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.

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.

Successful entecavir plus prednisolone treatment for hepatitis B virus-associated membranoproliferative glomerulonephritis: A case report.

RATIONALE: Adult-onset hepatitis B virus-associated membranoproliferative glomerulonephritis (HBV-MPGN) is generally refractory, and an effective treatment for this condition has not been established. The indications for steroids in HBV-MPGN are an important clinical concern. PATIENT CONCERNS: A 28-year-old woman with a chronic hepatitis B virus infection developed nephrotic syndrome in her second month of pregnancy, with urinary protein levels of 3 to 10 g/d that continued into her postpartum period. She was a carrier of HBV with HBeAg seroconversion. As her renal impairment could have been a result of pregnancy, we observed her for 10 months postpartum without any intervention. However, spontaneous remission after childbirth was not achieved and urine protein levels were sustained at 1 to 3 g/d. About 10 months after delivery, elevated serum liver enzyme levels were observed. DIAGNOSIS: Biopsies showed MPGN, with deposition of hepatitis B antigen in the glomeruli, and chronic B-type hepatitis with a severity grade of A1F0. She was diagnosed with HBV-MPGN. INTERVENTIONS: The patient was started on entecavir 0.5 mg/d in March 2008. Within 1 month, serum HBV DNA became undetectable; within 3 months, her alanine aminotransferase levels normalized. However, urinary protein excretion did not decrease to <2 g/d. On a second renal biopsy, performed 7 months after entecavir treatment, proliferative lesions of the glomeruli were observed; therefore, prednisolone was started at an initial dose of 30 mg/d. OUTCOMES: Her proteinuria improved immediately and prednisolone was tapered over 10 months. A third renal biopsy showed a remarkable resolution of HBV-MPGN, with a significant decrease in mesangial proliferation and immune complex deposition. HBV reactivation was not observed during the prednisolone treatment. LESSONS: Additional prednisolone therapy in combination with antiviral therapy should be considered for refractory HBV-MPGN, with sufficient care taken regarding HBV reactivation.

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.

Serum Thiamine Values in End-Stage Renal Disease Patients under Maintenance Hemodialysis.

OBJECTIVE: Hemodialysis patients are prone to malnutrition because of diet or many uremic complications. The objective of this study is to determine whether thiamine deficiency is associated with regular dialysis patients. METHODS: To determine whether thiamine deficiency is associated with regular dialysis patients, we measured thiamine in 100 patients undergoing consecutive dialysis. RESULTS: Average thiamine levels were not low in both pre-hemodialysis (50.1 ± 75.9 ng/mL; normal range 24 - 66 ng/mL) and post-hemodialysis (56.4 ± 61.7 ng/mL). In 18 patients, post-hemodialysis levels of thiamine were lower than pre-hemodialysis levels. We divided the patients into two groups, the decrease (Δthiamine/pre thiamine < 0; - 0.13 ± 0.11) group (n = 18) and the increase (Δthiamine/pre thiamine> 0; 0.32 ± 0.21)) group (n = 82). However, there was no significance between the two groups in Kt/V or type of dialyzer. Patients were dichotomized according to median serum thiamine level in pre-hemodialysis into a high-thiamine group (≥ 35.5 ng/mL) and a low-thiamine group (< 35.4 ng/mL), and clinical characteristics were compared between the two groups. The low-thiamine value group (< 35.4 ng/ml; 26.8 ± 5.3 ng/ml) exhibited lower levels of serum aspartate aminotransferase and alanine aminotransferase than the high-thiamine value group (≥ 35.4 ng/ml; 73.5 ± 102.5 ng/ml) although there was no significance in nutritional marker, Alb, geriatric nutritional risk index , protein catabolic rate and creatinine generation rate. CONCLUSION: In our regular dialysis patients, excluding a few patients, we did not recognize thiamine deficiency and no significant difference in thiamine value between pre and post hemodialysis.

Association between high-molecular-weight adiponectin and bone mineral density in hemodialysis patients.

BACKGROUND: Chronic kidney disease-mineral and bone disorder is a regular complication seen in hemodialysis patients and leads to substantial increases in the fracture rate, morbidity, and mortality. Discovered a few years ago, several clinical studies have shown a negative correlation between adiponectin and bone mineral density (BMD) independently of confounding factors. The relationship between adiponectin and bone metabolism in hemodialysis patients has not been fully described yet. We conducted this study to investigate the relationship between serum adiponectin concentration and the BMD in hemodialysis patients. METHODS: We enrolled 92 hemodialysis patients who were receiving maintenance hemodialysis therapy at Towa Hospital. A peripheral blood sample was obtained, and standard biological data and the serum high-molecular-weight (HMW) adiponectin level were measured. BMD was assessed using dual-energy X-ray absorptiometry scans. RESULTS: In male hemodialysis patients, BMD was negatively related to age (r = -0.299, P = 0.012), duration of hemodialysis therapy (r = -0.31, P = 0.009), and log [HMW-adiponectin] (r = -0.31, P = 0.009) and positively related to body weight (r = 0.332, P = 0.004) and BMI (r = 0.297, P = 0.013). In female hemodialysis patients, BMD was negatively related to age (r = -0.499, P = 0.018) and log [HMW-adiponectin] (r = -0.46, P = 0.030) and positively related to triglyceride (r = 0.491, P = 0.020). CONCLUSIONS: HMW adiponectin may affect bone metabolism in both male and female hemodialysis patients.

Effect of single-dose rituximab on steroid-dependent minimal-change nephrotic syndrome in adults.

BACKGROUND: Steroid-dependent minimal-change nephrotic syndrome (MCNS) requires administration of prolonged courses of prednisolone (PSL); therefore, a paradigm shift from such toxic 'non-specific' therapies to selective immunomodulating regimens is necessary for these cases. METHODS: To assess the therapeutic effects of rituximab (an anti-CD20 antibody) in adult patients with steroid-dependent MCNS, we performed a prospective trial of the effects of a single dose of rituximab administered twice at an interval of 6 months in 25 MCNS patients. We evaluated the biochemical parameters and compared the clinical findings between the 12-month period before and 12-month period after the first rituximab infusion. RESULTS: A significant reduction in the number of relapses and the total dose and the maintenance dose of PSL administered was observed during the 12-month period after the first rituximab infusion when compared with the findings during the 12-month period before the first rituximab infusion [25 (100%) versus 4 (16%), P < 0.001; 8.2 versus 3.3 g, P < 0.001; 26.4 mg/day at baseline versus 1.1 mg/day at 12-month, P < 0.0001]. Complete remission was achieved/maintained in all patients undergoing B-cell depletion. Four of 17 patients with B-cell repletion developed relapse. CONCLUSIONS: Our results revealed that rituximab therapy was associated with a reduction in the number of relapses and in the total dose of PSL needed. Therefore, rituximab appears to be a useful therapeutic agent for adult patients with steroid-dependent MCNS. These results suggest that this treatment is rational and should be considered as an important option in the management of adult patients with steroid-dependent MCNS.

Overweight and obesity accelerate the progression of IgA nephropathy: prognostic utility of a combination of BMI and histopathological parameters.

BACKGROUND: Although more than 40 years have passed since IgA nephropathy (IgAN) was first reported, predicting the renal outcome of individual IgAN patients remains difficult. Emerging epidemiologic evidence indicates that overweight and obesity are risk factors for end-stage renal disease. We aimed to elucidate the outcome of overweight IgAN patients and improve our ability to predict the progression of IgAN based on a combination of body mass index (BMI) and histopathological parameters, including maximal glomerular area (Max GA). METHODS: Forty-three adult IgAN patients whose estimated glomerular filtration rate was ≥50 ml/min/1.73 m(2) were enrolled in this study. Renal biopsy specimens were evaluated according to the Oxford classification of IgAN. A Kaplan-Meier analysis and the multivariate Cox proportional hazards method were used to evaluate 10-year kidney survival and the impact of covariates. The ability of factors to predict the progression of IgAN was evaluated by their diagnostic odds ratio (DOR). RESULTS: A BMI ≥25 kg/m(2) was found to be an independent predictor of a ≥1.5-fold increase in serum creatinine value (DOR 7.4). The combination of BMI ≥25 kg/m(2), Max GA ≥42,900 µm(2), and presence of mesangial hypercellularity (Oxford M1) optimally raised predictive power for disease progression of IgAN (DOR 26.0). CONCLUSION: A combination of BMI ≥25 kg/m(2), the Oxford classification M1, and a Max GA ≥42,900 µm(2) can serve as a predictor of long-term renal outcome of IgAN.

Comparison of inhibitors of renin-angiotensin-aldosterone system (RAS) and combination therapy of steroids plus RAS inhibitors for patients with advanced immunoglobulin A nephropathy and impaired renal function.

BACKGROUND: The adaptation of steroid therapy and the effect of renin-angiotensin-aldosterone system inhibitors (RASIs) for advanced immunoglobulin A nephropathy (IgAN) patients with impaired renal function are still controversial. METHODS: We divided 63 IgAN patients with an estimated glomerular filtration rate (eGFR) of <60 ml/min/1.73 m(2) and proteinuria ≥ 0.5 g/day into two groups: the RASI group (RASI, n = 33), treated with RASIs alone; and the combination group (COMBI, n = 30), treated with corticosteroids and RASIs. We analyzed the clinical and histological background, renal survival rate, and the risk factors for progression. RESULTS: Renal function (mean eGFR: COMBI 46.4 vs. RASI 47.0 ml/min/1.73 m(2)), the amount of proteinuria (median: COMBI 1.39 vs. RASI 1.17 g/g creatinine) and histological backgrounds were not significantly different between the groups, but urinary red blood cells (U-RBCs) were significantly higher in the COMBI group than in the RASI group (median: COMBI 30.0 vs. RASI 10.0 counts/high-power field, P = 0.0171). The serial change in proteinuria did not differ until 5 years after treatment, but U-RBCs were significantly decreased in both groups (P < 0.0001), and eGFR was significantly decreased in the RASI group (P < 0.001) but not in the COMBI group. The results for each year after treatment did not differ significantly between both groups. The renal survival rate was not significantly different between the groups. There was no independent risk factor for progression by Cox regression analysis. CONCLUSION: Combination therapy with steroids and RASIs was not superior to monotherapy with RASIs for advanced IgAN with impaired renal function.

Comparison of serum albumin, serum C-reactive protein, and pulse wave velocity as predictors of the 4-year mortality of chronic hemodialysis patients.

AIM: Although serum albumin and C-reactive protein (CRP) levels and pulse wave velocity (PWV) are known to be associated with the clinical outcome of hemodialysis (HD) patients, it is unknown which of these parameters are more predictive of the long-term mortality of such patients. METHODS: We measured biochemical parameters, including serum albumin and CRP, and the PWV of 202 patients on maintenance HD therapy and followed their course for 4 years, and 186 of the patients were enrolled in the current study analyses. We divided the 186 patients into three tertiles according to their serum albumin and CRP levels and PWV values, and conducted multivariate analyses to examine the impact of the tertiles on 4-year mortality. RESULTS: Twenty-three (12.4%) patients died during the follow-up period, and the serum albumin of the group that died was significantly lower than in the group that survived, but the CRP levels and PWV were significantly higher in the group that died. The results of Kaplan-Meier analyses revealed a significantly higher risk of all-cause mortality in HD patients with higher CRP based on the results of Cox proportional hazards analyses; however, the serum albumin and PWV values were not associated with all-cause mortality. CONCLUSION: The results of this study suggest that serum CRP levels are a better mortality predictor than serum albumin or PWV values of chronic HD patients.

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.

Comparison of steroids and angiotensin receptor blockers for patients with advanced IgA nephropathy and impaired renal function.

BACKGROUND/AIMS: The therapeutic strategy for advanced IgA nephropathy patients with impaired renal function is still controversial. PATIENTS AND METHODS: We divided 44 IgA nephropathy patients with an estimated glomerular filtration rate (eGFR) of less than 60 ml/min/1.76 m(2) and proteinuria greater than 0.5 g/g · creatinine into two groups: the angiotensin receptor blocker (ARB) group (n = 22), treated with ARBs, and the steroid group (n = 22), treated with corticosteroid. We analyzed the clinical and histological background, renal survival rate until progression to end-stage renal disease (ESRD), and the risk factors for progression. RESULTS: The clinical and histological backgrounds were not significantly different between the groups. At 1 and 2 years after treatment, proteinuria tended to be decreased from baseline in both groups, but not significantly, and urinary red blood cells were significantly decreased in the steroid groups (p < 0.001), but not in the ARB group. The eGFR tended to be increased in the steroid group and decreased in the ARB group. However, the renal survival rate until ESRD was not significantly different between the groups. There were no significant independent risk factors for progression. CONCLUSION: The beneficial effect of ARBs on renal survival of advanced IgA nephropathy with impaired renal function is equal to that with steroids.

Effect of single-dose rituximab on primary glomerular diseases.

BACKGROUND: A paradigm shift from such toxic 'nonspecific' therapies to selective immunomodulating regimens is necessary for glomerular diseases. Rituximab, which acts by inhibiting CD20-mediated B cell proliferation and differentiation, could be effective in the treatment of nephrotic syndrome as shown in recent reports. DESIGN: To assess the effects of rituximab in patients with primary glomerular diseases, including minimal-change disease, immunoglobulin A (IgA) nephropathy, focal segmental glomerulonephritis, membranous nephropathy and membranoproliferative glomerulonephritis, we performed a prospective trial of the effects of single-dose rituximab therapy in 24 patients. We prospectively evaluated the serum and urinary biochemical parameters before and after 6 months of therapy. RESULTS: In all of the patients studied, depletion of CD19 and CD20 cells was noted, with significant reduction in the degree of proteinuria from 3.7 ± 3.4 g/day at baseline to 1.3 ± 2.0 g/day at 6 months after the drug administration (p = 0.002). However, no significant changes of the serum creatinine, urinary RBC sediment, serum CD4/8 or serum IL-4 levels were observed at 6 months after the drug administration. In subjects with IgA nephropathy, while depletion of CD19 and CD20 cells was noted, no significant change in the severity of proteinuria was observed at 6 months after the drug administration as compared with the level at the baseline. CONCLUSION: For the treatment of primary glomerular diseases, the use of a single dose of rituximab is demonstrated with no serious adverse events. Further study of the mechanism of action of rituximab in successfully treated patients could encourage new perspectives in the treatment of primary glomerular diseases.

Risedronate therapy for the prevention of steroid-induced osteoporosis in patients with minimal-change nephrotic syndrome.

BACKGROUND: Minimal-change nephrotic syndrome (MCNS) is treated by the administration of prednisolone (PSL) at high doses. Steroid-induced osteoporosis is a serious adverse effect of this drug. METHODS: Patients with MCNS were randomly assigned to two groups, the risedronate (2.5 mg/day) + alfacalcidol (0.25 µg/day) group (n=20) and the alfacalcidol (0.25 µg/day)-alone group (n=20). All the patients had received PSL and the clinical characteristics were compared between the two groups at baseline and at 12 months. RESULTS: A significant decrease of the mean bone mineral density (BMD) of the lumbar spine from 0.710±0.162 (g/cm(2)) to 0.588±0.125 was observed in the alfacalcidol-alone group (p=0.02), while no such decrease of the bone mineral density was found in the risedronate + alfacalcidol group (0.663±0.169 at baseline and 0.626±0.129 at 12 months). No significant differences in the results of other biochemical tests performed at the baseline and at 12 months were observed between the two groups. The likelihood of development of steroid-induced osteoporosis was influenced by the cumulative dose of PSL, the mean BMD at the baseline, occurrence of disease relapse, and risedronate therapy. CONCLUSION: Risedronate appears to be effective in preventing steroid-induced osteoporosis. It is necessary to use bisphosphonates to maintain the BMD in patients with MCNS receiving prolonged steroid therapy.