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Background: Renal impairment (RI) is one of the multiple myeloma (MM)-defining events for initiating therapy. After induction therapy, high-dose chemotherapy followed by autologous peripheral blood stem cell transplant (ASCT) remains the standard of care for transplant-eligible patients with MM. According to the International Myeloma Working Group (IMWG), the organ criterion for kidney damage is defined by a serum creatinine concentration (CrC) > 2 mg/dL or estimated glomerular filtration rate (eGFR) < 40 mL/min. In this long-term study, we evaluated the impact of CrC and eGFR calculated by the Modification of Diet in Renal Disease equation on progression-free and overall survival using a lower threshold than the IMWG criteria., Patients and Methods: We studied the longitudinal outcomes as measured by progression-free survival and overall survival in 59 transplant-eligible patients with MM: 38 patients with normal renal function and 21 patients with RI defined as a CrC higher than upper limit of normal (≥ 1.1 mg/dL), eGFR < 60 mL/min, treated with ASCT from 1998 to 2004., Results: The risk of disease progression and death following ASCT increased by 16.5% (P = .005) and 19% (P < .0009) per 1 mg/dL of CrC, respectively. The thresholds for the association of renal insufficiency and negative outcomes were CrC > 1.4 mg/dL and eGFR < 55mL/min., Conclusions: We observed a negative correlation between minimal renal insufficiency and long-term outcomes. Management of patients with even marginally increased CrC and/or decreased eGFR not fulfilling IMWG RI criteria requires more concentrated effort to reverse even minimal renal insufficiency., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Renal function (RF) and activities of daily living (ADL) are risk factors for heart failure (HF) patients., Aims: We evaluated differences in motor and cognitive ADL in relation to RF in elderly hospitalized HF patients., Methods: Participants were selected from 414 consecutive hospitalized HF patients based on certain criteria. We investigated patient characteristics including Functional Independence Measure (FIM) and estimated glomerular filtration rate (eGFR). Subjects were divided into three groups by RF level and analyzed with one-way ANOVA and Chi-square tests and two-way ANCOVA and multiple comparison tests., Results: Of the 414 patients, 165 met the inclusion criteria (high RF: 41, moderate RF: 84, low RF: 40). There were significant differences between the three groups in age, eGFR, hemoglobin level, mobility, cognitive function, and length of hospital stay (p < 0.05). Motor FIM showed an interaction between term and group, and cognitive FIM showed a main effect on the group (p < 0.05). In the multiple comparisons, motor FIM of all groups indicated significant recovery, but it was significantly lower after 1 week in the low RF versus moderate/high RF groups (p < 0.05). Cognitive FIM showed no significant recovery in the low RF group; the FIM score after 2 weeks was significantly lower than that in the moderate/high RF groups (p < 0.05)., Conclusions: In elderly hospitalized HF patients, the motor ADL recovery process in the low RF group was delayed compared to the high RF group. Cognitive ADL in hospitalized HF patients is difficult to recover, especially in those with low RF.

The Joint Committee on Diabetic Nephropathy has revised its Classification of Diabetic Nephropathy (Classification of Diabetic Nephropathy 2014) in line with the widespread use of key concepts such as the estimated glomerular filtration rate (eGFR) and chronic kidney disease. In revising the Classification, the Committee carefully evaluated, as relevant to current revision, the report of a study conducted by the Research Group of Diabetic Nephropathy, Ministry of Health, Labour and Welfare of Japan. Major revisions to the Classification are summarized as follows: (1) eGFR is substituted for GFR in the Classification; (2) the subdivisions A and B in stage 3 (overt nephropathy) have been reintegrated; (3) stage 4 (kidney failure) has been redefined as a GFR less than 30 mL/min/1.73 m(2), regardless of the extent of albuminuria; and (4) stress has been placed on the differential diagnosis of diabetic nephropathy versus non-diabetic kidney disease as being crucial in all stages of diabetic nephropathy.

Background: The National Kidney Foundation's Kidney Disease Outcomes Quality Initiative (NKF's KDOQI) staging system for chronic kidney disease (CKD) is based primarily on estimated GFR (eGFR). This study aimed at assessing whether reclassification of subjects with type 2 diabetes using two recent classifications based on both eGFR and albuminuria, the Alberta Kidney Disease Network (AKDN) and the Kidney Disease: Improving Global Outcomes (KDIGO), provides a better definition of burden from cardiovascular disease (CVD) and diabetic retinopathy (DR) than the NKF's KDOQI classification., Methods: This is a cross-sectional analysis of patients with type 2 diabetes (n = 15,773) from the Renal Insufficiency And Cardiovascular Events Italian Multicenter Study, consecutively visiting 19 Diabetes Clinics throughout Italy in years 2007-2008. Exclusion criteria were dialysis or renal transplantation. CKD was defined based on eGFR, as calculated from serum creatinine by the simplified Modification of Diet in Renal Disease Study equation, and albuminuria, as measured by immunonephelometry or immunoturbidimetry. DR was assessed by dilated fundoscopy. Prevalent CVD, total and by vascular bed, was assessed from medical history by recording previous documented major acute events., Results: Though prevalence of complications increased with increasing CKD severity with all three classifications, it differed significantly between NKF's KDOQI stages and AKDN or KDIGO risk categories. The AKDN and KDIGO systems resulted in appropriate reclassification of uncomplicated patients in the lowest risk categories and a more graded independent association with CVD and DR than the NKF's KDOQI classification. However, CVD, but not DR prevalence was higher in the lowest risk categories of the new classifications than in the lowest stages of the NKF's KDOQI, due to the inclusion of subjects with reduced eGFR without albuminuria. CVD prevalence differed also among eGFR and albuminuria categories grouped into AKDN and KDIGO risk category 1 and moderate, respectively, and to a lesser extent into higher risk categories., Conclusions: Though the new systems perform better than the NKF's KDOQI in grading complications and identifying diabetic subjects without complications, they might underestimate CVD burden in patients assigned to lower risk categories and should be tested in large prospective studies., Trial Registration: ClinicalTrials.gov; NCT00715481.

Objective: To evaluate long-term renal outcomes after open type IV thoracoabdominal aneurysm (TAAA) repair., Design: Retrospective analysis of a prospectively collected database of consecutive operated non-ruptured type IV TAAAs (2007-2011)., Methods: Renal function was analysed by serum creatinine concentration, estimated glomerular filtration rate (eGFR) and Kidney Disease Outcomes Quality Initiative (KDOQI) stage. The primary outcome was the change in creatinine concentration from before surgery to defined time points after surgery: peak postoperative; discharge; at follow-up (>1 year postoperatively). Secondary outcomes were change in eGFR, change in KDOQI stage, dialysis requirement, and 30-day mortality., Results: Between 2007 and 2011, 53 open type IV TAAA repairs were performed. Median creatinine levels significantly increased in the immediate postoperative period, but returned to baseline by discharge. Thirteen patients (28.2%) had an improvement in follow-up eGFR of at least 20% compared with pre-operative eGFR or improved by one KDOQI stage. Twelve patients (26.1%) had a decline in eGFR of at least 20% or one KDOQI stage at follow-up. Three patients (7.5%) required temporary dialysis and one patient (1.9%) required permanent dialysis. The 30-day mortality was 1.9%., Conclusions: This study demonstrates acceptable renal outcomes following open type IV TAAA repair. Open type IV repair remains the standard against which newer techniques should be compared., (Copyright © 2013. Published by Elsevier Ltd.)

The aim of the Best Practice guidelines on peritoneal ultrafiltration (UF) in patients with treatment-resistant advanced decompensated heart failure (TR-AHDF) is to achieve a common approach to the management of decompensated heart failure in those situations in which all conventional treatment options have been unsuccessful, and to stimulate a closer cooperation between nephrologists and cardiologists. The standardization of the case series of different centers would allow a better definition of the results published in the literature, without which they are nothing more than anecdotes. TR-AHDF is characterized by the persistence of severe symptoms even when all possible pharmacological and surgical options have been exhausted. These patients are often treated with methods that allow extracorporeal UF - slow continuous ultrafiltration (SCUF) and continuous renal replacement therapy (CRRT) - which have to be performed in hospital facilities. Peritoneal ultrafiltration (PUF) can be considered a treatment option in patients with TR-AHDF when, despite the fact that all treatment options have been used, patients meet the following criteria: • stage D decompensated heart failure (ACC/AHA classification); • INTERMACS level 4 decompensated heart failure; • INTERMACS frequent flyer profile; • chronic renal failure (estimated glomerular filtration rate <50 ml/min per 1.73 m2: KDOQI classification stage 3 chronic kidney disease); • no obvious contraindications to peritoneal UF. PUF treatment modes are derived from the treatment regimens proposed by various authors to obtain systemic UF in patients with severe decompensated heart failure, using manual and automated incremental peritoneal dialysis involving various glucose concentrations in addition to the single icodextrin exchange. These guidelines also identify a minimum set of tests and procedures for the follow-up phase, to be supplemented, according to the center's resources and policy, with other tests that are less routine or more complex also from a logistic/organizational standpoint, emphasizing the need for the patient's clinical and treatment program to involve both the nephrologist and the cardiologist. The pathophysiological aspects of a deterioration in kidney function in patients with decompensated heart failure are also considered, and the results of PUF in patients with decompensated heart failure reported in the various case series are reviewed.

Background: Renal dysfunction is one of the most common complications of cirrhosis with high morbidity and mortality., Summary: In subjects with cirrhosis, renal dysfunction can present either as a direct consequence of cirrhosis (e.g. hepatorenal syndrome type I and type II) or secondary to etiologies other than cirrhosis (chronic kidney disease due to diabetic nephropathy, prerenal azotemia), or patients with cirrhosis may have renal dysfunction resulting directly from cirrhosis and an underlying chronic kidney disease., Key Messages: Given the challenges in the differential diagnosis of renal dysfunction and insufficient accuracy of serum creatinine and creatinine-based glomerular filtration rate estimating equations in cirrhosis, there is an urgent need for more accurate biomarkers of renal dysfunction in this population. This review will discuss novel concepts for the diagnosis and classification of renal dysfunction in cirrhosis to overcome at least some of the diagnostic and therapeutic challenges. Additionally, a new classification will be proposed for renal dysfunction in cirrhosis., (© 2013 S. Karger AG, Basel.)

Cardiac and kidney diseases are very common, and increasingly coexist. Classification for cardiorenal syndrome and for its specific subtypes has been developed and published recently by a consensus group of the Acute Dialysis Quality Initiative. Cardiorenal syndromes have been classified according to whether the impairment of each organ is primary, secondary or whether heart and kidney dysfunction occurs simultaneously as a systemic disease. The different syndromes were classified into five subtypes. Type-1: acute cardiorenal syndrome: an abrupt worsening of cardiac function leading to acute kidney injury and/or dysfunction. Type-2: chronic cardiorenal syndrome: chronic abnormalities in cardiac function causing kidney injury and/or dysfunction. Type-3: acute renocardiac syndrome: abrupt worsening of kidney function leading to heart injury and/or dysfunction. Type-4: chronic renocardiac syndrome: chronic kidney diseases leading to heart injury, disease and/or dysfunction. Type-5: secondary cardiorenal syndrome: acute or chronic systemic diseases leading to simultaneous injury and/or dysfunction of heart and kidney. The identification of patients and the pathophysiological mechanisms underlying each syndrome subtype will help cardiologists, nephrologists and physicians working on intensive care units to characterize groups of their patients with cardiac and renal impairment and to provide a more accurate treatment for them.

What drives human beings to classify? It seems as if it is within our nature to do so. Clinical classification systems for the systemic vasculitides were composed a long time ago, and they are constantly being revised and altered. The histopathological features of many diseases are so diverse that classification is called for. The histopathological classification for anti-neutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis was the culmination of results produced from a number of clinicopathological studies conducted within the European Vasculitis Study Group (EUVAS). The classification scheme has four general categories, named focal, crescentic, sclerotic and mixed. The first three categories are based on the predominance of normal glomeruli, glomeruli with cellular crescents and globally sclerotic glomeruli. The mixed category represents a heterogeneous phenotype of biopsies in which none of the aforementioned features is dominant. Results from a validation study incorporating 100 patients with at least 1-year follow-up showed that the phenotypical order of the four classes corresponded to the severity of renal function impairment. The new histopathological classification for ANCA-associated glomerulonephritis provides a logical structure for the categorization of patients into four subgroups defined according to glomerular features. This classification will be of use for future studies, such as clinical trials., (© 2011 The Author; Clinical and Experimental Immunology © 2011 British Society for Immunology.)

Patients with chronic kidney disease (CKD) are at high risk for major cardiovascular (CV) morbidity and mortality, especially when they range among the elderly. The co-existence of renal dysfunction is common in patients with chronic heart failure (CHF), and renal failure is among the strongest predictors of mortality in patients with heart failure. Approximately one-third of dialysis patients also suffer from heart failure. The term "cardiorenal syndrome" has been increasingly described in recent literature, as there is growing recognition of the frequent association of combined renal and cardiac dysfunction. The pathophysiology of the cardiorenal syndrome involves interrelated hemodynamic and neurohormonal mechanisms, including the sympathetic nervous system, the renin-angiotensin-aldosterone system, and endothelin and arginine vasopressin system activation. Recently, a new classification of cardiorenal syndrome has been proposed with five subtypes that reflect the pathophysiology, the bidirectional nature of heart and kidney interaction and the time-frame. The management of the cardiorenal syndrome remains a challenge in spite of the advances in medical therapy and novel agents. Novel agents such as B-type natriuretic peptide (BNP) derivative, endothelin antagonist, adenosine antagonist or vasopressin antagonist have been evaluated in randomized controlled trials, and their results are discussed in this review. Mechanical support like hemodialysis and ultrafiltration are found to be useful in acute cardiorenal syndrome. There has been renewed interest in b-blockers in chronic cardiorenal syndrome patients to prevent sudden cardiac death from arrhythmia. In this review, we discuss the evidence behind the definition, pathophysiology, new proposed classification and the various therapeutic measures available for acute cardiorenal syndrome as well as chronic cardiorenal syndrome.

Cardiac and renal dysfunction of different degree is common combination in patients in clinical practice. This combination of cardiovascular and renal injury has been defined as a cardiorenal syndrome. The aim of this paper is to offer a comprendious information about actual insights into pathophysiology, terminology, classification and management of cardiorenal syndrome from cardiologist's point of view.

Concomitant cardiac and renal dysfunction has been termed the cardiorenal syndrome (CRS). This clinical condition usually manifests as heart failure with worsening renal function and occurs frequently in the acute care setting. A consistent definition of CRS has not been universally agreed upon, although a recent classification of CRS describes several subtypes depending on the primary organ injured and the chronicity of the injury. CRS may develop in adults and children and is a strong predictor of morbidity and mortality in hospitalized and ambulatory patients. The underlying physiology of CRS is not well understood, creating a significant challenge for clinicians when treating heart failure patients with renal insufficiency. This review summarizes recent data characterizing the incidence, physiology, and management of children who have heart failure and acute kidney injury.

The present review describes recent evidence on all aspects relating to acute kidney injury (AKI): epidemiology, definition, diagnosis, medical and extracorporeal therapy. AKI is often underrecognized, but its outcome still remains unfavorable. In this light, definition, classification and diagnosis of AKI are fundamental today and may be reliably based on recently proposed RIFLE (risk, injury, failure, loss of function, end-stage kidney disease) classification. Pharmacological therapy of AKI is still scarcely effective, but renal replacement therapy has progressed to a more accurate and safe treatment and new interesting high-level trials and observational studies have been performed and are reviewed and commented. In the near future, however, only increased awareness of AKI incidence and early treatment or prevention of kidney injury progression will hopefully improve outcome of critically ill patients with renal failure.

The term cardiorenal syndrome (CRS) increasingly has been used without a consistent or well-accepted definition. To include the vast array of interrelated derangements, and to stress the bidirectional nature of heart-kidney interactions, we present a new classification of the CRS with 5 subtypes that reflect the pathophysiology, the time-frame, and the nature of concomitant cardiac and renal dysfunction. CRS can be generally defined as a pathophysiologic disorder of the heart and kidneys whereby acute or chronic dysfunction of 1 organ may induce acute or chronic dysfunction of the other. Type 1 CRS reflects an abrupt worsening of cardiac function (e.g., acute cardiogenic shock or decompensated congestive heart failure) leading to acute kidney injury. Type 2 CRS comprises chronic abnormalities in cardiac function (e.g., chronic congestive heart failure) causing progressive chronic kidney disease. Type 3 CRS consists of an abrupt worsening of renal function (e.g., acute kidney ischemia or glomerulonephritis) causing acute cardiac dysfunction (e.g., heart failure, arrhythmia, ischemia). Type 4 CRS describes a state of chronic kidney disease (e.g., chronic glomerular disease) contributing to decreased cardiac function, cardiac hypertrophy, and/or increased risk of adverse cardiovascular events. Type 5 CRS reflects a systemic condition (e.g., sepsis) causing both cardiac and renal dysfunction. Biomarkers can contribute to an early diagnosis of CRS and to a timely therapeutic intervention. The use of this classification can help physicians characterize groups of patients, provides the rationale for specific management strategies, and allows the design of future clinical trials with more accurate selection and stratification of the population under investigation.

Contrast-induced nephropathy (CIN) after percutaneous coronary intervention (PCI) has multiple definitions. We attempted to identify the optimal definition of CIN. In 985 patients undergoing PCI (derivation group), we assessed the prognostic significance of 4 commonly used contemporary definitions of CIN (increases in serum creatinine after PCI [deltaCr] >1.0 mg/dl, >0.5 mg/dl, and >25% after PCI; and the American College of Cardiology National Cardiovascular Data Registry definition) with respect to 6-month major adverse cardiovascular events (MACEs) and all-cause mortality (at 863 +/- 324 days). Incidence of CIN ranged widely (2.0% to 15%) depending on the definition used. Only 2 definitions (deltaCr >0.5 mg/dl, >25%) consistently correlated with study outcomes. Using these 2 definitions, we devised a new grading system (grade 0 deltaCr 25% but 0.5 mg/dl). Nephropathy grades (0 vs 1 vs 2) showed significant correlation with 6-month MACEs (12.4 vs 19.4 vs 28.6%, p = 0.003) and all-cause mortality (10.2 vs 10.4 vs 40.9%, p <0.0001). In multivariate analyses, the grading system showed an independent association with MACEs and mortality. The prognostic value of nephropathy grades was prospectively confirmed in an independent validation group of 539 patients. In conclusion, of the 4 contemporary definitions of CIN, only deltaCr >25% and >0.5 mg/dl consistently predicted adverse events after PCI. By unifying these 2 definitions, we devised a novel nephropathy grading system that is predictive of 6-month MACEs and all-cause mortality after PCI.

The most widely used peritoneal function test is the peritoneal equilibration test (PET), developed and described by Twardowski in 1987. PET is performed using a 2.27% glucose solution and it lasts 4 hours. It measures peritoneal solute transport and ultrafiltration. PET gives the possibility to categorise patients (high, high-average, low-average and low transporters). However, a PET with 3.86% glucose provides better information on ultrafiltration and the phenomenon of sodium sieving provides an assessment of free water transport. Two recently developed tests (Mini-PET, Double Mini-PET) are promising tools to assess the free water transport and the osmotic conductance to glucose. The above new insights in the peritoneal function need of a new standardization of the PET. It possible that the ''new PET'' will be performed by a machine (PET-machine) in order to avoid the mistakes during the performance of manual PET and to allow an universal standardization of the test.

Background: The diagnosis of acute rejection (AR) relies on biopsy (Bx), with all the noninvasive tests failing to show satisfactory predictive value. Nitric oxide (NO) has been shown to play a role in AR. The aim of this study is to analyze the relationship between NO and (1) biopsy-proven allograft rejection and (2) other reasons of allograft dysfunction., Patients and Methods: Fifty consecutive renal allograft recipients ages 23-72 yrs who were transplanted were prospectively recruited. Blood samples were collected for 3 months. Endogenous serum nitrate (SNO(3)) levels were measured with Griess reagent in 1178 samples. Biopsies were performed as clinically indicated. Tacrolimus levels, urinary cultures, and renal function tests were done as per unit protocol., Results: Fifty recipients (mean+/-SD age 45.2+/-2.18 yrs, 24 men and 6 women) underwent 68 biopsies. Forty-five Bx (66.2%) showed AR in 19 recipients (mean age 47+/-8) and 23 (33.8%) Bx in 13 recipients (mean age 43+/-12) showed no AR. SNO(3) in AR was (73+/-8.89 micromol/L) compared with negative Bx (45+/-4.5 micromol/L; P<0.05). There was also a significant difference in SNO(3) during AR and other causes of allograft dysfunction; delayed graft function (54+/-7.8 micromol/L), urinary tract infection (44+/-2.9 micromol/L), tacrolimus toxicity (51+/-2.86 micromol/L), and increase in serum creatinine (44+/-2.36 micromol/L)., Conclusion: There is a significant increase of serum nitrate with episodes of acute rejection compared with other causes of renal dysfunction. SNO(3) can therefore aid in the diagnosis of acute rejection.

Objectives: To estimate in a community-dwelling elderly population the magnitude of renal function misclassification, occurring when persons with normal serum creatinine have reduced glomerular filtration rate (GFR), and to describe the participant characteristics related to misclassification., Design: Cross-sectional., Setting: Population-based study of older Italian people., Participants: Six hundred sixty participants aged 65 to 92 with normal serum creatinine., Measurements: GFR was estimated using the Cockcroft-Gault equation and creatinine clearance (CrCl) calculated from 24-hour urine collection., Results: In participants with normal serum creatinine, 39% and 25% had moderate renal function impairment (GFR<60 mL/min) according to the Cockcroft-Gault equation and CrCl calculation, respectively. Prevalence of moderate renal impairment in those aged 65 to 74, 75 to 84, and 85 and older was 18.6%, 58.3%, and 96.8%, respectively (P for trend <.001) according to the Cockcroft-Gault equation, and 15%, 35.7%, and 58.7%, respectively (P for trend <.001) based on the CrCl calculation. In addition, female sex (P<.001) and normal or underweight (P<.05) were factors associated with high risk of misclassification., Conclusion: Serum creatinine alone is one of the most widely used methods of assessing renal function in clinical practice despite its well-known poor correlation with GFR. A large proportion of older persons with impaired renal function are not diagnosed if clinicians rely solely on normal serum creatinine as evidence of normal renal function. Opportunities may be missed for slowing progression of kidney disease, managing comorbidities and complications related to renal impairment, and adjusting drug dosage for renal function.

Background: Several proposed definitions for acute renal failure (ARF) exist, but little is known of their significance in clinical practice. We evaluated the ability to predict hospital mortality in 2 ARF-specific severity-of-illness scoring methods, the Risk, Injury, Failure, Loss, End-Stage Renal Disease (RIFLE) score and the score presented by Bellomo et al in 2001., Methods: The study included 668 consecutive patients with 694 treatment episodes treated in 2 intensive care units (ICUs) in a university hospital within 11 months. ARF prevalence was classified according to the RIFLE and Bellomo scores. As references, we evaluated 2 general severity-of-illness scoring systems, the admission Acute Physiology and Chronic Health Evaluation II (APACHE II) and Sequential Organ Failure Assessment (SOFA) scores., Results: Admission SOFA scores and maximum RIFLE scores for the first 3 days in the ICU were independent predictors of hospital mortality by means of forward conditional logistic regression. In receiver operating characteristic analysis, SOFA and APACHE II scores performed better than ARF-specific scores, and discriminative powers for hospital mortality were only moderate for the RIFLE and Bellomo scores: areas under the curve were 0.653 (95% confidence interval, 0.588 to 0.719) and 0.587 (95% confidence interval, 0.514 to 0.660), respectively., Conclusion: Neither of the ARF-specific scoring methods presented good discriminative power regarding hospital mortality. However, maximum RIFLE score for the first 3 days in the ICU was found to be an independent predictor of hospital mortality, along with admission SOFA score.

The purpose of this study was to examine whether HIV infection affects either the echographic or laboratory profiles of renal insufficiency. This prospective study compared both echographic (kidney size, Hricak's cortical echogenicity grades) and laboratory (blood urea and creatine) profiles in two groups of patients with renal insufficiency: one group HIV-positive (25 cases) and the other HIV-negative (86 patients). Kidney size was generally normal in the HIV-negative group. In the HIV-positive group, it was either normal or enlarged, especially in thickness, with a spherical appearance. Echogenicity grades were high in both groups, and no HIV-positive patients were at grade I; 25.6% of the seronegative patients and 20% of seropositive patients were at grade II, and 57% and 68%, respectively, were at grade III. The correlation between ultrasound grades and laboratory results did not differ significantly between the two groups (p = 0.0669 for creatinemia and p = 0.0560 for uremia), although the rates tended to increase with echogenicity grade and were slightly lower in the HIV-positive group. The authors conclude that HIV infection does not seem to affect the ultrasound or laboratory profiles of renal insufficiency. Thickening of the kidney and any spherical aspect should however suggest to the practitioner that the renal insufficiency may be related to HIV.

To assess the safety, pharmacokinetics, and pharmacodynamics of febuxostat in subjects with normal renal function or renal impairment, febuxostat (80 mg/d) was orally administered for 7 days to subjects with normal renal function (n = 11, CLcr >80 mL/min/1.73 m) or to subjects with mild (n = 6, CLcr 50-80 mL/min/1.73 m), moderate (n = 7, CLcr 30-49 mL/min/1.73 m), or severe renal impairment (n = 7, CLcr 10-29 mL/min/1.73 m). The pharmacokinetics of febuxostat and its active quantifiable metabolites 67M-1, 67M-2, and 67M-4 as well as the pharmacodynamics of uric acid, xanthine, and hypoxanthine were determined in plasma (or serum) and urine. Febuxostat was safe and well tolerated. Regression analyses indicated that febuxostat tmax and Cmax,u values were not affected by CLcr. However, for AUC24,u, CLu/F, and t1/2z, regression analyses indicated a statistically significant relationship with CLcr. With the exception of 67M-1 Cmax, regression analyses for 67M-2 and 67M-4 Cmax, and for AUC24 for all 3 metabolites indicated a statistically significant linear relationship with CLcr. Irrespective of renal function group, the mean serum uric acid concentrations decreased by 55% to 64% by day 7. Although plasma exposure to febuxostat and its metabolites was generally higher in subjects with increasing degrees of renal impairment, the percentages of decrease in serum uric acid were comparable regardless of the renal function group. A once-daily 80-mg dose of febuxostat appears to be safe and well tolerated in different renal function groups and does not appear to require any dose adjustment based on differences in renal function.

Clinical trials have demonstrated that angiotensin-converting enzyme (ACE) inhibitors, beta-blockers, and spironolactone improve survival in patients with heart failure. Because patients with heart failure and renal insufficiency have been underrepresented in these trials, little evidence is available to guide clinicians in the optimal management of patients with both conditions. Approximately one third to one half of patients with heart failure have renal insufficiency (estimated glomerular filtration rate [GFR] <60 mL/min per 1.73 m2), and renal insufficiency is among the strongest predictors of mortality in patients with heart failure. Evidence supports the use of ACE inhibitors to improve survival in patients with moderate renal insufficiency (GFR, 30 to 60 mL/min per 1.73 m2), but there is little evidence with which to weigh the risks and benefits in patients with more advanced renal dysfunction. beta-Blockers improve survival in patients with heart failure, and their beneficial effect is unlikely to differ according to renal function. Spironolactone improves outcomes in patients with advanced heart failure, but renal insufficiency appears to increase risk for hyperkalemia and limits the use of the drug in patients with severe renal insufficiency. Future clinical trials in heart failure should include a representative number of patients with renal insufficiency to improve the evidence base and outcomes in this vulnerable population.

Enoxaparin is a low molecular weight heparin (LMWH) that has been shown to be effective in deep vein thrombosis, pulmonary embolism, and unstable angina. Because renal function plays an important role in the clearance of LMWH, the authors sought to investigate the effect of renal function on enoxaparin. This prospective multiple-dose study evaluated 18 patients with varying degrees of renal function initiated on enoxaparin 1 mg/kg subcutaneously every 12 hours. Peak blood levels of anti-Xa concentrations were obtained 4 +/- 0.5 hours postdose after receiving at least three doses of enoxaparin. The median antifactor Xa levels were higher in patients with creatinine clearance (CLCr) < or = 30 mL/min compared to CLCr > or = 31 mL/min (1.34 IU/mL vs. 0.91 IU/mL, respectively, p < 0.05). A linear correlation was established between creatinine clearance and anti-Xa concentrations (p < 0.0005). On the basis of the data, the authors believe that a dose adjustment is necessary in patients receiving repeated doses of enoxaparin with CLCr < or = 30 mL/min.

The present study was performed to ascertain whether the presence of mild renal failure (defined as a serum creatinine concentration of 1. 5 to 3.0 mg/dL) is an independent risk factor for adverse outcome after cardiac valve surgery. An extensive set of preoperative and postoperative data was collected in 834 prospectively evaluated patients undergoing cardiac valve surgery at 14 Veterans Affairs Medical Centers. Univariate and multivariable analyses were performed to determine whether an independent association of mild renal dysfunction with adverse outcomes was present. Patients with mild renal failure had significantly greater 30-day mortality rates (P = 0.001; 16% versus 6%) and frequency of postoperative bleeding (P = 0.023; 16% versus 8%), respiratory complications (P = 0.02, 29% versus 16%), and cardiac complications (P = 0.002; 18% versus 7%) than patients with normal renal function (serum creatinine <1.5 mg/dL) when controlling for multiple other variables. The presence of a serum creatinine concentration of 1.5 to 3.0 mg/dL is significantly and independently associated with adverse outcomes after cardiac valve surgery.

Sparfloxacin is a fluoroquinolone antimicrobial agent with a broad spectrum of activity and long elimination half-life. Because its single-dose pharmacokinetics are altered by renal impairment, the present study was undertaken to determine the effects of moderate or severe renal insufficiency on the multidose pharmacokinetic characteristics of and tolerance to sparfloxacin. The pharmacokinetic characteristics of sparfloxacin were assessed in 32 subjects (15 men, 17 women) with (1) normal renal function (creatinine clearance [CLcr]> or = 250 mL/min per 1.73 m2) and a mean age of 52.6 years and mean weight of 70.4 kg; (2) moderate renal insufficiency (CLcr 30-49 mL/min per 1.73 m2) and a mean age of 54.4 years and mean weight of 67.8 kg; and (3) severe renal insufficiency (CLcr 10-29 mL/min per 1.73 m2) and a mean age of 50.8 years and mean weight of 73.1 kg. The first 2 groups received a 400-mg loading dose on day 1 followed by 200 mg once daily for 9 days; subjects with severe renal insufficiency received a 400-mg loading dose on day 1 followed by 200 mg every 48 hours on days 3, 5, 7, and 9. The plasma and urinary pharmacokinetics of sparfloxacin and its glucuronide metabolite were determined after the last dose. All subjects were monitored for changes in the corrected QT (QTc) interval and for adverse events. Renal insufficiency altered the steady-state pharmacokinetic variables of sparfloxacin and its glucuronide metabolite, reducing their renal clearances and increasing both maximum plasma concentration and area under the plasma concentration-time curve. Mean steady-state plasma sparfloxacin concentrations in subjects with severe renal insufficiency (48-hour dosing interval) were comparable to those in subjects with normal renal function (24-hour dosing interval). However, mean plasma sparfloxacin concentrations in patients with moderate renal insufficiency were 2 to 3 times greater than the corresponding concentrations in subjects with normal renal function receiving the same dosage regimen. The QTc interval was slightly increased in all groups (the greatest increases were 14, 14, and 6 milliseconds in the groups with normal renal function and moderately and severely impaired renal function, respectively, at 5.5 hours post-dose on day 9 or 10) but similar among subjects with normal renal function or with renal insufficiency. Sparfloxacin was well tolerated. Thus sparfloxacin clearance is reduced and plasma concentrations raised by moderate or severe renal insufficiency. These increases do not appear to augment drug effects on the QTc interval or enhance the risk for adverse events. These results suggest that alternate-day dosing (48-hour dosing interval) following a double loading dose on day 1 should be used in patients with severe renal insufficiency and may be appropriate for patients with moderate renal insufficiency.

Objective: The pharmacokinetics of cilostazol were studied in patients with mild, moderate and severe renal impairment and in healthy volunteers after administration of 50 mg single and multiple doses of cilostazol., Design: This was an open-label, single and multiple dose study administering 50 mg cilostazol every 12 hours to healthy volunteers and patients with varying degrees of renal impairment., Participants: 6 normal volunteers [creatinine clearance (CLCR) > or = 90 ml/min]; 6 patients with mild (CLCR 50 to 89 ml/min), 5 with moderate (CLCR 26 to 49 ml/min) and 6 with severe (CLCR 5 to 25 ml/min) renal impairment., Outcome Measures: Noncompartmental pharmacokinetic parameters were determined for each study participant., Results: At steady state, in the severe renal disease group, cilostazol and OPC-13015 peak concentrations (Cmax) were 29 and 41% lower and the areas under the concentration-time curve over the dosage interval (AUC tau) 39 and 47% lower than in the healthy volunteers. Cmax and AUC tau of OPC-13213 were significantly higher, 173 and 209%, respectively, than those in the healthy volunteers. The accumulation ratios were not significantly different between the various renal function groups for cilostazol and its metabolites. The estimated pharmacological activity of cilostazol and its metabolites was similar between the normal volunteers and those with severe renal impairment., Conclusions: A dosage reduction in renally impaired patients is not supported by the pharmacokinetics of cilostazol and its metabolites in this patient group.