Use of peritoneal dialysis in AKI: a systematic review.

BACKGROUND AND OBJECTIVES: The role of peritoneal dialysis in the management of AKI is not well defined, although it remains frequently used, especially in low-resource settings. A systematic review was performed to describe outcomes in AKI treated with peritoneal dialysis and compare peritoneal dialysis with extracorporeal blood purification, such as continuous or intermittent hemodialysis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: MEDLINE, CINAHL, and Central Register of Controlled Trials were searched in July of 2012. Eligible studies selected were observational cohort or randomized adult population studies on peritoneal dialysis in the setting of AKI. The primary outcome of interest was all-cause mortality. Summary estimates of odds ratio were obtained using a random effects model. RESULTS: Of 982 citations, 24 studies (n=1556 patients) were identified. The overall methodological quality was low. Thirteen studies described patients (n=597) treated with peritoneal dialysis only; pooled mortality was 39.3%. In 11 studies (7 cohort studies and 4 randomized trials), patients received peritoneal dialysis (n=392, pooled mortality=58.0%) or extracorporeal blood purification (n=567, pooled mortality=56.1%). In the cohort studies, there was no difference in mortality between peritoneal dialysis and extracorporeal blood purification (odds ratio, 0.96; 95% confidence interval, 0.53 to 1.71). In four randomized trials, there was also no difference in mortality (odds ratio, 1.50; 95% confidence interval, 0.46 to 4.86); however, heterogeneity was significant (I(2)=73%, P=0.03). CONCLUSIONS: There is currently no evidence to suggest significant differences in mortality between peritoneal dialysis and extracorporeal blood purification in AKI. There is a need for good-quality evidence in this important area.

Medical management of renal stone.

Kidney stone is a common clinical problem faced by clinicians. The prevalence of the disease is increasing worldwide. As the affected population is getting younger and recurrence rates are high, dietary modifications, lifestyle changes, and medical management are essential. Patients with recurrent stone disease need careful evaluation for underlying metabolic disorder. Medical management should be used judiciously in all patients with kidney stones, with appropriate individualization. This chapter focuses on medical management of kidney stones.

Cardiorenal Syndrome Type 1 May Be Immunologically Mediated: A Pilot Evaluation of Monocyte Apoptosis.

BACKGROUND: Cardiorenal syndrome (CRS) type 1 is characterized by a rapid worsening of cardiac function leading to acute kidney injury (AKI). An immune-mediated damage and alteration of immune response have been postulated as potential mechanisms involved in CRS type 1. In this pilot study, we examined the possible role of the immune-mediated mechanisms in the pathogenesis of this syndrome. The main objective was to analyze in vitro that plasma of CRS type 1 patients was able to trigger a response in monocytes resulting in apoptosis. The secondary aim was to evaluate TNF-α and IL-6 plasma levels of CRS type 1 patients. METHODS: Fifteen patients with acute heart failure (AHF) and CRS type 1 were enrolled and 20 healthy volunteers without AHF or AKI were recruited as control group. Plasma from these two groups was incubated with monocytes and, subsequently, cell apoptosis was evaluated. In addition, the activity of caspase-8 was assessed after 24 h incubation. Quantitative determination of TNF-α and IL-6 levels was performed. RESULTS: Plasma-induced apoptosis was significantly higher in CRS type 1 patients compared with healthy controls at 72 h (78 vs. 11%) and 96 h (81 vs. 11%). At 24 h, the activity of caspase-8 was significantly higher in monocytes incubated with plasma from the CRS type 1 group. TNF-α (2.39 vs. 28.49 pg/ml) and IL-6 (4.8 vs. 16.5 pg/ml) levels were significantly elevated in the CRS type 1 group (p < 0.01). CONCLUSIONS: In conclusion, there is a defective regulation of monocyte apoptosis in CRS type 1 patients, and inflammatory pathways may have a central role in the pathogenesis of CRS type 1 and may be fundamental in damage to distant organs.

Cardio-renal syndrome type 5: epidemiology, pathophysiology, and treatment.

The cardio-renal syndromes (CRS) recently were defined systematically as disorders of the heart or kidney whereby dysfunction of one organ leads to dysfunction of another. Five types of CRS are defined. The first four types describe acute or chronic cardio-renal or renocardiac syndromes. Type 5 CRS refers to secondary cardio-renal syndrome or cardio-renal involvement in systemic conditions. It is a clinical and pathophysiological entity to describe the concomitant presence of renal and cardiovascular dysfunction. Type 5 CRS can be acute or chronic and it does not strictly satisfy the definition of CRS. However, it encompasses many conditions in which combined heart and kidney dysfunction is observed. Because this entity has been described only recently there is limited information about the epidemiology, clinical course, and treatment of this condition.

New biomarkers for acute renal injury.

Incidence of acute kidney injury (AKI) is increasing rapidly to epidemic proportions. Development of AKI, especially in intensive care settings, is associated with increased morbidity, mortality and hospitalization costs. Currently available diagnostic tools are mostly insensitive for early diagnosis, however prompt diagnosis and risk stratification are necessary for guiding therapy and preventing progression of disease. Finding an early, reliable, suitable, easily reproducible, economical and accurate biomarker for AKI is a top research priority. In recent years, many urinary and serum proteins have been investigated as possible early markers of AKI and some of them have shown great promise. This topic reviews some of the emerging biomarkers of AKI.

Hepatitis C virus adversely affects quality of life.

BACKGROUND: Chronic liver disease secondary to hepatitis C virus (HCV) infection is a common clinical problem. HCV is likely to adversely affect the quality of life (QoL) of the patient. This effect is said to be disproportionate to the severity of the disease. The aim of our study was to evaluate QoL in HCV-positive patients focusing both on health status and subjective satisfaction. METHODS: Twenty-four patients with combined HCV and alcoholic liver disease (ETOH-HCV) were enrolled in the study. We adopted two generic tools: SF-36 (a health status questionnaire) and SAT-P (a satisfaction profile) for psychological assessment of the patients. SF-36 and SAT-P scores of ETOH-HCV patients were compared with scores of 23 patients with alcoholic liver disease (ETOH). The scores obtained from the study groups were also compared with the reference scores of the healthy Italian population. RESULTS: Both the groups were comparable with respect to age, histological and clinical severity of liver disease (as assessed by MELD and Child Pugh scores). Patients with ETOH-HCV scored less in the vitality and role emotional status domains of the SF-36 scores and the psychological function, social function and free time domains of the satisfaction profile. CONCLUSIONS: These results show a significant impact of HCV infection on health status and subjective satisfaction.

Collagenofibrotic glomerulopathy in association with Hodgkin's lymphoma.

Deposit glomerulopathies are characterized by fibrillary deposits of various sizes, mainly in the mesangial area. Collagenofibrotic glomerulopathy is a rare type of such fibrillary glomerulopathies characterized by deposits of 60-80 nm fibrils in the sub-endothelial and mesangial areas. It is also associated with increased levels of serum pro-collagen type III peptide (PIIINP). Although most of the initial reports have emanated from Japan, many other scientists around the globe have later reported this disease. Possibility of systemic disease affecting metabolism of type III collagen is postulated but so far no such association has been identified. We report a 26-year-old male patient who presented with insidious onset of febrile illness associated with lymphadenopathy and proteinuria. Lymph node biopsy revealed features of Hodgkin's lymphoma while percutaneous renal biopsy showed features of collagenofibrotic glomerulopathy.

Removal of neutrophil gelatinase-associated lipocalin by extracorporeal therapies.

Neutrophil gelatinase-associated lipocalin (NGAL) protein is an early biomarker for acute kidney injury (AKI). It is unknown if extracorporeal therapies (EC) have an effect on circulating NGAL levels. This study was designed to describe the kinetics of NGAL molecule in different EC techniques and to evaluate NGAL clearance in different operational conditions. A mock hemofiltration (HF) and hemoperfusion (HP) setup was used. NGAL was added to the blood reservoir and then measured at 30-minute intervals from arterial, venous, and ultrafiltrate (UF) lines. Removal kinetics and NGAL sieving coefficient were calculated. In our experiments, baseline NGAL concentration averaged 452 microg/L. There was a consistent downward trend throughout the experiment. NGAL concentration in the UF was between 80 and 90 microg/L, though it showed a slight increase in the second hour. The sieving coefficient of NGAL ranged from 0.2 to 0.4 during HF and it appeared to increase with time, suggesting an initial effect of membrane adsorption. HP proved clearly that there was adsorption of NGAL by the membrane and the point of saturation occured at approximately 60 minutes from the start of circulation. Our evaluation demonstrates that NGAL can be adsorbed and ultrafiltrated with polysulfone membranes. This should be taken into consideration when using NGAL as an AKI biomarker in patients undergoing EC circulation.

Comparative study of anticoagulation versus saline flushes in continuous renal replacement therapy.

Systemic heparinization during continuous renal replacement therapy (CRRT) is associated with disadvantage of risk of bleeding. This study analyses the efficacy of frequent saline flushes compared with heparin anticoagulation to maintain filter life. From January 2004 to November 2007, 65 critically ill patients with acute renal failure underwent CRRT. Continuous venovenous hemodialfiltration (CVVHDF) was performed using Diapact Braun CRRT machine. 1.7% P.D. fluid was used as dialysate. 0.9% NS with addition of 10% Ca Gluconate, Magnesium Sulphate, Soda bicarbonate and Potassium Chloride added sequentially in separate units were used for replacement, carefully monitoring their levels. Anticoagulation of extracorporeal circuit was achieved with unfractionated heparin (250-500 units alternate hour) in 35 patients targeting aPTT of 45-55 seconds. No anticoagulation was used in 30 patients with baseline APTT > 55 seconds and extracorporeal circuit was maintained with saline flushes at 30 min interval. 65 patients including 42 males. Co-morbidities were comparable in both groups. HMARF was significantly more common in heparin group while Sepsis was comparable in both the groups. CRRT parameters were similar in both groups. Average filter life in heparin group was 26 +/- 6.4 hours while it was 24.5 +/- 6.36 hours in heparin free group (P=NS). Patients receiving heparin had 16 bleeding episodes (0.45/patient) while only four bleeding episodes occurred in heparin free group (0.13/patient, P < 0.05). Mortality was 71% in heparin group and 67% in heparin free group. Frequent saline flushes is an effective mode of maintainance of extracorporeal circuit in CRRT when aPTT is already on the higher side, with significantly decreased bleeding episodes.

Markers of inflammation and oxidative stress in peritoneal dialysis: a comparison between high and low peritoneal transporters.

INTRODUCTION: High transport status is reported to be associated with increased mortality in peritoneal dialysis (PD). It has been hypothesized that this might be a result of a state of chronic inflammation and increased oxidative stress. We performed this pilot study to explore this hypothesis. METHODS: Based on the standard peritoneal equilibration test, PD patients were divided in two transporter groups: LOW (Low + Low average) and HIGH (High + High Average). Markers of inflammation and oxidative stress were compared between the two groups, including C-reactive protein (CRP), plasma apoptogenic potential, monocyte HLA DR expression, Advanced Oxidative Protein Products (AOPP) and reactive carbonyl residues (RCO). RESULTS: Of 42 patients (34 male/8 female) studied, 8 patients were LOW and 34 were HIGH transporters. Median values of CRP (1.39 vs. 0.62 mg/L), plasma apoptogenic potential (15 vs. 14.5%), AOPP (118.36 vs. 113.86 micromol/L) and RCO (1.72 vs. 1.13 nmol/mg protein) were similar among LOW and HIGH transporters. However HIGH transporters had significantly lower monocyte HLA DR expression (mean fluorescent intensity (MFI) -197.89 vs. 124.98 units, p=0.02) compared with LOW transporters. CONCLUSIONS: Stable chronic PD patients with high peritoneal transport status have reduced monocyte HLA-DR expression, a biomarker of increased risk for infections. This could potentially contribute to a higher risk of mortality in this group.

NGAL: a biomarker of acute kidney injury and other systemic conditions.

Neutrophil gelatinase-associated lipocalin (NGAL) is a 25 kDa protein belonging to the lipocalin superfamily. It was initially found in activated neutrophils, however, many other cells, like kidney tubular cells, may produce NGAL in response to various insults. Recently, it has been found to have a role in iron metabolism by virtue of its binding with siderophores. It has also been found to have a role in kidney development and tubular regeneration after injury. In experimental studies, it was found to be highly expressed in response to tubular injury. In subsequent clinical studies, urine NGAL has been found to be an early predictor for acute kidney injury (AKI). Newer devices for early bedside detection of NGAL are now available. Since serum creatinine is known to be an inadequate and late marker of AKI, NGAL might soon emerge as a troponin-like early marker for AKI. Recent evidence also suggests its role as a biomarker in a variety of other renal and non-renal conditions.

High-resolution sonography is effective in detection of soft tissue foreign bodies: experience from a rural Indian center.

OBJECTIVE: Patients with penetrating trauma or field injuries are commonly encountered by emergency physicians. Clinical examination by inspection or palpation can detect superficial foreign bodies (FBs), and radiographs can detect radiopaque FBs. However, soft tissue FBs can be easily missed. The aim of our series was to evaluate the role of high-resolution sonography in detection of soft tissue FBs. METHODS: All patients referred to our center for sonographic evaluation of suspected soft tissue FBs from 1999 to 2008 were included in this analysis. Patients were scanned with an ultrasound machine using a 7.5-MHz transducer. The suspected area was scanned in both axial and sagittal planes. The nature of the FB, length, and depth from the surface were recorded and reported. The presence of an FB was confirmed by surgical excision. RESULTS: During the study period, 123 patients underwent sonography for a suspected FB, of which 12 were lost to follow-up and excluded from the analysis. The study group included 73.8% male patients; the mean age was 36.2 years. Wood fragments and wooden thorns were the most frequently observed FBs, at 46.2% and 36.2%, respectively. The surgeon was satisfied with the reported depth of the FB from the surface in most cases (89%). The overall sensitivity and specificity of sonography were 94.5% and 53.8%. CONCLUSIONS: High-resolution sonography is a very sensitive tool in diagnosis of soft tissue FBs. It also helps the surgeon with accurate localization, permitting easy removal.

Early diagnosis of acute kidney injury: the promise of novel biomarkers.

The incidence of acute kidney injury (AKI) formerly referred to as acute renal failure (ARF) is increasing to epidemic proportions. Development of AKI portends excessive morbidity and mortality. AKI is associated with prolonged hospital stay, increased healthcare costs and high mortality especially in critically ill patients. The mortality rate has remained largely unchanged for many decades. Delay in the diagnosis of AKI using conventional biomarkers like urine output and serum creatinine has been one of the important obstacles in applying effective early interventions. Several new biomarkers are being evaluated in a quest for early diagnosis of AKI, among which neutrophil gelatinase-associated lipocalin (NGAL) appears to be one of the most promising. This review summarizes the recent literature on these biomarkers.

Using continuous renal replacement therapy to manage patients of shock and acute renal failure.

BACKGROUND: The incidence of acute renal failure (ARF) in the hospital setting is increasing. It portends excessive morbidity and mortality and a considerable burden on hospital resources. Extracorporeal therapies show promise in the management of patients with shock and ARF. It is said that the potential of such therapy goes beyond just providing renal support. The aim of our study was to analyze the clinical setting and outcomes of critically ill ARF patients managed with continuous renal replacement therapy (CRRT). PATIENTS AND METHODS: Ours was a retrospective study of 50 patients treated between January 2004 and November 2005. These 50 patients were in clinical shock and had concomitant ARF. All of these patients underwent CVVHDF (continuous veno-venous hemodiafiltration) in the intensive care unit. For the purpose of this study, shock was defined as systolic BP < 100 mm Hg in spite of administration of one or more inotropic agents. SOFA (Sequential Organ Failure Assessment) score before initiation of dialysis support was recorded in all cases. CVVHDF was performed using the Diapact((R)) (Braun) CRRT machine. The vascular access used was as follows: femoral in 32, internal jugular in 8, arteriovenous fistula (AVF) in 4, and subclavian in 6 patients. We used 0.9% or 0.45% (half-normal) saline as a prefilter replacement, with addition of 10% calcium gluconate, magnesium sulphate, sodium bicarbonate, and potassium chloride in separate units, while maintaining careful monitoring of electrolytes. Anticoagulation of the extracorporeal circuit was achieved with systemic heparin in 26 patients; frequent saline flushes were used in the other 24 patients. RESULTS: Of the 50 patients studied, 29 were males and 21 females (1.4:1). The average age was 52.88 years (range: 20-75 years). Causes of ARF included sepsis in 24 (48%), hemodynamically mediated renal failure (HMRF) in 18 (36%), and acute over chronic kidney disease in 8 (16%) patients. The overall mortality was 74%. The average SOFA score was 14.31. The variables influencing mortality on multivariate analysis were: age [odds ratio (OR):1.65; 95% CI: 1.35 to 1.92; P = 0.04], serum creatinine (OR:1.68; 95% CI: 1.44 to 1.86; P = 0.03), and serum bicarbonate (OR: 0.76; 95% CI: 0.55 to 0.94; P = 0.01). On univariate analysis the SOFA score was found to be a useful predictor of mortality. CONCLUSIONS: Despite advances in treating critically ill patients with newer extracorporeal therapies, mortality is dismally high. Multiorgan dysfunction adversely affects outcome of CRRT. Older age, level of azotemia, and severity of metabolic acidosis are important predictors of adverse outcome.

Cardiorenal syndrome: biomarkers linking kidney damage with heart failure.

All the vital organs of the body share information by virtue of various biological mediators. Primary pathology of a major organ can lead to dysfunction of the other. Cardiorenal syndrome is an important example of such organ crosstalk. Primary dysfunction of the heart or kidney can lead to injury of the other organ. As molecular injury occurs prior to clinical dysfunction, effective interventions can be planned if one can detect this organ dysfunction at an earlier stage by virtue of some biological markers. Such biomarkers can be substances in urine, serum, imaging maneuvers or any other quantifiable parameters. Some currently available biomarkers are not sensitive enough to provide timely diagnosis of the disorder. An important research priority is the development of newer biomarkers or a panel of biomarkers for the early diagnosis of organ dysfunction, as well as nature of injury, guidance for therapeutic interventions and prognosis. Many newer biomarkers have been studied for both heart and kidney dysfunction. This article focuses on newer biomarkers for the cardiorenal syndrome.

Vitamin D dependent rickets type II: late onset of disease and response to high doses of vitamin D.

Vitamin D dependent rickets Type II is a rare autosomal recessive disorder. The disorder is characterized by end organ hyporesponsiveness to vitamin D. Common presentation of the disorder is total body alopecia and onset of rickets during the second half of the first year of life. Patients may display progressive rachitic bone changes, hypocalcemia and secondary hyper-parathyroidism. It is differentiated from vitamin D dependent rickets type I by virtue of response to physiological doses of exogenous vitamin D in the later. Target organ hyporesponsiveness can be overcome by higher doses of vitamin D or its analogues. We report a case of vitamin D dependent rickets type II with onset of rickets at the age of thirteen years without alopecia progressing to marked disability by twenty three years of age. She responded to massive doses of vitamin D with significant clinical improvement after six months of therapy.