Naohiko Imai

Distinct roles of urinary liver-type fatty acid-binding protein in non-diabetic patients with anemia.

Background Various stresses including ischemia are known to up-regulate renal L-FABP gene expression and increase the urinary excretion of L-FABP. In diabetic patients with anemia, the urinary excretion of L-FABP is significantly increased. We studied the clinical significance of urinary L-FABP and its relationship with anemia in non-diabetic patients. Subjects and Methods A total of 156 patients were studied in this retrospective cross-sectional analysis. The associations between anemia and urinary L-FABP levels, and the predictors of urinary L-FABP levels in non-diabetic patients were evaluated. Results Urinary L-FABP levels were significantly higher in patients with anemia compared to those in patients without anemia. Similarly, the urinary L-FABP levels were significantly higher in patients with albuminuria compared to those in patients without albuminuria. Urinary L-FABP levels correlated with urinary albumin-to-creatinine ratios, estimated glomerular filtration rates, body mass index, and hemoglobin levels. Multivariate linear regression analysis determined that hemoglobin levels (β = -0.249, P = 0.001) and urinary albumin-to-creatinine ratios (β = 0.349, P < 0.001) were significant predictors of urinary L-FABP levels. Conclusions Urinary L-FABP is strongly associated with anemia in non-diabetic patients.

Safety of Monitoring Viral and Liver Function Markers in Patients With Prior Resolved Hepatitis B Infection After Kidney Transplantation.

BACKGROUND Hepatitis B virus (HBV) infection is a risk factor of mortality in kidney transplant recipients. However, information on the risk of HBV reactivation in kidney recipients with prior resolved HBV infection is limited. This study aimed to evaluate the safety of simply monitoring viral and liver markers in living donor kidney transplantation (LDKT) recipients with prior resolved HBV infection. METHODS We retrospectively examined the clinical records of LDKT recipients. Changes in the levels of alanine aminotransferase, aspartate aminotransferase, hepatitis B surface antigen (HBs Ag), surface antibody, core antibody, and HBV-DNA after transplantation were evaluated, and the occurrence of de novo HBV-related hepatitis and allograft function were monitored. RESULTS Of 61 consecutive LDKT patients, seven had prior resolved HBV infection. Four patients underwent ABO-compatible LDKT, whereas two underwent ABO-incompatible LDKT. The median age was 64 years (range, 61-69 years), and two patients were women. The causes of end-stage kidney disease were diabetic nephropathy, hypertensive nephrosclerosis, and chronic glomerulonephritis. Five patients were referred to hepatologists. The history of HBV vaccination was not confirmed in all patients. Prophylaxis with entecavir was administered to two patients with ABO-incompatible LDKT before transplantation. All patients tested negative for HBs Ag and HBV-DNA throughout observation, and none developed de novo HBV-related hepatitis or graft loss. CONCLUSIONS Patients with HBV infection without HBV DNA positivity are eligible for kidney transplants without antiviral therapy, even those on rituximab therapy. Monitoring viral and liver markers combined with hepatologist consultations may ensure safe follow-up in LDKT recipients with prior resolved HBV infection.

Urinary Tract Reconstruction Using Uretero-Ureteral End-To-Side Anastomosis in Kidney Transplant Recipients

BACKGROUND In kidney transplant recipients, the most widely used method for the reconstruction of the urinary pathway is ureteroneocystostomy, which may be difficult in cases with disused atrophic bladder. In this study, we evaluated kidney transplant recipients who underwent uretero-ureteral end-to-side anastomosis (UUA) in urinary reconstruction due to disused atrophic bladder. METHODS To clarify the effectiveness of this method, we retrospectively reviewed the clinical records of kidney transplant recipients in our hospital. RESULTS A total of 9 recipients with urinary reconstruction using UUA were evaluated. All of these patients had a history of long-term hemodialysis before transplantation, accompanied by complete anuria and small capacity of the bladder. In 4 patients, cranial native ureter was ligated, whereas it was not ligated in the remaining 5 patients. In 2 of 4 patients with cranial ligation, hydronephrosis developed in the native kidney with no further treatment being required. No patients experienced urinary tract complications including hydronephrosis in the graft, urine extravasation, or urinary tract infection in the follow-up period (757.6 ± 491.3 days). Allograft function was maintained well in all patients (serum creatinine level, 1.08 ± 0.23 mg/dL). CONCLUSIONS Although UUA is not a routine method of urinary reconstruction in kidney transplantation, it can be safely performed and should be a surgical option, especially for recipients with disused atrophic bladder. The ligation of cranial native ureter may lead to hydronephrosis of the native kidney, and it is tentatively concluded that UUA without native ureteral ligation is clinically feasible.

Challenges for Preventing the Metabolic Syndrome in Kidney Transplant Recipients, Initial Report: Survey of the Current State of Affairs Before Acting

OBJECTIVE To prevent the metabolic syndrome preventive in kidney transplant recipients, we measured changes in body composition parameters using bioelectrical impedance analysis (BIA), and measuring renal function, blood tests, quality of life, and consciousness of life improvement. The usefulness of BIA was investigated. SUBJECTS AND METHODS Out of all kidney transplant recipients being treated at an outpatient clinic, 20 (13 males and 7 females) gained ≥ 5 kg after transplantation. We investigated changes after 6 months of physical activity versus initiation. RESULTS After the initiation of body composition parameters using BIA, consciousness of life improvement changed, and measured body composition values and blood data did not worsen. Both systolic and diastolic blood pressures tended to decrease after initiation. CONCLUSIONS Detailed visualization of body composition in addition to the body weight and body mass index, as well as guidance based on the results promoted changes in consciousness, enhanced self-efficacy, and increased motivation for the prevention of the metabolic syndrome, suggesting that BIA is a useful tool in the management of weight gain after kidney transplantation.

Nutcracker phenomenon in IgA nephropathy.

IgA nephropathy is the most common cause of idiopathic glomerulonephritis in the developed world. Although this disorder was initially thought to follow a benign course, it is now recognized that slow progression to end-stage renal disease occurs in up to 50% of affected patients. The two major clinical presentations of IgA nephropathy are gross hematuria and persistent asymptomatic microscopic hematuria with or without mild to moderate proteinuria, which can also be seen in nutcracker syndrome caused by nutcracker phenomenon. The nutcracker phenomenon refers to the compression of the left renal vein between the abdominal aorta and the superior mesenteric artery with impaired blood outflow accompanied by distention of the distal portion of the vein. Nutcracker syndrome is the clinical manifestation of nutcracker phenomenon characterized by a wide spectrum of symptoms, such as hematuria, orthostatic proteinuria, pain or gonadal vein syndrome, and varicoceles.

A case of Campylobacter enteritis in a renal transplant recipient.

A 28-year-old man who underwent living-donor kidney transplantation in November 1998 was admitted to our hospital with a fever of 100.2-F (37.9-C) and multiple episodes of nonbloody, watery stools. The patient had been well until 3 days before admission, when he developed high fever, shaking chills, right abdominal pain, and watery stools without nausea or vomiting, all of which gradually progressed. He lost his appetite and experienced unintentional weight loss of more than 3 kg. He denied having traveled recently or changing his usual dietary habits or potable water supply, and no other household members were ill. His immunosuppressive medications included azathioprine 50 mg, cyclosporine 175 mg, and methylprednisolone 4 mg. His major medical and surgical history included end-stage renal disease due to unknown cause, asthma, cataracts, and glaucoma. On admission, the patient’s temperature was 100.2-F (37.9-C), systolic blood pressure was 60 mm Hg, heart rate was 130/min, respiratory rate was 20/min, and oxygen saturation was 98% on room air. He was fully alert and oriented. His skin was dry. His abdomen was soft and flat with mild tenderness in the right lower quadrant; Murphy’s sign and heel drop tests were negative. The remainder of the physical examination was unremarkable. The patient’s laboratory test results showed total white blood cell count of 7.6 10 cells/mL, hemoglobin 15.5 g/dL, urea nitrogen 39.3 mg/dL, and serum creatinine 3.2 mg/dL (baseline 1.0 mg/dL). Intravenous hydration was started. Urine and blood cultures were obtained at that time. A computed tomography scan of the abdomen without the administration of contrast material showed wall thickening of the ileocecal area and ascending colon. Results of urinalysis and stool studies for ova, parasites, and enteric pathogens including Clostridium difficile were negative. Stool samples were plated on charcoal-based selective medium agar in a microaerobic environment for the detection of Salmonella, Shigella, and Campylobacter. After admission, his fever showed some improvement, as did the frequency of the diarrhea. On the seventh day of hospital stay, he again had a temperature of 103.1-F (39.5-C) and his diarrhea worsened. Colonoscopy (Fig. 1) showed an ileocecal ulcer, and an intestinal mucosa biopsy was then performed to enable bacterial and mycobacterium cultures. The stool culture results detected Campylobacter jejuni, which was sensitive to several antimicrobial classes; therefore, he was started on oral azithromycin for 3 days. Subsequently, the intestinal mucosa culture results also revealed C. jejuni. Blood culture results were negative for C. jejuni. After initiation of antibiotics, the patient became afebrile and asymptomatic. On the 18th day of hospital stay as he remained afebrile and asymptomatic, he was discharged. Although Campylobacter species are the most commonly identified bacterial causes of food-borne acute gastroenteritis in humans, only a few cases of Campylobacter enteritis, including Campylobacter bacteremia, have been reported in renal transplant recipients (Table 1) (1Y5). Campylobacter jejuni is one of the two major Campylobacter species, and unlike other enteric infections, such as Shigella or Salmonella, Campylobacter infection is only rarely associated with systemic invasive illness (6Y8). Contaminated meat, poultry, and water represent the main reservoirs of human infection. As in this case, gastrointestinal system disorders, such as diarrhea, are frequently observed after transplantation and are an important complication in organ transplant recipients (9). Campylobacter jejuni should always be considered in the differential diagnosis as a potential cause of enteritis in immunosuppressed renal transplant patients presenting with FIGURE 1. Colonoscopy showed an ileocecal ulcer.

Asymptomatic post-transplant lymphoproliferative disorder diagnosed at one year protocol renal allograft biopsy.

Post‐transplant lymphoproliferative disorder (PTLD) is a neoplastic complication with a potentially fatal outcome that develops as a consequence of immunosuppression, and is mainly associated with Epstein‐Barr virus (EBV) infection. A 70‐year‐old woman underwent a live unrelated, ABO‐incompatible renal transplant for end‐stage renal disease. One year after transplantation, protocol biopsy revealed pathological changes indicative of the histological subtype of ‘early lesions of PTLD’ according to the World Health Organization classification, while the patient showed no clinical signs or symptoms. The patient was finally diagnosed with EBV‐positive PTLD by in situ hybridization for EBER (EBV‐encoded RNA), and was successfully treated based on the reduction of immunosuppression. Protocol biopsy within the first post‐transplant year is the only diagnostic measure to detect asymptomatic early PTLD, which allows for early intervention and leads to better outcomes.

Encapsulating peritoneal sclerosis with steroid-resistant massive ascites successfully treated by peritoneal lavage

Encapsulating peritoneal sclerosis (EPS) is the most serious complication of long-term peritoneal dialysis (PD). EPS is diagnosed by clinical symptoms (abdominal pain, nausea, vomiting, diarrhea, and anorexia.) and image study (intestinal expansion, peritoneal thickening and calcification, and ascites.). Steroid therapy and surgery are recommended as the treatment of EPS. Here, we report a case of EPS with steroid-resistant massive ascites successfully treated with peritoneal lavage. A 59-year-old female with end-stage kidney disease secondary to hypertension was started on PD in 2003. Due to recurrent exit-site infection and two episodes of peritonitis, she was transferred to hemodialysis (HD), and her PD catheter was removed in 2011. In February 2012, six months after discontinuation of PD, she was found to have massive ascites on abdominal computerized tomography (CT). The patient was diagnosed to have EPS and was started on prednisolone. Despite eight months of prednisolone therapy, the ascites did not decrease. Therefore, the PD catheter was inserted again, and she was started on daily peritoneal lavage from September 2012. After four months of daily peritoneal lavage, her ascites disappeared in January 2013. The PD catheter was removed in July 2013. Steroid treatment was completed in May 2014, and there has been no recurrence of ascites since then. The evaluation of ascites by abdominal CT is important in a patient on long-term PD. Since EPS may appear any time after the discontinuation of PD, it is important to start screening abdominal CT shortly after the discontinuation of PD. Steroid-resistant massive ascites can be successfully treated with peritoneal lavage.

Can nutcracker phenomenon cause glomerular hematuria?: Can nutcracker phenomenon cause glomerular hematuria?

We present a 41-year-old Japanese male with proteinuria and microhematuria for 10 years referred for evaluation. There was no family history of hematuria nor kidney disease. Abdominal ultrasonography revealed compression of the left renal vein between the aorta and the superior mesenteric artery. The maximum velocity of the left renal vein was elevated and the diagnosis of nutcracker phenomenon was made. Laboratory tests showed serum creatinine of 1.0 mg/dL and minimal proteinuria of 0.2 g/gCr. Urine sediment analysis showed the presence of dysmorphic red blood cells (20–29/HPF) and red blood cell casts. Kidney biopsy was performed for the evaluation of glomerular hematuria. Light microscopy revealed the presence of red blood cells in glomeruli as well as in the Bowman’s capsule (Fig. Fig. 1). The glomerular basement membrane was intact, and the proliferation of mesangial and endothelial cells was not observed. Tubulointerstitial fibrosis was mild, and vascular lesions were not present. Direct immunofluorescence stainings were negative, and electron microscopy findings were unremarkable. The glomerular hematuria observed in our patient was thought to be caused by nutcracker phenomenon. Nutcracker phenomenon is a well-known cause of nonglomerular hematuria. The mechanism for producing nonglomerular hematuria is not fully understood but it has been postulated that increased left renal vein pressure results in small venous ruptures into the collecting system causing non-glomerular hematuria. Nutcracker phenomenon has been reported to coexist with glomerular disease, especially IgA nephropathy. Thus, glomerular hematuria seen in nutcracker phenomenon has been attributed to glomerular disease. Although further studies are needed, our case suggests the possibility that increased left renal vein pressure seen in nutcracker phenomenon could results in glomerular hematuria as well. Nutcracker phenomenon should also be kept in mind when evaluating a patient with glomerular hematuria.

Emphysematous cystitis and spontaneous sigmoid colon perforation in a patient with steroid-dependent nephrotic syndrome

Focal segmental glomerulosclerosis (FSGS) is one of the major causes of refractory nephrotic syndrome (NS). The main treatment strategy for FSGS is steroid therapy but steroid has many adverse effects (AE) and the risk increases with duration of steroid administration. We present a 65-year-old Japanese woman with chronic kidney disease stage G5A3 due to FSGS. Her course was complicated by repeated relapses and the administration period of steroid became prolonged as it became difficult to control. This time she was admitted under treatment of 6 relapse. On admission, elevation of inflammatory response was observed. Screening computed tomography (CT) was performed and emphysematous cystitis was detected. After insertion of transurethral catheter antibiotic therapy was started and the cystitis was treated successfully. On the 30 day, the patient complained of acute severe lower midabdominal pain. Again, screening CT was performed and the perforation of sigmoid colon was suspected (Fig. 1). She underwent emergency exploratory laparotomy and perforation of sigmoid colon was confirmed. The sigmoid was resected and an artificial anus was created. The postoperative course was noted for poor wound healing. Cumulative dose of steroid is known to be strongly associated with AE, especially when the cumulative dose exceeds 10 000 mg (prednisolone conversion). In our case, the cumulative dose well exceeded 10 000 mg. Steroid carries a risk of emphysematous cystitis but spontaneous perforation of the digestive tract is rare. Our patient was symptomatic and we were able to diagnose promptly, but long-term steroid administration can mask symptoms. We need to have low threshold for performing CT not only to detect severe complications early but also to prevent them.