. This was a case of MCKD diagnosed incidentally in an elderly patient who presented with rapidly progressive kidney injury accompanied by hypertension. Renal biopsy was necessary for the diagnosis.

S100A12 gene expression is increased in peripheral leukocytes in chronic kidney disease stage 4-5 patients with cardiovascular disease.

BACKGROUND/AIMS: S100A12 induces vascular inflammation contributing to the development of atherosclerosis. Serum S100A12 concentration is shown to be elevated in patients with chronic kidney disease (CKD), however the reason remains unclear. METHODS: Transcriptional levels of S100A12 and RAGE (receptor for advanced glycation end products) were measured in peripheral leukocytes by quantitative real-time RT-PCR. Subjects were 40 patients with CKD stage 4-5, 20 of whom were affected with cardiovascular disease (CVD), and 20 healthy subjects. Serum concentrations of S100A12 and soluble RAGE were measured using enzyme-linked immunosorbent assay. RESULTS: The serum concentration of S100A12 was significantly higher in CKD patients than in healthy subjects (78.5 ± 70.5 vs. 23.7 ± 19.2 ng/ml, p = 0.0035), but that of soluble RAGE was not. The relative quantity of S100A12 mRNA was significantly greater in leukocytes from CKD patients than in those from healthy subjects [mean (95% confidence interval of the mean): 3.1 (2.2-3.9) vs. 1.2 (0.8-1.7), p = 0.0001], however that of RAGE mRNA was not. The serum concentration of S100A12 was significantly correlated with the relative quantity of S100A12 mRNA among uremic CKD patients (r(2) = 0.656, p < 0.0001). Both the serum concentration and gene expression of S100A12 were significantly higher in patients who had CVD than in those who did not. CONCLUSION: Excessive expression of the S100A12 gene in uremic leukocytes is relevant to its increased serum concentration, particularly in those affected with CVD.

Induction of remission following a single dose of rituximab alone in a patient with minimal change nephrotic syndrome.

Treatment with a single dose of rituximab alone induced remission in a patient with relapsed minimal change nephrotic syndrome (MCNS). A 27-year-old man was given corticosteroid (prednisolone; PSL) and cyclosporine (CyA) therapy combined with rituximab for his fifth relapse in 2008. Thereafter, complete remission was achieved and maintained despite eventual discontinuation of the PSL and CyA. In 2010, we treated his sixth relapse with a single dose of rituximab. Complete remission was obtained 32 days later. This is the first report of rituximab monotherapy in the treatment of MCNS.

Late-Onset Neutropenia after Rituximab Treatment for Adult-Onset Nephrotic Syndrome.

A 41-year-old woman developed nephrotic syndrome at the age of 32 and was diagnosed with minimal change nephrotic syndrome based on a renal biopsy. Although remission was achieved with administration of prednisolone (PSL) and cyclosporine, the nephrotic syndrome recurred. She was also started on rituximab (RTX). She developed late-onset neutropenia after RTX treatment (R-LON) and improved 17 days later. Although the majority of R-LON cases undergo spontaneous remission, cases of death have been reported. This report is intended to warn about R-LON, since the use of RTX for adult-onset nephrotic syndrome is expected to increase in the future.

Association between Ophthalmological Changes and Cardiovascular Diseases in Patients with Chronic Kidney Disease Undergoing Hemodialysis.

AIMS: Patients with chronic kidney disease (CKD) undergoing hemodialysis (HD) have a high prevalence of cardiovascular diseases (CVD). Arterial sclerosis plays an important role in the pathogenesis of CVD. However, to date, there have been no reports of assessment of the association between retinal arterial sclerosis and CVD in patients with CKD on HD. The aim of this study was to assess retinal arterial sclerosis and to investigate the relationship between retinal arterial changes in patients with CKD on HD and arterial stiffness/past history of CVD. METHODS: We examined the data of 44 patients (21 female, 23 male) with CKD receiving HD treatment at Saiseikai Kurihashi Hospital. The relationship between ophthalmological changes and arterial stiffness [pulse wave velocity (PWV)] or past history of CVD was evaluated. All medications being taken were recorded, and biochemical parameters were analyzed. RESULTS: Significant correlations were found between the presence of arteriosclerotic retinopathy [Scheie classification S grade (grade 0: 7 patients, grade 1: 18 patients, grade 2: 14 patients, grade 3: 4 patients, and grade 4: 1 patient)] and results of the evaluation of arterial stiffness (PWV) and past history of CVD (p=0.001, p=0.045). Other ophthalmological findings were not associated with a history of CVD or arterial stiffness. CONCLUSION: We showed that the classification (Scheie S grade) of retinopathy on ophthalmoscopic examination may be a useful tool for predicting arterial stiffness and its association with CVD.