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Rhabdomyolysis is a rare perioperative complication, however, potentially lead to fatal outcome. We experienced 2 cases of rhabdomyolysis after radical nephrectomy and nephroureterectomy in the lateral decubitus position. (Case 1) A 40-years old man was seen in our hospital because of asymptomatic grosshematuria. Computed tomography revealed right renal pelvic cancer, cT3N0M0. Right radical nephroureterectomy, lymph node dissection, partial cystectomy was underwent, and the operation was finished without any trouble. At the post-operative day 1, serum creatinine level was elevated to the point of 4.2 mg/dl, and serum creatine kinase was 1,945 IU/l. Continuous hemodiafiltration (CHDF) was done at intensive-care unit (ICU), and serum creatinine and creatine kinase level were decreased. At the post-operative day 1, urine myoglobin level was prominently elevated (2,943.7 ng/ml), so we diagnosed acute renal failure due to rhabdomyolysis. (Case 2) A 40-years old man was incidentally pointed out of right renal tumor that was seen as renal cell carcinoma, cT1aN0M0. Open partial nephrectomy was underwent, and there was no trouble during the operation. After recovering from anesthesia, the patient felt left thigh pain strongly. Serum creatine kinase was 888 IU/L after the operation. At the postoperative day 1, serum creatine kinase level was markedly increased (31,138 IU/L). Serum creatinine level was 1.34 mg/dl. Urine and serum myoglobin level was prominently elevated (89,000 ng/ml and 8,634 ng/ml, respectively). We diagnosed it rhabdomyolysis, and he received large amount of fluid intravenously at intensive-care unit. Serum creatine kinase was peak out at the post-operative day 3 (20,709 IU/L), and hemodialysis was not performed.

We report a 35 month-old boy with acute renal failure caused by an obstructive ureteral stone associated with norovirus gastroenteritis. He visited his family physician because of fever, abdominal pain and vomiting. He was diagnosed as acute gastroenteritis. The symptoms relieved once, but abdominal pain and vomiting recurred two days after the visit and the volume of urine decreased. He was diagnosed as norovirus gastoenteritis and acute renal failure which was unresponsive to fluid replacement. Ultrasound study of the abdomen showed a solitary kidney with mild hydronephrosis. He was then admitted to our hospital. He was finally diagnosed as acute postrenal failure due to obstructive ureteral stone with left solitary kidney by abdominal computer tomography (CT). We performed transurethral catheterization immediately. The creatinine and blood urea nitrogen returned to normal level in 2 days. The CT performed on the 28th day post operation showed disappearance of the stone after uric alkalization. Recently, some cases of postrenal failure due to bilateral obstructive ureteral stones, mainly ammonium acid urate stones, associated with viral gastroenteritis were reported. As clinical features, they are common in boys three years or younger after an episode of rotavirus gastroenteritis with high uric acid concentration. By far, the most common cause of acute renal failure in patients with severe gastroenteritis is prerenal failure resulting from hypovolemia. But postrenal cause due to bilateral obstructive stones should be taken in a consideration.

A 62-year-old-Japanese man had a history of probable granulomatosis with polyangiitis (GPA) from 7 years previously, showing kidney and vasculitis symptoms with PR3-ANCA (864 EU) without renal biopsy. Remission with normalization of renal function and urinary findings was induced by corticosteroid therapy. Prednisolone (PSL) was tapered to 5 mg/day and maintained for 6.5 years with a low positive titer of PR3-ANCA. After 7 years of remission, he was referred to our hospital because of arthralgia, fever, general fatigue and appetite loss with apparent urinary abnormality, increased serum Cr (1.8 mg/dL) and C reactive protein (CRP : 30.1 mg/dL). On admission, he showed a high titer of PR3-ANCA (> 300 U/mL). Renal biopsy demonstrated the existence of the pauci-immune type of severe crescentic necrotizing glomerulonephritis, tubulo-interstitial damage and perivascular granuloma. He was diagnosed as relapse of GPA (kidney-localized type) without upper respiratory tract (E) and lung (L) symptoms. Accordingly, he received steroid pulse therapy leading to improvement of these symptoms and renal function. Oral PSL at the dosage of 40 mg/day was administered after steroid pulse therapy, and then tapered to 20 mg/day. Cyclophosphamide was added within 8 weeks. He was discharged 8 weeks after treatment with a decreased level of Cr (1.5 mg/dL) and PR3-ANCA (244 U/mL). After discharge, PSL was tapered to 10 mg/day during the course of stability resulting in a further improved level of Cr (1.2 mg/dL), PR3-ANCA 40 U/mL in the outpatient clinic. In Japan, PR3-ANCA-positive GPA has a lower incidence than MPO-ANCA-positive microscopic vasculitis. In GPA, the kidney-localized (K) type without upper respiratory tract (E, L) symptoms is rare. Histologically, not only necrotizing crescentic glomerulonephritis but also perivascular granuloma in the kidney are very rare and interesting.

Liver-type fatty acid binding protein (L-FABP) is a 14kDa protein found in the cytoplasm of human renal proximal tubules. Fatty acids are bound with L-FABP and transported to the mitochondria or peroxisomes, where fatty acids are beta-oxidized, and this may play a role in fatty acid homeostasis. Moreover, L-FABP has high affinity and capacity to bind long-chain fatty acid oxidation products, and may be an effective endogenous antioxidant. Renal L-FABP is rarely expressed in the kidneys of rodents. In order to evaluate the pathological dynamics of renal L-FABP in kidney disease, human L-FABP chromosomal transgenic mice were generated. Various stress, such as massive proteinuria, hyperglycemia, hypertension, and toxins overloaded in the proximal tubules were revealed to up-regulate the gene expression of renal L-FABP and increase the excretion of L-FABP derived from the proximal tubules into urine. In clinical studies of chronic kidney disease (CKD), urinary L-FABP accurately reflected the degree of tubulointerstitial damage and correlated with the rate of CKD progression. Furthermore, a multicenter trial has shown that urinary L-FABP is more sensitive than urinary protein in predicting the progression of CKD. With respect to diabetic nephropathy and acute kidney disease (AKI), urinary L-FABP is an early diagnostic of kidney disease or a predictive marker for renal prognosis. After many clinical studies, urinary L-FABP was approved as a new tubular biomarker promulgated by the Ministry of Health, Labour and Welfare in Japan.

The patient was an 82-year-old female. She had been treated with warfarin for atrial fibrillation that developed after a heart valve replacement operation. She was admitted because of a progressive loss of renal function together with persistent microscopic hematuria and proteinuria. Although the renal biopsy showed only focal mononuclear cell infiltration and mild mesangial expansion in the glomeruli, the occlusive red blood cell casts were remarkable in the tubules and were accompanied by inflammatory and edematous changes in the surrounding interstitial area. After the adjustment of an excessively extended prothrombin time, her renal function gradually improved in parallel with the marked decrease in the microhematuria. It was assumed that an acute kidney injury observed in this case was caused by the occlusive red blood cell casts as a result of abnormal hemorrhage in the glomeruli due to focal glomerulonephritis and a warfarin overdose. The present case, therefore, suggests that a warfarin overdose is a potential risk factor for acute kidney injury in the presence of coexisting glomerular injury.

Objective: Few findings are available regarding adult-onset minimal change nephrotic syndrome (MCNS) with respect to the disease course and complications, such as acute kidney injury (AKI). We therefore performed a retrospective review to characterize the clinical presentations, steroid responsiveness and complications of adult-onset MCNS patients in our hospital., Patients and Methods: We retrospectively reviewed 40 cases of idiopathic adult-onset MCNS who had been investigated and treated at a single center. Patients between 18 and 50 years of age (Younger group) at the time of biopsy were compared with those older than 50 years (Older group) with regard to demographic data, clinical features and treatment outcome., Results: Baseline characteristics of the 40 patients were: median age, 42 years (interquartile range: 28-63 years); male, 70%; mean (+/- standard deviation) systolic and diastolic blood pressures, 125 +/- 17 mmHg and 78 +/- 12 mmHg, respectively; estimated glomerular filtration rate (eGFR), 74 mL/min/1.73 m2 (range: 64-94 mL/min/1.73 m2); serum albumin, 1.8 +/- 0.3 g/dL; and urinary protein, 7.8 g/day (range: 3.9-10.4 g/day). All except for one patient received steroid pulse therapy. Time to complete response (CR) was 12 days (range: 8-21 days). Time to CR was significantly longer in the Older group (p = 0.011). The Late-responder group (time to CR > 2 weeks)was significantly older (p < 0.01), with a low eGFR (p < 0.001) and a higher prevalence of interstitial fibrosis in renal biopsy before the initiation of corticosteroid therapy (p < 0.05), compared with the Early-responder group. AKI was observed in 14 patients. Patients with an episode of AKI were significantly older (p = 0.005), with a lower eGFR (p < 0.002) and a higher prevalence of cellular casts (p < 0.05). At the follow-up, 19 patients (51%) had experienced relapses. The relapse rate was significantly lower in the Older group than in the Younger group (p < 0.05)., Conclusion: The present study revealed that older patients had a longer period to CR and a higher risk of AKI at follow-up.

Thioredoxin (TRX) is a redox-regulating protein, induced in response to oxidative stress. The function of TRX in the urine is unknown. We show here that urinary TRX begin to increase within one hour and peaks within two hours after ischemia reperfusion of mice. Serum levels of TRX are not changed by the ischemia/reperfusion. In a time-dependent study of immunohistochemistry, TRX appears diffusely in the tubular cytosol in sham-operated mice. On the other hand, immediately after renal ischemia/reperfusion, TRX become to eccentrically-locate in the apical side of the tubular cytosol, and then TRX is detected only in the urinary lumen. In contrast, when we examine the immunolocalization of glutaredoxin, which is a member of the TRX superfamily, we find that the immunoreactivity is unchanged after renal ischemia/reperfusion. Northern blotting and in situ hybridization show that epithelial cells constitutively express TRX mRNA but neither expression levels nor distribution are altered by ischemia-reperfusion. An overexpression of hTRX in transgenic mice attenuates the reperfusion injury. These data suggests that TRX is produced in tubular cells in a steady state. The increase in the urine after ischemia-reperfusion is not mediated by a de novo induction of TRX mRNA but by a discharge of TRX protein from tubular epithelial cells. TRX is useful for the diagnosis of AKI in association with oxidative stress.

We report a case of suspected pseudo-elevation of serum creatinine in a patient with rheumatoid arthritis, whose blood sample was obtained from his right cubital vein immediately after the intra-articular injection of 0.67 mg of a pharmaceutical preparation of dexamethasone (Decadron) containing creatinine as a buffer into his right wrist joint to alleviate arthralgia. The 61-year-old male patient, who had been treated for rheumatoid arthritis, was referred to our outpatient clinic by his family doctor because of sudden elevation of his serum creatinine, which hitherto had been normal. Acute kidney injury (AKI) was suspected, but his medical history, physical examinations, and laboratory findings did not support the diagnosis of AKI. The preserved serum sample obtained when the elevation of his serum creatinine was reported was examined and revealed that the serum concentration of cystatin C was normal, but the serum concentration of creatinine measured with high-performance liquid chromatography method was elevated to a degree consistent with the serum creatinine concentration measured with enzymatic method. Accordingly, we predicted the possibility that creatinine contained in Decadron as a buffer was included in the measurement of his intrinsic serum creatinine. To test this hypothesis, the creatinine concentration of serum samples from another patient with known amounts of added Decadron were measured, and the additive effect of the extrinsic creatinine in the measurement of serum creatinine concentration was confirmed. These findings clearly suggest that we should consider the influence of extrinsic creatinine as an inactive ingredient in the measurement of serum creatinine.

Objective: Myeloablative (m-allo) hematopoietic stem cell transplantation (SCT) involves a great risk of acute kidney injury (AKI). We assessed whether or not early elevation of urinary biomarkers is useful for identifying high-risk patients for AKI., Material and Methods: A prospective cohort study was conducted in 40 patients (46.0+/-12.5 years, eGFR 96.1 +/- 25.3 mL/min/1.73 m2) who received m-allo SCT in our hospital. We measured urinary biomarkers such as N-acetyl-beta -glucosaminidase (NAG), beta2 microglobulin (beta 2M), alpha microglobulin ( alpha1M) before conditioning therapy, on the day of SCT and both days 7 and 14 after SCT. AKI was defined as a decrease in eGFR within 100 days after SCT, and classified based on the RIFLE criteria. Discriminative sensitivity of urinary biomarkers was estimated using area under receiver operating characteristic (AuROC) curve analysis., Results: AKI occurred in 28 cases(70 %): risk was 25.0 %, injury was 17.5 %, failure was 22.5 % and loss was 5.0 %, respectively. Only 4 cases with AKI > or = injury that occurred less than 40 days after SCT died within 100 days after SCT. Thus, this level of AKI was denoted as"severe AKI"and targeted for early identification. Values of all urinary biomarkers increased gradually after the conditioning therapy, and both NAG and alpha 1M values at day 7 became significantly higher in the severe AKI group than in the opposite group. The AuROC showed that both NAG and alpha 1M values at day 7 had moderate discriminative sensitivity for predicting severe AKI (NAG : 0.783, 95 % confidence interval [CI] 0.611-0.966 ; and alpha 1M: 0.807, 95 % CI 0.647-0.956, respectively). Multivariate logistic regression showed that only alpha 1M at day 7 was significantly associated with the occurrence of severe AKI(odds ratio 18.4, 95 % CI 1.210-736, p=0.035)., Conclusion: Consecutive monitoring of urinary alpha 1M after SCT is likely to be useful for early identification of patients at risk for severe AKI, leading to early death.

A 63-year-old woman, without a family history of hemophilia, was admitted to our hospital because of subcutaneous bleeding, intramuscular and intra-articular hematoma, and macroscopic hematuria. On routine blood analysis, a prolonged activated partial thromboplastin time, decreased concentration of factor VIII to less than 1%, and a markedly elevated level of factor VIII inhibitor to 14.1 BU/ml were revealed. Diagnosis of acquired hemophilia was made and she was treated with prednisolone and recombinant activated factor VII (rFVIIa). On day 9 of rFVIIa therapy, she was complicated by acute renal failure (ARF) with increasing macroscopic hematuria. Computed tomography revealed bilateral swelling of the kidneys with bleeding and dilatation of the left renal pelvis. Activated prothrombin complex concentrates (aPCC) was administrated in combination with steroid pulse therapy and hydration. The bleeding tendency, including ARF, was improved with aPCC, and she was treated with prednisolone and cyclophosphamide. She is currently in good health and attending an outpatients' clinic. Acquired hemophilia is associated with various underlying conditions, but our patient did not show any previous history. ARF is a rare complication in acquired hemophilia, requiring a non-invasive treatment combination with early induction of immunosuppressive therapy.

We review diagnostic importance of neutrophil gelatinase-associated lipocalin (Ngal or lipocalin 2) in acute kidney injury and chronic kidney disease, and discuss the impact of novel biomarker analysis upon progress of nephrology.

Acute renal failure (ARF) is an acute loss of kidney function that occurs over days to weeks and results in an inability to appropriately excrete nitrogenous wastes and creatinine (Cre). ARF is diagnosed by elevations of blood urea nitrogen and serum Cre level, which is classified as prerenal, intrinsic and postrenal according to their mechanisms. However, discriminate diagnosis of these types by blood biochemistry findings is difficult. Recently, cystatin C (Cys-C), a basic protein having isoelectric point 9.3 with a molecular weight of 13.3 kDa, is freely filtered at the level of the glomerulus and virtually all is reabsorbed and metabolized by the proximal tubular cells. Therefore, assuming constant cellular production, serum Cys-C level has the potential to be an excellent surrogate marker of glomerular filtration rate. Because Cre is electrically charged neutrally, there is a possibility that the permeation of Cys-C, which is positively charged, is diffluent from that of Cre through glomerular basement membrane due to the type of the renal failure. We determined blood concentrations of Cys-C and Cre in a patients with prerenal renal failure (17 patients), intrinsic renal failure (232 patients) and postrenal renal failure (13 patients) as compared with healthy subjects (n = 771). We found that patients with postrenal renal failure displayed significantly elevated Cre/Cys-C ratio (mean +/- standard deviation) (8.3 +/- 8.0, p < 0.001) as compared with healthy subjects (1.1 +/- 0.2), prerenal (0.6 +/- 0.2) and intrinsic (1.6 +/- 0.5). These findings suggest that measurement of Cys-C concentration and Cre/Cys-C ratio may be useful for the discriminate diagnosis of postrenal renal failure.

A 60-year-old man, who had been diagnosed as having paroxysmal nocturnal hemoglobinuria(PNH) in 1994, was admitted to our hospital with general fatigue, and dark urine after a common-cold in January 2001. In the peripheral blood, the red blood cell count was 136 x 10(4)/microl, hemoglobin 4.0 g/dl and hematocrit 12.4%. The serum creatinine level was 9.9 mg/dl. Kidney biopsy revealed focal and segmental proliferation of mesangial cells, mesangial matrix expansion, acute tubular necrosis, interstitial fibrosis and hemosiderine deposits in the tubular epithelial cells confirmed by Berlin-blue staining. Immunofluorescence microscopy showed IgA and C3 deposition in the mesangium. Electron microscopy revealed electron dense deposits in the mesangial area and heavy electron-dense hemosiderin pigments in proximal tubular epithelial cells. After the transfusion of six units of washed red blood cells and two sessions of hemodialysis, the renal function returned to the levels before admission.