Abstract Background Cardiovascular disease among hemodialysis (HD) patients is linked to poor outcomes. The Acute Dialysis Quality Initiative Workgroup proposed echocardiographic (ECHO) criteria for ...structural heart disease (SHD) in dialysis patients. The association of SHD with important patient outcomes is not well defined. Objectives This study sought to determine prevalence of ECHO-determined SHD and its association with survival among incident HD patients. Methods We analyzed patients who began chronic HD from 2001 to 2013 who underwent ECHO ≤1 month prior to or ≤3 months following initiation of HD (n = 654). Results Mean patient age was 66 ± 16 years, and 60% of patients were male. ECHO findings that met 1 or more and ≥3 of the new criteria were discovered in 87% and 54% of patients, respectively. Over a median of 2.4 years, 415 patients died: 108 (26%) died within 6 months. Five-year mortality was 62%. Age- and sex-adjusted structural heart disease variables associated with death were left ventricular ejection fraction (LVEF) ≤45% (hazard ratio HR: 1.48; confidence interval CI: 1.20 to 1.83) and right ventricular (RV) systolic dysfunction (HR: 1.68; CI: 1.35 to 2.07). An additive of higher death risk included LVEF ≤45% and RV systolic dysfunction rather than neither (HR: 2.04; CI: 1.57 to 2.67; p = 0.53 for test for interaction). Following adjustment for age, sex, race, diabetic kidney disease, and dialysis access, RV dysfunction was independently associated with death (HR: 1.66; CI 1.34 to 2.06; p < 0.001). Conclusions SHD was common in our HD study population, and RV systolic dysfunction independently predicted mortality.
Background Recent policy clarifications by the Centers for Medicare & Medicaid Services have changed access to outpatient dialysis care at end-stage renal disease (ESRD) facilities for individuals ...with acute kidney injury in the United States. Tools to predict “ESRD” and “acute” status in terms of kidney function recovery among patients who previously initiated dialysis therapy in the hospital could help inform patient management decisions. Study Design Historical cohort study. Setting & Participants Incident hemodialysis patients in the Mayo Clinic Health System who initiated in-hospital renal replacement therapy (RRT) and continued outpatient dialysis following hospital dismissal (2006 through 2009). Predictor Baseline estimated glomerular filtration rate (eGFR), acute tubular necrosis from sepsis or surgery, heart failure, intensive care unit, and dialysis access. Outcomes Kidney function recovery defined as sufficient kidney function for outpatient hemodialysis therapy discontinuation. Results Cohort consisted of 281 patients with a mean age of 64 years, 63% men, 45% with heart failure, and baseline eGFR ≥ 30 mL/min/1.73 m2 in 46%. During a median of 8 months, 52 (19%) recovered, most (94%) within 6 months. Higher baseline eGFR (HR per 10–mL/min/1.73 m2 increase eGFR, 1.27; 95% CI, 1.16-1.39; P < 0.001), acute tubular necrosis from sepsis or surgery (HR, 3.34; 95% CI, 1.83-6.24; P < 0.001), and heart failure (HR, 0.40; 95% CI, 0.19-0.78, P = 0.007) were independent predictors of recovery within 6 months, whereas first RRT in the intensive care unit and catheter dialysis access were not. There was a positive interaction between absence of heart failure and eGFR ≥ 30 mL/min/1.73 m2 for predicting kidney function recovery ( P < 0.001). Limitations Sample size. Conclusions Kidney function recovery in the outpatient hemodialysis unit following in-hospital RRT initiation is not rare. As expected, higher baseline eGFR is an important determinant of recovery. However, patients with heart failure are less likely to recover even with a higher baseline eGFR. Consideration of these factors at hospital discharge informs decisions on ESRD status designation and long-term hemodialysis care.
We present the case of a 62-year-old man with a history of Wegener granulomatosis who developed chronic thrombotic microangiopathy attributed to gemcitabine chemotherapy. Wegener granulomatosis had ...been diagnosed 15 years earlier, and the patient was treated using cyclophosphamide and prednisone, then maintained on mycophenolate mofetil and prednisone. Four years previously, he had been treated with mitomycin C for urothelial carcinoma and at the time of presentation had developed significant anemia and thrombocytopenia after a course of gemcitabine and carboplatin due to metastasis of the carcinoma. He was managed using red blood cell and platelet transfusions but then developed acute kidney injury, along with progressive dyspnea and pulmonary infiltrates. Imaging studies showed bilateral ureteral obstruction requiring placement of nephrostomy tubes. Because of concern about a flare of Wegener granulomatosis after withdrawing maintenance immunosuppression in the context of the malignancy, a kidney biopsy was performed that showed chronic thrombotic microangiopathy, likely secondary to gemcitabine chemotherapy. Clinical, laboratory, and pathologic findings of this case are discussed to illustrate the natural history of thrombotic microangiopathy associated with gemcitabine chemotherapy.
A 68-year-old woman with a history of hepatitis C (contracted from a blood transfusion in 1974) complicated by cirrhosis and portal hypertension came to the Mayo Clinic in Rochester, Minn, for ...evaluation for possible liver transplantation. Her symptomatic ascites had been treated initially with furosemide and spironolactone, but this treatment regimen was limited because of an increase in her creatinine level. During evaluation, hypertension (an average blood pressure of 180/90 mm Hg on 6-hour ambulatory monitoring) and abnormal renal function were noted. She was referred to our institution for further evaluation of her blood pressure and abnormal urinalysis results.
Up-regulation of heme oxygenase-1 (HO-1) occurs in, and often confers protection to, the injured kidney. Up-regulation of monocyte chemoattractant protein-1 (MCP-1) promotes not only acute and ...chronic nephritides but also acute ischemic and nephrotoxic injury. The present study was stimulated by the hypothesis that expression of MCP-1 is suppressed by HO-1, and analyzed the effect of HO-1 on the expression of MCP-1 in stressed and unstressed conditions.
Expression of MCP-1 and pathophysiologic correlates were examined in HO-1 knockout (HO-1-/-) and wild-type (HO-1+/+) mice in the unstressed state in young and aged mice, and following nephrotoxic and ischemic insults.
In unstressed HO-1-/- mice, plasma levels of MCP-1 protein were elevated, and MCP-1 mRNA expression was increased in circulating leukocytes and in the kidney. Such early and heightened up-regulation of MCP-1 was eventually accompanied by phenotypic changes in the aged kidney consistent with MCP-1, namely, proliferative changes in glomeruli, tubulointerstitial disease, and up-regulation of transforming growth factor-beta1 (TGF-beta1) and collagens I, III, and IV. In response to a nephrotoxic insult such as hemoglobin, MCP-1 mRNA was up-regulated in a markedly sustained manner in HO-1-/- mice. In response to a duration of ischemia that exerted little effect in HO-1+/+ mice, HO-1-/- mice exhibited higher expression of MCP-1 mRNA, enhanced activation of nuclear factor-kappaB (NF-kappaB) (the transcription factor that regulates MCP-1), markedly greater functional and structural renal injury, increased caspase-3 expression, and increased mortality.
In the absence of HO-1, expression of MCP-1 is significantly and consistently enhanced in unstressed and stressed conditions. We speculate that the protective effects of HO-1 in injured tissue may involve, at least in part, the capacity of HO-1 to restrain up-regulation of MCP-1.
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