Urea reduction ratio may be a simpler approach for measurement of adequacy of intermittent hemodialysis in acute kidney injury.

BACKGROUND: Assessment of adequacy of intermittent hemodialysis (IHD) is conventionally based upon urea kinetic models for calculation of single pool Kt/Vurea (Kt/V), with 1.2 accepted as minimum adequate clearance for thrice weekly IHD. In the Acute Renal Failure Trial Network (ATN) Study, adequacy of IHD in patients with acute kidney injury (AKI) was assessed using Kt/V. However, equations for Kt/V require volume of distribution of urea, which is highly variable in AKI. Therefore, simpler methods are needed to assess adequacy of IHD in AKI. We assessed correlation of urea reduction ratio (URR) with Kt/V and determined URR thresholds corresponding to Kt/V values to determine if URR could be a simpler means to assess the delivered dose of IHD. METHODS: Using patients who received IHD for 2.5-6 h and with pre-dialysis BUN ≥20 mg/dL, we plotted URR against Kt/V. We determined URR thresholds (0.60 to 0.75) corresponding to Kt/V ≥ 1.2, 1.3, and 1.4. We generated receiver operating characteristic (ROC) curves for increasing URR values for each level of Kt/V to identify the corresponding thresholds of URR. RESULTS: There was strong correlation between URR and Kt/V. ROC curves comparing URR with Kt/V ≥ 1.2, 1.3, and 1.4 had area under the curves (AUC) of 0.99. Sensitivity and specificity of URR ≥0.67 for corresponding values of Kt/V ≥ 1.2 were 0.769 (95% CI: 0.745 to 0.793) and 0.999 (95% CI: 0.997 to 1.000), respectively and the sensitivity and specificity of URR ≥0.67 for corresponding values of Kt/V ≥ 1.4 were 0.998 (95% CI: 0.995 to 1.000) and 0.791 (95% CI: 0.771 to 0.811), respectively. CONCLUSIONS: Targeting a URR ≥0.67 provides a simplified means of assessing adequacy of IHD in patients with AKI. Use of URR will enhance ability to assess delivery of small solute clearance and improve adherence with clinical practice guidelines in AKI.

Triple confusion: An interesting case of proteinuria in pregnancy.

Pregnancy-related renal diseases are unique and need special attention, both for diagnosis and management. The major confounding factors for diagnosis are the physiological multiorgan changes that occur throughout the gestational period. Proper diagnosis of the renal disease is also important, given the impact of varied management options both on the maternal and fetal health. A young middle-aged female with a long-standing history of diabetes presented to the hospital with worsening proteinuria in her second trimester of pregnancy. Clinical history, examinations, and laboratory analysis did not give any clues for diagnosis of a specific disease entity. This led us to take the risk of renal biopsy for a tissue diagnosis. The odds of renal biopsy favored the management decision in her case, thereby avoiding the confusions prior to biopsy. The pathological diagnosis is a surprise though not a unique entity on its own (minimal change disease in pregnancy). The case illustrates the disparity of clinical presentations and the pathology in patients, and the importance of renal biopsy in pregnant patients in particular.

Modality of RRT and Recovery of Kidney Function after AKI in Patients Surviving to Hospital Discharge.

BACKGROUND AND OBJECTIVES: Observational evidence has suggested that RRT modality may affect recovery after AKI. It is unclear whether initial choice of intermittent hemodialysis or continuous RRT affects renal recovery, survival, or development of ESRD in critically ill patients when modality choice is made primarily on hemodynamics. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We performed a retrospective cohort study examining adults (≥18 years old) admitted to intensive care units from 2000 to 2008 who received RRT for AKI and survived to hospital discharge or 90 days. We analyzed renal recovery (alive and not requiring RRT) and reasons for nonrecovery (death or ESRD) at 90 and 365 days. Conditional multivariable logistic regression was used to assess differences in renal recovery at 90 and 365 days between continuous RRT and intermittent hemodialysis. Models were stratified by propensity for continuous RRT and adjusted for age and reference creatinine. RESULTS: Of 4738 patients with Kidney Disease Improving Global Outcomes stage 3 AKI, 1338 (28.2%) received RRT, and 638 (47.7%) survived to hospital discharge (353 intermittent hemodialysis and 285 continuous RRT). Recovery from AKI was lower for intermittent hemodialysis versus continuous RRT at 90 days (66.6% intermittent hemodialysis versus 75.4% continuous RRT; P=0.02) but similar at 365 days (54.1% intermittent hemodialysis versus 59.6% continuous RRT; P=0.17). In multivariable analysis, there was no difference in odds of recovery at 90 or 365 days for patients initially treated with continuous RRT versus intermittent hemodialysis (90 days: odds ratio, 1.19; 95% confidence interval, 0.91 to 1.55; P=0.20; 365 days: odds ratio, 0.93; 95% confidence interval, 0.72 to 1.2; P=0.55). CONCLUSIONS: We found no significant difference in hazards for nonrecovery or reasons for nonrecovery (mortality or ESRD) with intermittent hemodialysis versus continuous RRT. These results suggest that, when initial RRT modality is chosen primarily on hemodynamics, renal recovery and clinical outcomes in survivors are similar between intermittent hemodialysis and continuous RRT.

Membranous nephropathy: a rare renal manifestation of IgG4-related systemic disease.

This is a case of IgG4-related systemic disease (ISD) and its rare renal manifestation as membranous nephropathy (MGN). The patient presented with peripheral edema, hematuria and proteinuria. 24-h urine revealed proteinuria of up to 15 g/d. Renal biopsy revealed MGN and many IgG4-positive plasma cells. Serum IgG4 levels were elevated at 750 mg/dl (9 - 89 mg/d). Biopsies of multiple tissues revealed many IgG4-positive plasma cells. Prednisone was initiated after making the diagnosis of ISD. However, the patient progressed into renal failure and eventually needed dialysis despite rituximab therapy. The renal manifestation of ISD typically shows tubulointerstitial nephritis, but, rarely, it may include glomerular abnormalities such as MGN or membranoproliferative glomerulonephritis. Castleman disease (CD) and ISD share similarities in pathology, particularly in the lymph nodes. Rituximab has shown promising results in some patients with ISD, CD, and MGN, and its use should be considered in steroid-resistant cases. Clinicians need to be made aware of ISD and its varied presentations. Timely initiation of steroid therapy can induce remission, and delay in therapy can cause permanent organ damage. Therefore, clinicians must have a high index of suspicion to make an early diagnosis of ISD in order to initiate appropriate treatment.

Peripheral vascular disease severity impacts health outcomes and health-related quality of life in maintenance hemodialysis patients in the HEMO Study.

BACKGROUND: In patients with end-stage renal disease, peripheral vascular disease (PVD) is prevalent. We assessed the extent to which severity of PVD predicts mortality, hospitalizations and health-related quality of life (HRQOL) in hemodialysis (HD) patients enrolled in the Hemodialysis (HEMO) Study. METHODS: We performed a subanalysis of the HEMO Study, a randomized controlled trial. Adjusted predictors of PVD were analyzed through a multivariable stepwise ordinal logistic model. Relationships between PVD severity and mortality and hospitalizations were determined with Cox proportional hazards models. Relationships between PVD severity and HRQOL were modeled via linear regression and generalized estimating equations. RESULTS: Older age, diabetes, non-African-American race, ischemic heart disease, cerebrovascular disease and longer transplant wait time were associated with more severe PVD. Patients with severe PVD were more likely to suffer from all-cause mortality [hazard ratio (HR) 1.77, 95% confidence interval 1.30-2.40, P<0.001], cardiac death [HR 1.89 (95% confidence interval 1.15-3.11), P=0.001] and infectious death [HR 1.75 (95% confidence interval 1.30-2.34), P<0.001]. Increasing PVD severity was also associated with first cardiac hospitalization or all-cause mortality (P=0.05) and first cardiac hospitalization or cardiac death (P=0.03). HRQOL scores were lower for patients with increasingly severe PVD. CONCLUSIONS: These findings underscore the burden of clinically symptomatic PVD in HD patients and its impact on morbidity and mortality. Whether early detection of PVD and prompt initiation of therapy to prevent its progression in the HD population would improve HRQOL and survival outcomes remain to be proven.

Heart failure severity scoring system and medical- and health-related quality-of-life outcomes: the HEMO study.

BACKGROUND: Cardiac disease is the leading cause of death in US prevalent hemodialysis (HD) patients. There is a lack of data about the impact of the severity of heart failure (HF) on outcomes and health-related quality of life (HRQoL) in HD patients. We aimed to determine the prognostic importance of the Index of Disease Severity (IDS) of the Index of Coexistent Disease (ICED) scoring system as an HF severity measure. STUDY DESIGN: Subanalysis of the Hemodialysis (HEMO) Study, a randomized controlled trial. Relationships between HF severity and mortality and cardiac hospitalizations were determined using Cox proportional hazards models. The relationship between HF severity and HRQoL scores was modeled using linear regression and generalized estimating equations. SETTING & PARTICIPANTS: 1,846 long-term HD patients at 15 clinical centers including 72 dialysis units. PREDICTOR OR FACTOR: HF severity classified using the IDS of the ICED scoring system. OUTCOMES: Mortality (all cause and cause specific), cardiac hospitalizations, and HRQoL. MEASUREMENTS: All-cause, cardiac, and infectious deaths; cardiac hospitalizations; and HRQoL scores from the Kidney Disease Quality of Life-Long Form. RESULTS: HF was present in 40% of HD patients. Increasing severity of HF was associated with older age, greater likelihood of diabetes, and lower serum albumin level (all P < 0.001). Adjusted HRs for all-cause mortality were 1.31 (95% CI, 1.12-1.53), 1.48 (95% CI, 1.19-1.85), and 2.11 (95% CI, 1.43-3.11) for mild, moderate, and severe HF, respectively (P < 0.001). All-cause, cardiac, and infectious mortality and cardiac hospitalizations increased with increasing severity of HF. Increasing HF severity was associated with decreases in HRQoL, particularly in physical functioning and sleep quality. LIMITATIONS: This study is limited by the small sample size in the most severe HF group. CONCLUSIONS: Increasing severity of HF is associated with increased mortality and cardiac hospitalizations and worse HRQoL, especially in perceived physical limitations. These findings emphasize the utility of the IDS of the ICED score as a valid prognostic tool for medical and HRQoL outcomes in the HD population with HF.

Risk factors for CKD in persons with kidney stones: a case-control study in Olmsted County, Minnesota.

BACKGROUND: Kidney stones are associated with increased risk of chronic kidney disease (CKD); however, risk factors in the general community are poorly defined. STUDY DESIGN: A nested case-control study was performed in residents of Olmsted County, MN, who presented with a kidney stone at the Mayo Clinic in 1980-1994 to contrast patients with kidney stones who developed CKD with a group that did not. SETTING & PARTICIPANTS: Participants were selected from the Rochester Epidemiology Project, an electronic linkage system among health care providers in Olmsted County, MN. Cases were identified by diagnostic code for CKD and confirmed to have an estimated glomerular filtration rate < 60 mL/min/1.73 m(2). Controls were matched 2:1 to cases for age, sex, date of first kidney stone, and length of medical record. PREDICTOR: Charts were abstracted to characterize stone disease, hypertension, diabetes, obesity, tobacco use, ileal conduit, symptomatic stones, type and number of stones, urinary tract infections, number and type of surgical procedures, and medical therapy. OUTCOMES & MEASUREMENTS: Kidney stone patients with CKD were compared with matched stone patients without CKD. RESULTS: There were 53 cases and 106 controls with a mean age of 57 years at first stone event and 59% men. In kidney stone patients, cases with CKD were significantly more likely (P < 0.05) than controls to have had a history of diabetes (41.5% vs 17.0%), hypertension (71.7% vs 49.1%), frequent urinary tract infections (22.6% vs 6.6%), struvite stones (7.5% vs 0%), and allopurinol use (32.1% vs 4.7%) based on univariate analysis. LIMITATIONS: Potential limitations include limited statistical power to detect associations, incomplete data from 24-hour urine studies, and that stone composition was not always available. CONCLUSION: As in the general population, hypertension and diabetes are associated with increased risk of CKD in patients with kidney stones. However, other unique predictors were identified in patients with kidney stones that increased the possibility of CKD. Further studies are warranted to elucidate the nature of these associations.

Exploratory study of relationship between hospitalized heart failure patients and chronic renal replacement therapy.

BACKGROUND: Chronic kidney disease (CKD) is common in heart failure (HF) and is associated with poor outcomes. Renal replacement therapy (RRT) may be deferred over concerns regarding tolerability and outcomes in HF. Our objectives were to ascertain the incidence of RRT, changes in RRT incidence over time and the association between RRT and survival in hospitalized HF patients. METHODS: A retrospective cohort study of consecutive hospitalized HF patients was performed at a single centre from 1987 to 2002 with RRT data from the United States Renal Data System. RESULTS: Of 6276 HF patients without RRT on admission, 304 commenced chronic (>or=3 months) RRT (280 dialysis only; 24 transplant) at a median of 475 days after dismissal. Overall incidence was 1.6% per year. Risk-adjusted incidence increased over time and was similar in those with preserved or reduced (<50%) ejection fraction. RRT patients were younger but had worse renal function and anaemia, and more diabetes, hypertension and coronary disease. Unadjusted survival was worse in the RRT group. However, risk-adjusted survival was similar in RRT and non-RRT groups (HR = 1.11, 95% CI 0.94-1.29, P > 0.05). CONCLUSIONS: Our data show that although RRT is increasingly used in HF patients, the impact on risk-adjusted mortality remains to be established. Further studies should focus on defining the appropriate clinical settings in which RRT should be used in HF, the timing and type of RRT and whether RRT can improve specific outcomes.

Acute decompensated heart failure and the cardiorenal syndrome.

Heart failure is one of the leading causes of hospitalizations in the United States. Concomitant and significant renal dysfunction is common in patients with heart failure. Increasingly, the syndrome of heart failure is one of cardiorenal failure, in which concomitant cardiac and renal dysfunctions exist, with each accelerating the progression of the other. One fourth of patients hospitalized for the treatment of acute decompensated heart failure will experience significant worsening of renal function, which is associated with worse outcomes. It remains unclear whether worsening renal function specifically contributes to poor outcomes or whether it is merely a marker of advanced cardiac and renal dysfunction. Diuretic resistance, with or without worsening renal function, is also common in acute decompensated heart failure, although the definition of diuretic resistance, its prevalence, and prognostic implications are less well defined. The term cardiorenal syndrome has been variably associated with cardiorenal failure, worsening renal function, and diuretic resistance but is more comprehensively defined as a state of advanced cardiorenal dysregulation manifest by one or all of these specific features. The pathophysiology of the cardiorenal syndrome is poorly understood and likely involves interrelated hemodynamic and neurohormonal mechanisms. When conventional therapy for acute decompensated heart failure fails, mechanical fluid removal via ultrafiltration, hemofiltration, or hemodialysis may be needed for refractory volume overload. While ultrafiltration can address diuretic resistance, whether ultrafiltration prevents worsening renal function or improves outcomes in patients with cardiorenal syndrome remains unclear. Evidence regarding the potential renal-preserving effects of nesiritide is mixed, and further studies on the efficacy and safety of different doses of nesiritide in heart failure therapy are warranted. Newer therapeutic agents, including vasopressin antagonists and adenosine antagonists, hold promise for the future, and clinical trials of these agents are underway.

Nodular glomerulosclerosis: renal lesions in chronic smokers mimic chronic thrombotic microangiopathy and hypertensive lesions.

Cigarette smoking is associated with vascular lesions and chronic renal failure. In this report, we describe clinical and kidney biopsy findings for a 66-year-old woman with a history of long-term heavy cigarette smoking who developed proteinuria and decreasing renal function. This study also describes clinical and kidney biopsy findings for 9 patients with a history of smoking. None of these patients had hypertension, diabetes mellitus, or other risk factors that might result in vascular injury. Renal biopsy specimens showed a range of long-term changes with varying degrees of focal segmental or focal global glomerulosclerosis, nodular glomerulosclerosis, ischemic glomeruli, interstitial fibrosis and tubular atrophy, and mild to moderate arterial sclerosis and arteriolar hyalinosis. Electron microscopy often showed glomerular capillary wall thickening caused by subendothelial expansion by cellular elements and new basement formation resulting in segments of double contours. These changes indicate endothelial injury and glomerular capillary wall remodeling; the lesions mimic those seen in patients with chronic hypertension and chronic or healed thrombotic microangiopathies.

Use of a novel ultrafiltration device as a treatment strategy for diuretic resistant, refractory heart failure: initial clinical experience in a single center.

BACKGROUND: The System 100 UF device allows ultrafiltration (UF) via peripheral access and is approved for use in heart failure (HF), although clinical trials defining optimal target population and clinical utility are lacking. We report our initial experience with clinical use of this system in very advanced, diuretic resistant HF patients. METHODS AND RESULTS: Eleven HF patients (mean age 70 years) underwent 1 to 5 UF treatments each (total 32 UF). The goal was to remove 4 liters of fluid per 8-hour UF. Baseline creatinine averaged 2.2 mg/dL (range .9-3.2) while estimated glomerular filtration rates (GFRs) averaged 38 mL/min (range 20-87). Nine patients (82%) had moderate (GFR 30-59; n = 3) or severe (GFR <30; n = 6) renal dysfunction. Nine patients (82%) had documented right ventricular dysfunction, 6 with severe tricuspid regurgitation. Average daily intravenous furosemide dose prior to UF was 258 mg (range 80-480). Patients had received nesiritide (n = 4), dopamine (n = 4), and zaroxylyn (n = 7) prior to UF. Of the 32 UF treatments, 13 (41%) removed >3500 mL, 11 (34%) removed 2500-3500 mL, and 8 (25%) removed <2500 mL. Only one UF treatment (3%) was aborted due to hypotension. There were no significant complications related to UF. Five patients (45%) experienced an increase in creatinine of >.3 mg/dl. Five patients required dialysis for persistent diuretic resistant volume overload or uremic symptoms. Six-month mortality was 55%. CONCLUSIONS: Peripheral UF safely but variably removed fluid. In this very high-risk, advanced HF population, 45% of patients developed worsening renal function during UF therapy. Controlled studies are needed to determine the impact of UF on renal function and outcomes in high-risk populations such as this.

Metastatic malignant melanoma of the gastrointestinal tract.

Malignant melanoma is one of the most common malignancies to metastasize to the gastrointestinal (GI) tract. Metastases to the GI tract can present at the time of primary diagnosis or decades later as the first sign of recurrence. Symptoms may include abdominal pain, dysphagia, small bowel obstruction, hematemesis, and melena. We report 2 cases of malignant melanoma metastatic to the GI tract, followed by a review of the literature. The first case is a 72-year-old man who underwent resection of superficial spreading melanoma on his back 13 years previously who presented with dysphagia. A biopsy specimen of a mucosal fold in a gastric fundus noted during endoscopy was taken and revealed metastatic malignant melanoma, which was resected 1 month later. Three weeks later, the patient was found to have an ulcerated jejunal metastatic melanoma mass, which was also resected. The second case is a 63-year-old man with an ocular melanoma involving the chorold of the left eye that had been diagnosed 4 years previously, which had been excised several times, who presented with anorexia, dizziness, and fatigue. He was found to have cerebellar and stomach metastases. He underwent adjuvant radiation therapy, chemotherapy, and surgical resection of the gastric melanoma metastasis. In patients with a history of melanoma, a high index of suspicion for metastasis must be maintained if they present with seemingly unrelated symptoms. Diagnosis requires careful inspection of the mucosa for metastatic lesions and biopsy with special immunohistochemical stains. Management may include surgical resection, chemotherapy, immunotherapy, observation, or enrollment in clinical trials. Prognosis is poor, with a median survival of 4 to 6 months.

Incidence of noncardiac vascular disease in rheumatoid arthritis and relationship to extraarticular disease manifestations.

OBJECTIVE: To investigate the incidence of noncardiac vascular disease in patients with rheumatoid arthritis (RA) and its relationship to systemic extraarticular disease in a community-based cohort. METHODS: A retrospective medical record review of 609 patients with incident RA diagnosed during 1955-1994 was carried out in Olmsted County, Minnesota. Patients were followed up from 1955 to 2000 (median followup 11.8 years). Incident noncardiac vascular disease and severe extraarticular RA manifestations (including pericarditis, pleuritis, and vasculitis) were recorded according to predefined criteria, and incidence rates were estimated. Using Cox proportional hazards models, the risk (hazard ratio [HR]) of developing vascular events was assessed in patients with and without severe extraarticular RA. RESULTS: Cerebrovascular and peripheral arterial events occurred in 139 patients (22.8%). The 30-year cumulative incidence rates of peripheral arterial events, cerebrovascular events, and venous thromboembolic events were estimated to be 19.6%, 21.6%, and 7.2%, respectively. The presence of severe extraarticular RA manifestations was found to be associated with all subgroups of noncardiac vascular disease except cerebrovascular disease alone (HR 2.3, 95% confidence interval [95% CI] 1.2-4.3 for peripheral arterial events; HR 3.7, 95% CI 1.3-10.3 for venous thromboembolic events; HR 1.5, 95% CI 0.7-3.2 for cerebrovascular events) after adjusting for age, sex, body mass index, smoking, and rheumatoid factor status. CONCLUSION: This is the first study to assess the incidence of noncardiac vascular disease in RA. Severe extraarticular RA was associated with all forms of noncardiac vascular disease except cerebrovascular disease alone. Similar to cardiac disease, the excess risk of noncardiac vascular disease in RA is likely to be related, in part, to the systemic inflammation associated with the extraarticular manifestations of RA.

Lactobacillus gasseri causing Fournier's gangrene.

Fournier's gangrene is characterized as an aggressive necrotizing process caused by a polymicrobial infection that includes virulent organisms. We report the first case of Fournier's gangrene caused by a low-virulence organism, Lactobacillus gasseri.

Histoplasmosis with tenosynovitis of the hand and hypercalcemia mimicking sarcoidosis.

We report on an otherwise healthy 47-year-old male who developed subacute tenosynovitis of the hand associated with night sweats and inguinal lymphadenopathy. He had a past history of granulomatous mediastinal lymphadenitis with positive histoplasmosis serology 11 years previously. Carpal tunnel exploration with biopsy demonstrated granulomatous inflammation. Granulomatous inflammation, hypercalcemia, and an elevated serum angiotensin converting enzyme (ACE) level suggested the diagnosis of sarcoidosis, however histoplasmosis infection could eventually be diagnosed. This unusual presentation of histoplasmosis underscores the fact that the diagnosis of sarcoidosis requires careful exclusion of other causes of granulomatous inflammation, particularly infectious agents. Even in the setting of an elevated ACE level and hypercalcemia, the possibility of an infectious etiology must be considered before establishing a diagnosis of sarcoidosis.