Underweight and hypoalbuminemia as risk indicators for mortality among psychiatric patients with medical comorbidities.

AIM: Medical comorbidities are a major cause of death among patients with mental illness. The purpose of this study was to clarify the risk factors for mortality among psychiatric patients with medical comorbidities. METHODS: We retrospectively reviewed the clinical files of patients transferred to Tokyo Metropolitan Matsuzawa Hospital from a psychiatric hospital to treat medical comorbidities during the 3-year period from January 2014 to December 2016. We analyzed the clinical differences between the expired and alive patients. RESULTS: Of the 287 patients included, 29 (10.1%) had expired at the time of hospital discharge, while 258 (89.9%) were living. A multivariable analysis to determine the prognostic factors related to mortality from medical comorbidities showed that body mass index <18.5 had the highest odds ratio among the predictive factors (5.1; 95% confidence interval, 1.5-17.1; P < 0.05), followed by a serum albumin level < 3.0 mg/dL (3.0; 95% confidence interval, 1.1-8.1; P < 0.05). CONCLUSION: We found that underweight and hypoalbuminemia were risk factors for mortality among psychiatric patients with medical comorbidities. Physicians at psychiatric hospitals should consider transferring patients with medical comorbidities to a general medical hospital in the presence of underweight and/or hypoalbuminemia.

Estimation of BVAS in patients with microscopic polyangiitis in Japan.

The validity of the Birmingham Vasculitis Activity Score (BVAS) as an index of disease activity and a predictor of the prognosis and outcome in patients with MPA has not yet been established in Japan. We conducted a retrospective study of the data of 73 patients with MPA who were followed up for at least 2 years. We divided the patients into two groups according to the BVAS, namely, the high-BVAS group (≥16) and the low-BVAS group (<16), and compared the clinical characteristics. In addition, the distribution of the BVAS items in the patients and the items contributing to the total score in MPA patients were analyzed. Remission was achieved in 85% of patients at 1 month. There were no significant differences in the serum CRP, creatinine (Cre), or MPO-ANCA between the high- and low-BVAS group; however, the survival time was significantly shorter (p = 0.048) and the mortality rate significantly higher in the high-BVAS group (p = 0.04). The items of the BVAS contributing to the total score were motor neuropathy, sensory neuropathy, pulmonary infiltrate, hematuria, proteinuria, Cre ≥5.6 mg/dL, hypertension, scleritis, rise in Cre by ≥30%, and myalgia. BVAS was found to be a useful tool for determining the disease activity and outcome in patients with MPA in Japan. The initial BVAS was also predictive of the mortality and survival time and can also be used as a prognostic tool; therefore, use of the tool may facilitate the selection of appropriate treatment.

Clinical outcome and prognosis of anti-neutrophil cytoplasmic antibody-associated vasculitis in Japan.

BACKGROUND/AIMS: We conducted a broad survey of 99 patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis and investigated both prognosis and outcomes. METHODS: Clinical data evaluated were age, sex, patient survival, renal survival, serum albumin, serum creatinine, urinary protein, hematuria, C-reactive protein (CRP), ANCA titer, IgG and the Birmingham Vasculitis Activity Score (BVAS). RESULTS: The patient survival rate at 6 months after onset was 84.8%, and that at 2 years after onset was 82.0%. Most deaths were within 6 months of onset. Infection accounted for 9 deaths (60.0%). Infection together with pulmonary involvement of active vasculitis accounted for 2 deaths (13.3%). Organ-specific involvement of active vasculitis alone caused 3 deaths (20.0%). Others died of cardiac events. At 1 and 3 months after onset, BVAS (p < 0.0001, p = 0.002), albumin (p = 0.006, p = 0.0004) and CRP (p = 0.04, p = 0.0002) were also associated with patient death. CONCLUSION: To improve the prognosis of those with ANCA-associated vasculitis, the intensity of initial treatment should be aimed at disease severity. Employing BVAS improved the ability to evaluate therapeutic responses. Finally, prescription with sulfamethoxazole-trimethoprim during the induction therapy with immunosuppressive agents may be advised.

[Adult male with chronic renal failure due to reflux nephropathy that was possibly induced by neurogenic bladder since childhood].

A 38-year-old male with impaired renal function and serious anemia was admitted to our hospital. He had suffered from a disorder of urination since early childhood and been diagnosed as having neurogenic bladder by an urologist when he was 20 years old. Since February 2007, general fatigue emerged and gradually worsened. In addition, he began to feel nauseous around February 2008. He visited a family doctor and was diagnosed with renal failure and anemia both of which were serious. H e was referred t o our office and admitted immediately because his blood test showed a serum creatinine level of 4.4 mg/dL and hemoglobin of 3.1 g/dL. The initial study with ultrasonograhy suggested that both kidneys contained multiple cysts for the most part, likely due to hereditary polycystic kidney disease. However, a subsequent series of diagnostic imaging tests, including computed tomography and magnetic resonance urography, determined that the cause of renal failure was most likely reflux nephropathy due to secondary vesicouretral reflux induced by the chronic neurogenic bladder. Moreover, the upper gastrointestinal endoscopic examination showed that the cause of anemia was probably the persistent bleeding from gastric antral vascular ectasia. Reflux nephropathy emerges in early childhood and slowly progresses to chronic renal failure in some cases. According to the literature, it is not rare as a cause of end-stage kidney failure even among adult populations. Diagnostic imaging of severe reflux nephropathy is apparently similar to that of polycystic kidney disease. We herein present an adult male with chronic renal failure due to reflux nephropathy, the images of which were similar to polycystic kidney disease.

[Recurrence of severe hypophosphatemia associated with tumor neogenesis in a patient with acute lymphocytic leukemia who experienced acute renal failure due to tumor lysis syndrome].

We report a 47-year-old male patient with acute lymphocytic leukemia (ALL) who showed recurrent severe hypophosphatemia. Chemotherapy for ALL induced tumor lysis syndrome requiring hemodialysis therapy. Thereafter, severe hypophosphatemia (serum phosphorus concentration less than 0.7 mg/dL) was observed several days before an acute rise in peripheral lymphoblast cell counts due to recurrence of ALL. This hypophosphatemia soon returned to a higher than normal level by treating leukemic cells with anti-cancer agents. This event occurred twice in his clinical course. The laboratory tests strongly suggested that this hypophosphatemia was induced by a shift of phosphorus into leukemic cells that rapidly replicated in the tissues.

[Prevalence of chronic kidney disease (CKD) and significant contributors to CKD in HIV-infected patients].

We investigated the prevalence of CKD and factors associated with CKD in HIV-infected patients who were under stable medical control. We retrospectively abstracted the medical records of 748 HIV-infected outpatients(659 males and 89 females). Their mean age was 44.9+/-11.7 (range; 21 to 79) years. The following parameters were reviewed: urinalysis including proteinuria and microscopic hematuria, urinary N-acetyl-beta-glucosaminidase (NAG) level as a marker of tubular damage, serum creatinine level, estimated glomerular filtration rate calculated based on the Modification of Diet in Renal Disease formula (eGFR), CD4 count in peripheral blood, HIV-RNA copies in serum, use and vintage of highly active antiretroviral therapy (HAART), and use of anti-hypertensive drugs (AHTD). Stages of CKD were determined based on the K/DOQI stages of kidney disease. Chronic renal failure (CRF) was defined as an eGFR value of less than 60 mL/min/1.73 m2. The chi-square test was used to evaluate differences in the prevalence of dichotomous variables. Multivariable logistic regression analysis was applied to assess independent contributors to existence of CRF, proteinuria, and tubular damage. Proteinuria was positive in 50.0 % and hematuria was positive in 11.3 %. Both were positive in 8.41%. Tubular damage (> 11 U/L of urinary NAG levels) was positive in 42 out of 112(37.5 %). Prevalence of CKD and CRF was 87.8 % and 16.2 %, respectively. Stages of CKD were: stage 5D, 4 patients (0.53 %); stage 5, 0 patients (0%); stage 4, 3 patients (0.40 %); stage 3, 114 patients (15.2 %); stage 2, 487 patients (65.1%); stage 1, 49 patients (6.6%); and non-CKD, 91 patients (12.2 %). Statistically, use of HAART, urinary NAG level, and age were significant contributors to proteinuria. Proteinuria, age, and use of AHTD were strong predictors for CRF. Tubular damage was related to HAART vintage, age, and TG levels. In addition, HAART vintage of more than 2.5 years was statistically associated with the existence of tubular damage in HIV-infected patients. Prevalence of CKD in stable HIV-infected patients was unexpectedly high in our hospital. Aged patients with a long HAART vintage who have proteinuria and hypertension are predisposed to the development of CRF through tubular damage.

[Chronic renal failure in patients successfully treated with hematopoietic cell transplantation].

Recent development of hematopoietic cell transplantation (HCT) has greatly improved the quality of life in critical patients with hematological malignancies. On the other hand, it is a fact that some HCT survivors suffer from chronic renal failure (CRF). We attempted to examine the clinical characteristics of CRF in patients who were successfully treated with HCT in Japan. A retrospective analysis of 158 long-term survivors receiving HCT at Komagome Hospital was undertaken. CRF was designated as less than 30 mL/min of estimated GFR (eGFR) calculated by the MDRD formula. We statistically analyzed the influences of total body irradiation (TBI), graft versus host diseases (GVHD), renal impairment during HCT, new incidence of hypertension after transplantation, age, and gender on CRF, using the multivariate logistic regression analysis. Twenty-seven patients (17.1%) had CRF. Their mean ages were 33.1 +/- 8.87 years and mean eGFR levels were 20.5 +/- 9.50 mL/min/1.73 m2. Fifteen patients were recipients of TBI (55.6 %). CRF became obvious within one year after BMT in 5 patients (18.5%) and later in 22 patients (81.5%). Seven patients(25.9%) finally reached end-stage renal disease (ESRD) at the time of over 10 years after HCT. Multivariate logistic regression analysis showed that TBI, renal impairment during HCT, and new incidence of hypertension after HCT were significantly associated with CRF. Considering that 12 patients without TBI (44.4%) developed CRF, "renal impairment during HCT", the odds ratio of which was the highest, might be the factor most closely associated with CRF. The clinical course of a representative patient who developed ESRD was described. An increase in ESRD patients receiving HCT should be anticipated and would constitute a new important issue in nephrology.

A case report of thrombotic thrombocytopenic purpura and severe acute renal failure post non-myeloablative allogeneic peripheral blood stem cell transplantation treated with plasma exchange and hemodialysis.

A 59-year-old-woman received related non-myeloablative allogeneic peripheral blood stem cell transplantation (PBSCT) subsequent to autologous PBSCT in our hospital five years after she was diagnosed as oligo-secretory myeloma. She was admitted to our hospital because of vomiting and grayish diarrhea 4 months after non-myeloablative allogeneic PBSCT (mini-alloPBSCT). Although her initial symptoms improved after admission, she gradually showed thrombocytopenia, anemia, and oliguria during the 2 weeks after admission. Our diagnosis was thrombotic thrombocytopenic purpura (TTP) and acute renal failure (ARF) secondary to mini-alloPBSCT. After cessation of cyclosporine administration, we began to treat her with plasma exchange (PE) and hemodialysis. During the three and a half months after we started PE, the TTP gradually improved. Although PE had been reported to be ineffective for TTP post bone marrow transplantation, we could finally discontinue PE. In contrast, since her anuria continued, she was managed with hemodialysis. One month after PE was started, her activity of von Willebrand factor-cleaving protease was 41% (normal range, >50%) and the ultrasonographic investigation of both kidneys was normal. She could be discharged after four and a half months hospitalization and lived well as an outpatient for a further two months. She died shortly after readmission from multiple organ failure without the relapse of TTP. The patient's clinical course would suggest that TTP post mini-alloPBSCT could be treated with PE in some cases, despite the development of dialysis-requiring severe ARF being a poor prognostic factor.

[Nephrotic syndrome in patients after successful myeloablative allogeneic hematopoietic stem cell transplantation: clinical findings obtained from four transplanted patients].

We experienced four patients who suffered from nephrotic syndrome after a successful allogeneic hematopoietic stem cell transplantation (HSCT). These cases were seen in the nineteen-year period from September, 1986 to June, 2005. Our data showed that the incidence of nephrotic syndrome was 0.51% (3 out of 585 HSCT patients) in our hospital. Pathological findings of their renal biopsy specimens revealed that 3 patients had membranous nephropathy and that one patient had minimal change disease. Three patients were positive for anti nuclear antibody. Administration of prednisolone or cyclosporine improved the nephrotic syndrome, leading all patients to a complete or almost complete remission. The nephrotic syndrome occurred at 17 to 25 months after HSCT and accompanied the relapse of chronic graft-versus-host disease (GVHD), possibly due to the termination or a decrease of immunosuppressant administration in all patients. This suggests that immunological abnormality associated with chronic GVHD may be partly involved.

Tuberous sclerosis, associated with renal cell carcinoma and angiomyolipoma, in a patient who developed endstage renal failure after nephrectomy.

We report a case of tuberous sclerosis (TSC) associated with renal cell carcinoma and angiomyolipoma in a patient, who developed endstage renal failure that required hemodialysis after nephrectomy. A 37-year-old woman with TSC was admitted for further investigation of bilateral renal masses detected by computed tomography (CT). Angiography revealed a tumor stain (4 cm in diameter) in the medial portion of the right kidney. Because renal cell carcinoma (RCC) was strongly suspected, right nephrectomy was performed. Her serum creatinine level was already increased, moderately, at 2.4 mg/dl, before the right nephrectomy. Her renal function deteriorated quickly (in 1(1/2) years) after the right nephrectomy, and hemodialysis was introduced the next year. The histological findings of the resected right kidney revealed marked intimal thickening of the intralobular arteries. These findings suggested that the renal function loss was not only caused by the nephron mass reduction due to the nephrectomy but was also caused by nephrosclerosis. Though most patients with TSC die before developing endstage renal failure, this patient is currently receiving maintenance hemodialysis and has been followed for 3 years with no recurrence of RCC in the left kidney.

A female patient with malarial nephropathy.

Malaria remains one of the world's major health problems, particularly in developing tropical countries. Imported malaria is reportedly increasing in Western countries. Acute renal failure (ARF) is the most common cause of death in severe malaria. We report the case of a 63-year-old female patient with a history of travel to a rural area in South Africa who was in coma and had a high fever on admission. Thirty percent of her erythrocytes were infected with Plasmodium falciparum. She had cerebral malaria, malarial nephropathy, anemia, hepatic dysfunction, and disseminated intravenous coagulation (DIC). Quinine and artesunate treatment decreased the number of parasites in the blood. To manage renal failure, hemodialysis was performed for 11 days. A relationship between ARF and hepatic dysfunction was suggested. This relationship is an indication of the clinical course of the disease. In this article, we discuss the mechanism underlying the development of malarial nephropathy and its management, particularly the usefulness of hemodialysis.

Role of cytokines in anaphylactoid reaction with marked eosinophilia in a hemodialysis patient.

Hemodialysis is rarely terminated by events associated with anticoagulants. A 69-year-old woman on hemodialysis due to chronic renal failure (CRF) developed an anaphylactoid reaction with hypereosinophilia. On the basis of clinical and laboratory findings, we concluded that the causes of this anaphylactoid reaction were low-molecular-weight heparin and heparin. Our patient also showed high levels of soluble interleukin-2 receptor (sIL-2R) and eosinophil cationic protein (ECP), which decreased after the cessation of hemo-dialysis. To date, there has been no report of high levels of cytokines induced by hemodialysis-associated anaphylactoid reaction. In this report, we discuss the mechanism underlying drug-induced anaphylactoid reaction, particularly that involving eosinophilia and cytokines.

Role of mitogen-activated protein kinase in the regulation of transforming growth factor-beta-induced fibronectin accumulation in cultured renal interstitial fibroblasts.

BACKGROUND: In diabetic nephropathy, tubulointerstitial fibrosis is an important component of renal injury. Transforming growth factor (TGF)-beta is a key cytokine that is involved in the pathogenesis of tubulointerstitial fibrosis. However, signal transduction cascades of TGF-beta under high-glucose conditions remain to be clarified. We undertook this study to elucidate whether mitogen-activated protein (MAP) kinase and Smad proteins were involved in TGF-beta-induced fibronectin (FN) production under high glucose in NRK fibroblasts. METHODS: After serum restriction, NRK cells were exposed to either normal glucose (5.5 mM d-glucose), high glucose (30 mM d-glucose), or 30 mM l-glucose in the presence or absence of TGF-beta for 24 h. MAP kinase inhibitors (SB 203580 and PD 98059) were added to the cultured NRK fibroblasts 2 h before TGF-beta1, and the incubations continued for 8 h. The phosphorylation of p38 MAP kinase, extracellular signal-regulated kinase (ERK)1/ERK2, and c-Jun N-amino terminal kinase (JNK) was assessed by immunoblotting. Reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting were performed to determine FN mRNA and protein expression, respectively. RESULTS: High glucose significantly increased the expression of FN mRNA, by 2.4 +/- 1.4-fold. In the presence of either SB 203580 or PD 98059, the high glucose-induced FN mRNA increase was completely inhibited. Incubation of NRK fibroblasts for 48 h in 30 mM d-glucose did not alter p38 MAP kinase, ERK1/ERK2, or JNK phosphorylation. The addition of exogenous TGF-beta1 (1 ng/ml) for 8 h increased FN mRNA by 2.7 +/- 1.1-fold. Both the TGF-beta1- and high glucose-induced FN mRNA increases were inhibited by SB 203580 and PD 98059. Dominant-negative Smad4 did not affect the FN mRNA increase induced by TGF-beta1 and high glucose. Exogenous TGF-beta1 under both normal and high glucose, enhanced the phosphorylation of both p38 MAP kinase and ERK1/ERK2, but not that of JNK. CONCLUSIONS: NRK fibroblasts exposed to high glucose demonstrated increased TGF-beta1-induced p38 MAP kinase activation. The FN synthesis induced by high glucose and TGF-beta1 was not affected by the Smads pathway and was not due to increased osmolarity. The enhanced activation of p38 MAP kinase may contribute to the altered fibroblast phenotype that leads to progressive diabetic nephropathy.