Although hyperuricemia has been shown to be associated with the progression of cardiovascular disorder and chronic kidney disease (CKD), there is conflicting evidence as to whether xanthine oxidase (XO) inhibitors confer organ protection besides lowering serum urate levels. In this study, we addressed the cardio-renal effects of XO inhibition in rodent CKD model with hyperuricemia. Sprague-Dawley rats underwent 5/6 nephrectomy and received a uricase inhibitor oxonic acid for 8 weeks (RK + HUA rats). In some rats, a XO inhibitor febuxostat was administered orally. Compared with control group, RK + HUA group showed a significant increase in albuminuria and renal injury. Febuxostat reduced serum uric acid as well as urinary albumin levels. Histological and immunohistochemical analysis of the kidney revealed that febuxostat alleviated glomerular, tubulointerstitial, and arteriolar injury in RK + HUA rats. Moreover, in the heart, RK + HUA showed individual myofiber hypertrophy and cardiac fibrosis, which was significantly attenuated by febuxostat. We found that renal injury and the indices of cardiac changes were well correlated, confirming the cardio-renal interaction in this model. Finally, NF-E2-related factor 2 (Nrf2) and the downstream target heme oxygenase-1 (HO-1) protein levels were increased both in the heart and in the kidney in RK + HUA rats, and these changes were alleviated by febuxostat, suggesting that tissue oxidative stress burden was attenuated by the treatment. These data demonstrate that febuxostat protects against cardiac and renal injury in RK + HUA rats, and underscore the pathological importance of XO in the cardio-renal interaction.
Background: Rhabdomyolysis may develop into acute kidney injury (AKI), a life-threatening complication. Obese people are at risk for rhabdomyolysis due to prolonged immobilization. However, there are only a few reports of rhabdomyolysis-induced AKI due to prolonged immobilization after falls in morbidly obese people. Myoglobin is a causative compound for rhabdomyolysis-induced AKI, but the lack of treatments targeting its mechanism is a problem. Case presentation: Two morbidly obese women (body mass index > 40.0 kg/m 2) who fell on the floor at home and remained in the same posture for more than 12 h developed rhabdomyolysis-induced AKI. Both patients received aggressive fluid resuscitation but required hemodialysis because of persistent oliguria. They underwent 11 and 2 intermittent hemodialysis (HD) sessions with a conventional polymethylmethacrylate (PMMA) high-flux dialyzer, respectively, and their renal functions returned to baseline after withdrawal of HD. Conclusions: We should be aware that morbidly obese people are at risk for rhabdomyolysis-induced AKI due to prolonged immobilization, such as after falls. At present, prophylactic renal replacement therapy (RRT) is not recommended for rhabdomyolysis. We need to reevaluate whether RRT using the appropriate membranes to effectively remove myoglobin including the PMMA membrane can improve the renal outcome in patients with rhabdomyolysis-induced AKI.
The patient was a 38-year-old man who had experienced nausea and fever for a few days and presented with back pain, oliguria, and pyuria, suggesting acute pyelonephritis (APN). He showed acute kidney injury (AKI) with bilateral kidney enlargement and was using nonsteroidal anti-inflammatory drugs (NSAIDs). AKI-induced by APN was confirmed by kidney biopsy. The AKI was successfully treated with antibiotic therapy. A search of the relevant literature for reports on histopathologically-proven APN-induced severe AKI revealed that the key characteristics were bilateral kidney enlargement with pyuria without casts. Oligoanuria was frequently associated with APN-induced severe AKI, and NSAID use may be a possible risk factor. Prompt antibiotic treatment based on the clinical characteristics of APN-induced AKI can improve the renal outcome.
A 39-year-old man presented with peripheral eosinophilia, pulmonary eosinophilic infiltrate, and renal failure due to acute tubulointerstitial nephritis (TIN). He had experienced childhood asthma and was negative for anti-neutrophil cytoplasmic antibody (ANCA). He was tentatively diagnosed with ANCA-negative eosinophilic granulomatous polyangiitis (EGPA) or idiopathic hypereosinophilic syndrome (HES). Renal involvement of isolated TIN with eosinophil infiltration is rare in EGPA and HES and does not seem to have a good prognosis in the literature. However, his condition improved well with corticosteroids and mepolizumab. The revised classification of EGPA based on the etiology should dictate the proper treatment in suspected EGPA patients with nonsystemic vasculitis.
Rationale:
T-cell acute lymphoblastic leukemia is a relatively uncommon disorder in adults. Kidneys are not frequently invaded by leukemic cells, and patients with adult ALL showing nephromegaly as an initial presentation are rare.
Patient concerns:
A 54-year-old man was referred to our institution for mild anemia and thrombocytopenia. Laboratory tests showed bicytopenia with abnormal lymphoid cells in the peripheral blood and mild renal dysfunction.
Diagnosis:
Ultrasonography and computed tomography (CT) revealed bilateral enlargement of the kidneys. [18F]-fluorodeoxyglucose positron emission tomography/CT demonstrated a strong increase in metabolic uptake in the bilateral kidneys. A kidney biopsy revealed a leukemia invasion into the parenchyma. Based on the lymphocytic repertoire, the patient's condition was diagnosed as T-cell acute lymphoblastic leukaemia.
Interventions:
The patient received hyper-cyclophosphamide, vincristine, adriamycin, and dexamethasone and high-dose methotrexate and cytarabine as induction chemotherapy. After his leukemia relapsed, he received nelarabine as a second induction therapy and underwent haploidentical peripheral blood stem cell transplantation.
Outcomes:
Complete remission (CR) was achieved after chemotherapy. Chemotherapy also improved renal function associated with the normalization of bilateral nephromegaly. Repeated [18F]-fluorodeoxyglucose - positron emission tomography/CT posttreatment showedregression of metabolic uptake in the bilateral kidneys. The patient underwent cord blood transplantation at the first CR, but his leukemia relapsed 9 months later. At relapse, bilateral nephromegaly reappeared. Then, the second induction therapy induced CR for at least 10 months after induction therapy.
Lessons:
Although rare, ALL in the initial and relapsed phases can be associated with bilateral nephromegaly and renal impairment due to the invasion of leukemic cells into the parenchyma with or without abnormal leukemic cells in circulation. Leukemia is an important differential diagnosis of renal impairment with bilateral nephromegaly.
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