Factors Contributing to Erythropoietin Hyporesponsiveness in Patients on Long-Term Continuous Ambulatory Peritoneal Dialysis: A Cross-Sectional Study.

BACKGROUND: Factors contributing to erythropoietin (EPO) hyporesponsiveness in patients on long-term continuous ambulatory peritoneal dialysis are not well understood. Therefore, we investigated the factors contributing to EPO hyporesponsiveness using the EPO resistance index (ERI). METHODS: A total of 14 patients (7 males and 7 females, age 65.0 ± 11.9 years) were selected for this study. We defined ERI as the weekly dose of EPO per body weight divided by hemoglobin (U/kg/g/dl/week). Bioelectrical impedance analysis was used to assess the patients' body composition and fluid status. We examined associations between ERI and clinical parameters, such as physiological, chemical and nutrition status, by correlation and multiple linear regression analyses. RESULTS: Peritoneal dialysis duration was 95 ± 23 months, and all patients underwent peritoneal dialysis for >5 years. Hemoglobin, blood pressure and ultrafiltration volume of peritoneal dialysis were 11.5 ± 1.2 g/dl, 123 ± 14/72 ± 8 mm Hg and 834 ± 317 ml/day, respectively. Renal Kt/V and peritoneal Kt/V, which are indices of dialysis adequacy, were 0.32 ± 0.31 and 1.70 ± 0.31, respectively. Age and extracellular water/total body water (ECW/TBW) ratio had significant positive correlations with ERI (both p < 0.05). Levels of C-reactive protein, serum albumin, parathyroid hormone and normalized protein catabolic rate were not significantly correlated with ERI. In a multiple regression analysis, ECW/TBW was independently associated with ERI (p < 0.05). CONCLUSIONS: This study demonstrates that ECW/TBW was a factor contributing to ERI and that appropriate maintenance of body fluid volume could contribute to low EPO dosing.

Nephrology pre-dialysis care affects the psychological adjustment, not only blood pressure, anemia, and phosphorus control.

Several studies have suggested that pre-dialysis care is associated with clinical outcomes. However, little has been reported on the influence of pre-dialysis care on the psychological adjustment to dialysis. The purpose of this study was to evaluate the impact of pre-dialysis care on psychological adjustment to dialysis and clinical characteristics. In this cross-sectional study, we enrolled 52 patients who started hemodialysis at our hospital. They were divided into two groups according to the time of referral to our hospital: the early referral group (over 1 year prior to first dialysis: 19 patients, mean age 69.3 ± 11.1) and the late referral group (within 1 year prior to first dialysis: 33 patients, mean age 72.3 ± 8.9). We measured the clinical characteristics and evaluated the psychological adjustment to dialysis by Shontz's stage theory. Compared with the late referral group, the early referral group had a significantly better clinical characteristics concerning blood pressure (140.2 ± 23.7 vs. 156.9 ± 23.3 mmHg, P = 0.0150), hemoglobin (10.3 ± 1.5 vs. 9.4 ± 1.0 g/dL, P = 0.0078), and phosphorus (4.5 ± 1.5 vs. 5.5 ± 1.3 mg/dL, P = 0.0166). In addition, psychological adjustment to dialysis evaluated by Shontz's stage theory was significantly better in the early referral group (P = 0.017). Our results indicate that nephrology pre-dialysis care affects not only blood pressure, anemia, and phosphorus control but also the psychological adjustment to dialysis.

Parathyroid enlargement at dialysis initiation in patients with chronic kidney diseases.

The kidney chiefly maintains homeostasis of water, electrolytes, and other solutions. When kidney function is reduced, mineral metabolism is disrupted. Mineral and bone disorder in patients with chronic kidney disease associates with increased cardiovascular risk and mortality; however, management of chronic kidney disease-mineral and bone disorder in predialysis patients remains controversial. This study investigates the association between parathyroid enlargement at dialysis initiation and hyperparathyroidism management in dialysis patients. We enrolled 72 patients at dialysis initiation in this study. Using parathyroid sonography, we categorized patients based on presence (detected group; N = 18) or absence (undetected group; N = 54) of enlarged parathyroid glands and assessed the clinical characteristics and laboratory findings. A literature review of ultrasound evaluations of secondary hyperparathyroidism was conducted. Ultrasonography revealed enlarged parathyroid glands in 18 patients (25%). Serum intact parathyroid hormone levels were high in patients with enlarged parathyroid glands; however, of the 29 patients with intact parathyroid hormone levels <240 pg/mL, four had enlarged parathyroid glands. Eight of the 29 patients with serum phosphorus and calcium levels within the optimal range had enlarged parathyroid glands. Twenty of these 29 patients were followed up at 38 ± 17 months (at least 3 months): enlarged parathyroid glands were detected in 6. During follow-up, serum intact parathyroid hormone levels were significantly higher in the detected group compared with the undetected. In conclusion, enlarged parathyroid glands are frequently detected at dialysis initiation, potentially predicting the persistence of secondary hyperparathyroidism and the need for strict management.

Development of Wernicke's encephalopathy during initiation of hemodialysis in an elderly non-alcoholic patient.

A 79-year-old man with chronic renal failure developed general fatigue and loss of appetite. He was diagnosed with endstage renal disease and was started on hemodialysis (HD). The symptoms improved immediately, but the mental status deteriorated gradually, reaching Glasgow Coma Scale (GCS) 5. Computed tomography showed no significant intracranial lesion, but magnetic resonance images showed symmetric high-intensity changes in the periaqueductal area, suggestive of Wernicke's encephalopathy (WE). He was immediately treated with intravenous infusion of thiamine. Five days later, the mental status level improved up to GCS 14, and the above MRI findings disappeared. To our knowledge, this is the first report describing the clinical outcome of a non-alcoholic patient who developed WE during initiation of HD. WE should be suspected in patients who are on chronic HD as well as those on initiation of HD with unexplained neurological abnormalities.

A case of cell-free and concentrated ascites reinfusion therapy effective for refractory ascites in spontaneous bacterial peritonitis in a renal transplant patient.

A 58-year-old Japanese male with chronic hepatitis C underwent kidney transplantation from an unrelated donor in October 1998. In December 2004, the patient was admitted for spontaneous bacterial peritonitis (SBP). Abdominal paracentesis and albumin transfusion were performed, but control of ascites was poor. A randomized, controlled study of patients with SBP showed that patients receiving cefotaxime with a high-volume albumin transfusion (50-75 g/50 kg) were significantly less likely to have irreversible renal failure and had lower mortality. Japan, however, relies on imports for 70% of its albumin formulations, which complicates high-volume albumin transfusion. Consequently, albumin transfusion is often limited to single treatments in the range of only 25 g (25%, 100 ml). A single cell-free and concentrated ascites reinfusion therapy (CART) treatment can reinfuse approximately 60 g of albumin, corresponding to a high-volume albumin transfusion capable of reducing the associated risk of infection or allergic reaction. Though this case was an SBP patient, after the ascites were found to be negative for endotoxins, CART was performed, and control of ascites was achieved without observation of fever, hypotension, or other adverse effects. CART provides greater supplementation of albumin than albumin transfusion and can be an effective modality of treatment for hypoalbuminemia in SBP patients if ascites are negative for endotoxins.

Remission of proteinuria and preservation of renal function in patients with renal AA amyloidosis secondary to rheumatoid arthritis.

BACKGROUND: Renal AA amyloidosis presents as a life-threatening disease in patients with rheumatoid arthritis (RA). Although several newly developed immunosuppressive drugs have been tried, patients often progress to end-stage renal failure with unsatisfactory survival rate. METHODS: A total of nine consecutive cases of severe nephrotic renal AA amyloidosis presented to us. Complete remission of proteinuria was observed in four cases (responders), and the remaining five reached the end point of haemodialysis or death (non-responders); these groups were retrospectively compared. The patients were treated with immunosuppressants, biological drugs and anti-hypertensive drugs. Levels of serum creatinine (S-Cr), urinary protein-creatinine ratio (UP/UCr), blood pressure (BP) and C-reactive protein (CRP) were measured. Histological characteristics of renal amyloid deposition and extent of kidney injury were also scored. RESULTS: Prior to treatment, clinical data (S-Cr, UP/UCr, BP and CRP) and histological severity (glomerular sclerosis, tubulointerstitial injury and extent of amyloid deposition) observed in the renal biopsy specimen were not significantly different between the groups. Following therapeutic intervention, proteinuria disappeared (UP/UCr <0.3) in responders within 12 ± 5.4 months but persisted in non-responders. Consequently, renal function stabilized in responders, but it deteriorated in all non-responders. Strict inflammatory control along with optimal control of hypertension was achieved in responders during the treatment. CONCLUSION: Regardless of histological severity, intensive therapeutic intervention that includes strict inflammatory control and optimal control of hypertension may change the histology-predicted prognosis of RA-associated renal AA amyloidosis.

Repeated Epstein-Barr virus-associated hemophagocytic syndrome in a lupus nephritis patient.

A 55-year-old Japanese female was diagnosed with systemic lupus erythematosus (SLE) and developed nephrotic syndrome. She was diagnosed with lupus nephritis by a percutaneous renal biopsy. She was treated with intravenous steroid pulse therapy twice, but it proved to be ineffective. She achieved a complete remission after intravenous cyclophosphamide pulse (CPAIV) therapy. Thereafter, her lupus nephritis was well controlled and demonstrated only a low activity. However, she suffered Epstein- Barr virus (EBV)-associated hemophagocytic syndrome (HPS) twice, and in each case she was treated with anticancer drugs and achieved a complete remission. This was a rare case of lupus nephritis who showed repeated EBV-associated HPS.

A new vasculitis activity score for predicting death in myeloperoxidase-antineutrophil cytoplasmic antibody-associated vasculitis patients.

BACKGROUND/AIMS: Myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA)-positive microscopic polyangiitis patients with renal involvement have been shown to have a progressive clinical course. In this study, we compared the clinical utility of the Japanese Vasculitis Activity Score (JVAS) with the Birmingham Vasculitis Activity Score (BVAS) for predicting death in patients with MPO-ANCA-associated renal involvement. METHODS: Sixty-nine patients with MPO-ANCA-associated vasculitis with renal involvement (22 males and 47 females, age 69.8 ± 8.7 years) were enrolled in this study. We retrospectively investigated which score was better for predicting the poor prognosis of patients. RESULTS: The mortality rate of the patients within 2 years after disease onset was 33% (23/69). JVAS was not correlated with BVAS. Univariate logistic regression analysis for death showed that the odds ratio (OR) of JVAS was statistically significant (OR 1.76, 95% confidence interval, CI, 1.29-2.41, p < 0.001), while that of BVAS was not (OR 1.07, 95% CI 0.98-1.16, p = 0.14). Moreover, a multivariate model showed that JVAS was an independent determinant of death (OR 1.59, 95% CI 1.12-2.25, p = 0.009). The area under the receiver operating characteristic curve for JVAS was 0.778, which was significantly larger (p = 0.02) than that for BVAS (0.586). The estimated optimal cut-off point of JVAS for the prediction of death was 5. At this point, the sensitivity was 82.6% and the specificity was 60.9%. CONCLUSION: We demonstrated that compared with BVAS, JVAS was a simpler and more reliable measure for predicting death in patients with MPO-ANCA-associated vasculitis with renal involvement.

Percutaneous renal artery embolization in a patient with severe nephrotic syndrome which continued after the introduction of hemodialysis.

We treated a woman with membranous nephropathy in whom serious nephrotic syndrome (NS) continued even after the introduction of hemodialysis (HD). No response was seen with conservative treatment, including administration of steroids and albumin transfusion and body fluid management with HD. Hypoalbuminemia continued, and management of her general condition was problematic because of the hypotension, edema, pleural and peritoneal effusions. We performed percutaneous renal artery embolization (RAE), voluntary urine output disappeared for a short time, and good clinical course was subsequently seen with sustainable serum albumin levels of around 3 g/dL.

Left ventricular mass index is an independent determinant of diastolic dysfunction in patients on chronic hemodialysis: a tissue Doppler imaging study.

BACKGROUND: Diastolic heart failure is the most common clinical form of heart failure. Tissue Doppler imaging (TDI) is often used to quantitate left ventricular (LV) diastolic function. The purpose of this study was to identify the determinant(s) of diastolic dysfunction in patients with end-stage renal disease on hemodialysis (HD), using the TDI method. METHODS: The study subjects were 53 patients with end-stage renal disease and preserved LV systolic function on maintenance HD. LV function was assessed by conventional echocardiography. The ratio of early trans-mitral flow velocity to early mitral annular velocity (E/e') was measured by TDI. Patients were stratified into two groups based on E/e' value (≤15 and >15 groups). Arterial stiffness was evaluated by pulse wave velocity and cardio-ankle vascular index. RESULTS: Patients of the E/e' >15 group were older (p = 0.025). There were no significant differences in blood pressure, ejection fraction, E/A, deceleration time, and pulse wave velocity between the E/e' >15 and E/e' ≤15 groups. However, there were significant differences in LV mass index (LVMI; p < 0.001) and cardio-ankle vascular index (p = 0.048) between the two groups. Multiple regression analysis identified that LVMI was an independent determinant of E/e' (p = 0.003). CONCLUSIONS: Our findings suggest that LVMI is an independent determinant of LV diastolic dysfunction in patients on HD.

Noninvasive monitoring of reproductive activity based on fecal progestagen profiles and sexual behavior in Koalas, Phascolarctos cinereus.

Studies on the reproductive endocrinology of koalas have been performed mainly by using blood samples; however, in practice it is difficult to collect blood periodically because koalas are easily stressed. The purposes of the present study were to establish a noninvasive endocrine monitoring technique and to investigate the reproductive physiology of female koalas. Feces were collected from female northern and southern koalas, and progestagen was extracted from lyophilized fecal samples and determined by enzyme immunoassay. In nonpregnant northern and southern koalas, fecal progestagen markedly increased after copulation and remained high for 36.3 +/- 2.5 days and 38.9 +/- 1.4 days (luteal phase, mean +/- SEM), respectively. Mean (+/-SEM) progestagen levels (6.34 +/- 0.49 microg/g) during the luteal phase in northern koalas were significantly higher than in southern koalas (4.19 +/- 0.24 microg/g). Fecal progestagen in parturient northern koalas remained high for 36.2 +/- 1.9 days (gestation period, 34.1 +/- 0.3 days). In northern koalas, the mean levels and profiles of progestagen during pregnancy (6.44 +/- 0.37 microg/g) were consistent with those during nonpregnancy after copulation (6.34 +/- 0.49 microg/g). The duration of behavioral estrus in northern koalas was 13.5 +/- 0.9 days without copulation. In contrast, when estrous females mated, the estrous sign disappeared just after copulation. The mean (+/-SEM) length of the estrous cycle in northern koalas, as determined by behavioral estrus intervals, was 33.5 +/- 2.2 days without the luteal phase and 69.2 +/- 7.6 days with the luteal phase. Fecal progestagen analysis is a helpful and noninvasive tool to monitor ovulatory activity in northern and southern koalas and could help us to understand the reproductive activity of koalas by the combination approach with behavioral estrus.

Obstructive acute renal failure related to amantadine intoxication.

We report the case of a 69-year-old woman with seizures and acute renal failure with hyperkalemia. She presented with bladder turgescence and hydronephrosis on admission and was diagnosed as obstructive acute renal failure. Urethral catheterization was performed after a single-session hemodialysis. It resulted in immediate improvement of renal function and consciousness, and subsequent disappearance of seizures. Improvement of serum creatinine level to 0.7 from 10.6 mg/dL was associated with a fall in blood level of amantadine hydrochloride from 4.40 to 0.47 microg/mL. Physicians should be aware of urinary retention in patients treated with amantadine as a first sign of intoxication that could lead if untreated to obstructive acute renal failure. And we recommend to check the overdose symptoms, even those with normal renal function, treated with amantadine.

[Clinical evaluation of tonsillectomy with modified high-dose intravenous methylprednisolone therapy in patients with IgA nephropathy].

Immunoglobulin A nephropathy (IgAN) is now recognized as the most common form of primary glomerulonephritis worldwide and is the major cause of end-stage renal disease. As reported, the renal survival rate is 61% at 20 years and the renal prognosis of this disease is relatively poor on long-term observation, hence various protocols have been attempted to control this disease. At Iizuka Hospital, a prospective study of tonsillectomy with methylprednisolone pulse therapy was performed for the treatment of patients with IgA nephropathy from August 2002. We reviewed the clinical efficacy of our protocol. From August 2002 to July 2006, 31 patients whose IgA nephropathy was demonstrated by percutaneous renal biopsy were administered our regimen. In our study, 12 patients had an observation period of more than 24 months. Our protocol consisted of tonsillectomy with one course of methylprednisolone pulse therapy. Methylprednisolone at the daily dose of 1,000 mg for 3 consecutive days followed by oral steroid at the daily dose of 20 mg, was gradually tapered, and discontinued one year later. All of the patients were administered angiotensin-converting enzyme inhibitors or angiotensin receptor blockers with favorable control of hypertension. The mean observation period for the 12 patients with IgA nephropathy was 37.4 months. The mean age at renal biopsy was 34.8 +/- 12.2 years. The male-female ratio was 3:9. At the renal biopsy in our hospital, mean creatinine value was 0.95 +/- 0.38 mg/dL, mean creatinine clearance was 92.1 +/- 34.9 mL/min, and the mean urinary protein and urinary creatinine ratio was 3.52 +/- 4.36. After 24 months, mean creatinine value was 1.03 +/- 0.59 mg/dL, mean creatinine clearance was 91.2 +/- 42.3 mL/min, and the mean urinary protein and urinary creatinine ratio was 0.83 +/- 0.98. Urinary protein and urine occult blood became negative in 66.7% of patients, and the urinary remission rate was 58.3%. On our protocol, mean length of the hospital stay was 11.4 +/- 4.7 days. Our prospective study showed that tonsillectomy with one course of methylprednisolone pulse therapy in IgA nephropathy appears to be beneficial for urinary remission and contributes to a short hospital stay.

[Steroid pulse therapy combined with tonsillectomy in a patient with IgA nephropathy complicated with tuberculous pleurisy].

We report a case of IgA nephropathy with tuberculous pleurisy that was treated with steroid pulse therapy combined with tonsillectomy. A 27-year-old female was referred to our hospital because of hematuria and proteinuria. Her urinalysis showed mild proteinuria (0.7 to 0.9 g/day) with dysmorphic red blood cells and cellular casts. Her serum creatinine level was within the normal range. Renal biopsy specimens revealed mild mesangial proliferation with cellular crescent and adhesion of glomeruli to the Bowman's capsule. Tubulointerstitial changes including mononuclear cell infiltration and tubular atrophy were also observed. Immunohistochemical staining of IgA and C3 was detected in the mesangial area, leading to the diagnosis of IgA nephropathy. She had a past history of tuberculous pleurisy at 13 years of age and had taken antituberculosis drug for one and a half year. Although treatment with angiotensin receptor antagonist was started, the amount of proteinuria was not changed. Steroid pulse therapy with tonsillectomy followed by oral prednisolone 20 mg/day was conducted. Proteinuria and hematuria gradually decreased. Her respiratory status and chest X-ray had been closely followed up by her respiratory physician. After one and a half years of treatment with low-dose prednisolone, her urinalysis became almost normal. Recurrence of tuberculosis was not observed during the follow-up period. The successful outcome of this case encouraged us to treat IgA nephropathy with a past history of tuberculosis using interventions including steroid pulse therapy.