Extracellular Volume Overload Research Articles

The kidney in congestive heart failure: ‘are natriuresis, sodium, and diuretics really the good, the bad and the ugly?’

This review discusses renal sodium handling in heart failure. Increased sodium avidity and tendency to extracellular volume overload, i.e. congestion, are hallmark features of the heart failure syndrome. Particularly in the case of concomitant renal dysfunction, the kidneys often fail to elicit potent natriuresis. Yet, assessment of renal function is generally performed by measuring serum creatinine, which has inherent limitations as a biomarker for the glomerular filtration rate (GFR). Moreover, glomerular filtration only represents part of the nephron's function. Alterations in the fractional reabsorptive rate of sodium are at least equally important in emerging therapy-refractory congestion. Indeed, renal blood flow decreases before the GFR is affected in congestive heart failure. The resulting increased filtration fraction changes Starling forces in peritubular capillaries, which drive sodium reabsorption in the proximal tubules. Congestion further stimulates this process by augmenting renal lymph flow. Consequently, fractional sodium reabsorption in the proximal tubules is significantly increased, limiting sodium delivery to the distal nephron. Orthosympathetic activation probably plays a pivotal role in those deranged intrarenal haemodynamics, which ultimately enhance diuretic resistance, stimulate neurohumoral activation with aldosterone breakthrough, and compromise the counter-regulatory function of natriuretic peptides. Recent evidence even suggests that intrinsic renal derangements might impair natriuresis early on, before clinical congestion or neurohumoral activation are evident. This represents a paradigm shift in heart failure pathophysiology, as it suggests that renal dysfunction-although not by conventional GFR measurements-is driving disease progression. In this respect, a better understanding of renal sodium handling in congestive heart failure is crucial to achieve more tailored decongestive therapy, while preserving renal function.

Interstitial fluid homeostasis and pressure: news from the black box

Extracellular volume expansion may lead to elevated blood pressure. This long-term adaptation of the vascular bed to extracellular volume overload is considered a multifactorial and not perfectly understood 'autoregulatory' event, which is difficult to measure. In this issue, Ebah and colleagues demonstrate a direct relationship between fluid overload and pressure in CKD patients. Surprise, instead of intravascular volume, interstitial fluids and pressures were measured. Finally!

The relevance of dietary sodium in hemodialysis

Since the earliest days of hemodialysis, dietary sodium restriction has been recommended as a therapeutic means to mitigate problems of extracellular volume overload, hypertension and inter-dialytic weight gain. Recently, there has been a proliferation of human subjects' research examining the potential effects of dietary sodium curtailment. Herein we examine the available evidence with respect to the effects of dietary sodium restriction on clinically relevant endpoints among hemodialysis patients.

Bioimpedance-based volume at clinical target weight is contracted in hemodialysis patients with a high body mass index

To compare volume overload in stable hemodialysis (HD) patients assessed by standard clinical judgment with data obtained from bioimpedance analysis. Ultrafiltration volume (VU) was delivered as prescribed by standard clinical practice. Independently, a measure for volume overload was assessed by a clinical score (SW). The Body Composition Monitor (BCM, Fresenius Medical Care, Bad Homburg, Germany) was used to derive values for extracellular volume (VE) and volume overload (VO) before HD. Arterial pressures (P0, P1) and serum levels of NT-pro-BNP (B0, B1) were evaluated before and after HD. In 28 patients (11 women, age: 51.3 ± 13.3 y, body mass index (BMI) 18.5 - 40.9 kg/m2; VE: 17.91 ± 3.45 l) delivered VU was 2.41 ± 1.03 l and not different from VO of 2.08 ± 1.49 l derived from bioimpedance analysis. There was no correlation between VO and VU (r = -0.15, p = 0.46) but a negative correlation between the difference VO - VU (i.e., the volume overload at treatment end) and BMI (r = -0.49, p < 0.01). Positive correlations were observed between B0 and the relative volume overload (= VO/VE) (r = 0.58, p < 0.001). The well recognized relationship between cardiac natriuretic peptides and volume expansion was confirmed. The volume overload at treatment end (VO - VU) was negligible for the whole group of patients but more negative with increasing BMI. It therefore appears that in comparison to bioimpedance-based evaluation the clinical judgment overestimates volume overload in obese patients which leads to the delivery of high ultrafiltration volumes and to volume contraction at the end of a dialysis session in this group of patients.

Plasma B-type natriuretic peptide in dialyzed patients: marker of cardiovascular disease or link to plasma refilling

B-type natriuretic peptide (BNP) is released in response to extracellular volume and blood pressure (BP) overload and is a risk factor for cardiovascular diseases (CVD). BNP is increased in dialyzed patients (HDpts). The aim of this study was to evaluate the relationships between BNP and renin, aldosterone and blood volume reduction rate (BV/WL), with the presence of CVD and mortality. Fifty-one HDpts aged 70 ± 14 years were enrolled. BP, BV/WL, BNP, aldosterone, renin, C-reactive protein (CRP), troponin I and routine biochemistry were measured. According to the predialytic plasma BNP levels, the patients were divided into group A with higher BNP and group B with lower BNP than the median value of 330 pg/mL. Follow-up was 1 year. After HD, plasma BNP (449.6 ± 582.2 pg/mL vs. 264.1 ± 269.8 pg/mL, p=0.0008) and aldosterone (421.8 ± 573.4 pg/mL vs. 265.1 ± 566.2 pg/mL, p=0.0003) decreased, but not rennin. BNP decreased more after hemodiafiltration than after standard HD (-55.1% ± 28.5% vs. -26.5% ± 19.5%, p=0.002). Patients in group A exhibited more diabetes (58% vs. 28%, p=0.03), ischemic heart disease (42% vs. 16%, p=0.04), left ventricular hypertrophy (88.8% vs. 33.3%, p<0.001), elevated levels of troponin I, CRP (50% vs. 24%, p=0.05), and low BV/BWL in a lower percentage (8% vs. 32%, p=0.03). After 11.2 ± 3.5 months, 8 patients (33.3%) had died in group A and 2 (8%) in group B (p=0.02). This study demonstrates that BNP is high in HDpts and decreases after HD. It is correlated with a good capacity for plasma refilling, with diabetes, CVD and short-term mortality risk.

Relationship Between Overnight Rostral Fluid Shift and Obstructive Sleep Apnea in Drug-Resistant Hypertension

Obstructive sleep apnea occurs frequently in patients with drug-resistant hypertension. The factors accounting for this observation, however, are unclear. Both conditions demonstrate clinical features suggestive of extracellular fluid volume overload. The aims of this study were to examine whether the spontaneous overnight fluid shift from the legs to the upper body is associated with obstructive sleep apnea in hypertensive subjects and whether its magnitude is greater in drug-resistant hypertension. Leg fluid volume and the circumference of the calf and neck were measured before and after sleep in drug-resistant hypertensive (n = 25) and controlled hypertensive (n=15) subjects undergoing overnight polysomnography. The severity of obstructive sleep apnea was greater in the drug-resistant hypertensive group than in the controlled hypertensive group (apnea-hypopnea index: 43.0 ± 5.4 versus 18.1 ± 4.2 events per hour of sleep; P = 0.02, case-mix adjusted). In both groups, the apnea-hypopnea index strongly related to the amount of leg fluid volume displaced (R² = 0.56; P < 0.0001), although the magnitude of change was greater in the drug-resistant hypertensive group (346.7 ± 24.1 versus 175.8 ± 31.3 mL; P = 0.01, propensity-score adjusted). The overnight reduction in calf circumference and increase in neck circumference were also greater in drug-resistant hypertension (both P ≤ 0.02). In hypertensive subjects, rostral fluid displacement strongly relates to the severity of obstructive sleep apnea with its magnitude being greater in drug-resistant hypertension. Our findings support the concept that fluid redistribution centrally during sleep accounts for the high prevalence of obstructive sleep apnea in drug-resistant hypertension.

Fetuin-A: A Novel Cardiovascular Risk Factor

Fetuin-A, or α2-Heremans–Schimd glycoprotein, is a potent inhibitor of calcium-phosphate precipitation. In end-stage renal disease (ESRD) patients, its serum levels are significantly reduced favouring ectopic calcifications, such as vascular and valvular calcifications for hyperphosphatemia and increased Ca × P product. Numerous evidences indicate that in low fetuin-A levels patients, mitral and/or aortic calcifications are often present. Coronary, carotid calcifications and/or other vascular phatological findings connected with increased calcium deposition in the lamina media of the arterial wall (Monkeberg’s calcinosis or arteriosclerosis), acute inflammation and/or endothelial dysfunction can be also found. Thus, low levels of fetuin-A in ESRD act as “non-traditional” risk factor for cardiovascular disease. Other “non-traditional” cardiovascular risk factors in dialyzed patients are: extracellular volume overload; insulin resistance; anaemia, and oxidative stress, many cross-sectional studies showed a direct associations of high fetuin-A levels with impaired glucose and lipid metabolism inducing metabolic syndrome in non-dialyzed patients. In these, high fetuin-A levels induce atherosclerotic lesions by insulin resistance. In conclusion, fetuin-A is able to induce both arteriosclerosis and atherosclerosis. Its serum levels seems to act (both in dialyzed and non-dialyzed patients) such as “non-traditional” cardiovascular risk factor, even if its action mechanism was not completely elucidated and further studies performed in wide range are requested. Therapeutically, some compounds such as Sevelamer, etidronate, calcium channel blockers and others interventions, are promising in to reduce calcium deposition in the vessel walls and acute inflammation induced by the low α2-Heremans–Schmid glycoprotein serum levels in dialyzed patients. On the contrary, extended-release niacin seems to be able to reduce cardiovascular, metabolic and inflammatory complicances dependent on high fetuin-A serum levels.

The growing problem of intradialytic hypertension

Intradialytic hypertension is not a rare complication of dialysis, with a prevalence of 5-15% among hemodialysis patients, and it seems to be associated with adverse outcomes. This complex phenomenon is not well understood, and many uncertainties exist regarding its pathophysiologic mechanisms and appropriate treatment strategies. Mechanisms that might be involved in the pathogenesis of intradialytic hypertension include extracellular volume overload, increased cardiac output, changes in electrolyte levels (particularly sodium), activation of the renin-angiotensin-aldosterone system, overactivity of the sympathetic nervous system, and endothelial cell dysfunction. Most current treatment strategies are based only on expert opinion and not on the results of randomized clinical trials, as very little data on the therapy of intradialytic hypertension are available. The most important treatment is adequate sodium and water removal, but reducing sympathetic hyperactivity and reducing endothelin-1 levels should also be considered. Well-designed, randomized clinical trials are urgently needed to better understand the pathophysiologic mechanisms of this complex phenomenon and to improve its diagnosis, prognosis and treatment.

Hydration Status Does Not Influence Peritoneal Equilibration Test Ultrafiltration Volumes

The peritoneal equilibration test (PET) was developed some 25 yr ago and has been used to help prescribe peritoneal dialysis. However, PET is affected by several factors, including diabetes and inflammation. It was speculated that extracellular fluid overload would increase PET ultrafiltration volumes, and therefore the usefulness of the PET in routine clinical practice was audited. Data from 211 consecutive patients attending a university teaching hospital for a standard PET who had multifrequency bioimpedance performance were analyzed to determine which factors affected net PET ultrafiltration volumes. Net PET ultrafiltration volume was independent of gender, age, diabetes, residual renal function, peritoneal dialysis prescriptions (modes and dialysates), extracellular fluid volume, or C-reactive protein (CRP). There was an inverse regression with serum albumin and sodium on multiple logistical regression analysis (F = 13.4, P < 0.001 and F = 10.1, P = 0.001, respectively) and a positive regression with 24-h net peritoneal ultrafiltration volumes (F = 15.5, P < 0.001). As expected, there was a strong correlation with net sodium losses (r = 0.99, P < 0001). It was found that PET test ultrafiltration volume in routine clinical practice was not affected by CRP, hyperglycemia, or extracellular fluid volume overload. Ultrafiltration volumes were increased in those patients with reduced serum sodium and albumin, most likely because of inflammation and protein malnutrition.

Hypertension in Hemodialysis. An Overview on Physiopathology and Therapeutic Approach in Adults and Children

Chronic Kidney disease (CKD) patients, particularly those with end stage renal disease (ESRD), are at much higher risk of cardiovascular disease than the general population. Cardiovascular disease is by far the leading cause of morbidity and mortality in dyalisis patients, accounting for almost 40% of hospitalizations and almost 50% of deaths. Hypertension is the single most important factor for the development of cardio and cerebrovascular complications. The etio-pathogenesis of hypertension in dialysis patients is multifactorial, sodium excess and extracellular volume expansion is the major factor in the development of hypertension, however there are other pathogenetic factors that should be con- sidered, such as renin-angiotensin system hyperactivity, increased sympatic activity, altered endothelial cell function, hy- perparathiroidism, and oxidative stress. The most important risk factors are anemia, hypoalbuminemia, chronic inflamma- tion, prothrombotic factors, hyperomocisteinemia, vascular calcification and the traditional factors for cardiovascular risk (age, male gender, diabetes mellitus, dyslipidemia, smoke, physical inactivity, alcohol abuse). Elevated blood pressure is frequent also in children on long term dialysis therapy. Data suggest that uremic factors or fac- tors related to renal replacement therapy may be implicated in the pathogenesis of heart disease in adults and pediatric pa- tients, because cardiovascular survival improves after transplantation. The management of hypertension requires lifestyle modifications and control of volume status, with dietary salt and fluid restriction in combination with reduction of dialysate sodium concentration or with programmed variable-sodium dialy- sis. The relationship between interdialytic weight and blood pressure is incompletely characterized; the dry weight (DW) method relies on the progressive reduction of the postdialysis body weight until blood pressure is normalized. There are several non clinical methods for evaluation DW such as measure the inferior vena cava diameter whit ultrasound, measure blood volume (BV) whit radiolabeled albumin and calculating post-hemodialysis BV from the change in hematocrit. It may exist a lag time of several weeks between the normalization of the extracellular volume and blood pressure. It is re- lated to the correction of the hemodinamic consequences of the extracellular volume overload. The other problems to limit the possibility of correcting adequately volume expansion with dialysis are the use of anti- hypertensive drugs and the aggressive ultrafiltration required by short dialysis times. A possible treatment option for these patients may be increase time hemodialysis with slow, long hemodialysis; short, daily hemodialysis or nocturnal hemo- dialysis. All classes of antihypertensive drugs can be used in dialysis patients, except the diuretics because inefficacy. Angiotensin- converting enzyme (ACE) and Angiotensin T1 receptor antagonist (AT1RA) appear to have the greatest ability to reduce left ventricular mass.

Kinetic Analysis of Peritoneal Fluid and Solute Transport with Combination of Glucose and Icodextrin as Osmotic Agents

Controlling extracellular volume and plasma sodium concentration are two crucial objectives of dialysis therapy, as inadequate sodium and fluid removal by dialysis may result in extracellular volume overload, hypertension, and increased cardiovascular morbidity and mortality in end-stage renal disease patients. A new concept to enhance sodium and fluid removal during peritoneal dialysis (PD) is the use of dialysis solutions with two different osmotic agents. To investigate and compare, with the help of mathematical modeling and computer simulations, fluid and solute transport during PD with conventional dialysis fluids (3.86% glucose and 7.5% icodextrin; both with standard sodium concentration) and a new combination fluid with both icodextrin and glucose (CIG; 2.6% glucose/6.8% icodextrin; low sodium concentration). In particular, this paper is devoted to improving mathematical modeling based on critical appraisal of the ability of the original three-pore model to reproduce clinical data and check its validity across different types of osmotic agents. Theoretical investigations of possible causes of the improved fluid and sodium removal during PD with the combination solution (CIG) were carried out using the three-pore model. The results of computer simulations were compared with clinical data from dwell studies in 7 PD patients. To fit the model to the low net ultrafiltration (366+/-234 mL) obtained after a 4-hour dwell with 3.86% glucose, some of the original parameters proposed in the three-pore model (Rippe & Levin. Kidney Int 2000; 57:2546-56) had to be modified. In particular, the aquaporin-mediated fractional contribution to hydraulic permeability was decreased by 25% and small pore radius increased by 18%. The simulations described well clinical data that showed a dramatic increase in ultrafiltration and sodium removal with the CIG fluid in comparison with the two other dialysis fluids. However, to adapt the three-pore model to the selected group of PD patients (fast transporters with small ultrafiltration capacity on average), the peritoneal pore structure had to be modified. As the mathematical model was capable of reproducing the clinical data, this shows that the enhanced ultrafiltration with the combination fluid is caused by the additive effect of the two different osmotic agents and not by a specific impact of the new dialysis fluid on the transport characteristics of the peritoneum.

La physiopathologie de l’hypertension artérielle en dialyse chronique

Hypertension in subjects on long term dialysis is frequent. Its origins are found in extracellular volume overload, which is complicated by increased peripheral arterial resistance. The latter is affected by many systems, including that of renin-angiotensin, endothelin, nitric oxide, the sympathetic nervous system, and others. The interaction between these factors may explain why the control of hypertension in dialysis patients requires ongoing attention to the many aspects of good dialysis.

Traitement non médicamenteux de l’hypertension artérielle en hémodialyse

High blood pressure in dialysis patients is related to extracellular volume excess and the related increase of systemic vascular resistances. Scribner has early described the treatment of hypertension with ultrafiltration and low salt diet, without any drugs. The dry weight method relies on the progressive reduction of the postdialysis body weight until blood pressure is normalized. Additional measures are needed such as low salt diet, neutral sodium balance during dialysis treatment, stop of antihypertensive drugs, adequate length of the dialysis session, and patient education. It may exist a lag time between the normalizations of the extracellular volume and blood pressure. It is related to the correction of the hemodynamic consequences of the extracellular volume overload. Moreover, the dry weight may potentially vary in patients undergoing catabolic intercurrent events. The complications of these changes (severe hypertension, pulmonary oedema) must be anticipated by the nephrologist and the staff to avoid additional morbidity to the patient.

Cardiovascular Risk Factors in Peritoneal Dialysis Patients Revisited

End-stage renal disease patients are at a heightened risk of developing cardiovascular disease, with contributions from both "traditional" and "nontraditional" cardiovascular risk factors. Some of the nontraditional risk factors, such as extracellular volume overload, inflammation, and hyperphosphatemia, have also been shown to be important predictors of mortality in the dialysis population. This article provides an in-depth review of the evidence that supports the substantial contributions of nontraditional risk factors to adverse cardiovascular outcomes in chronic peritoneal dialysis patients. In addition, it provides evidence to demonstrate how loss of residual renal function may be central to the development of cardiovascular disease in the peritoneal dialysis population.

Ichthyotoxic ARF after fish gallbladder ingestion: a large case series from Vietnam

Fish gallbladders are consumed in rural areas of Asia as a traditional medicine to improve symptoms of arthritis, decreased visual acuity, and impotence. Consumption of large amounts of this traditional medicine can result in systemic toxicities; in particular, acute renal failure. We reviewed records of all admissions to Cho Ray Hospital (Ho Chi Minh City, Vietnam) between January 1995 and December 2000 after this ingestion. Clinical courses and outcomes were similar in 16 of 17 patients. Within hours, patients experienced profuse vomiting (n = 16) and diarrhea (n = 15). All developed acute renal failure, with a mean serum creatinine concentration of 14.7 ± 3.9 mg/dL (1,299.5 ± 344.8 μmol/L). Four patients administered intravenous fluid (IVF) developed extracellular fluid volume overload, as did 1 patient not administered IVF. Time to peak creatinine concentration was 8.6 ± 3.0 days, which was accompanied by decreased urine volume (174.7 ± 161.6 mL/24 h). Blood pressure remained normal, with a mean arterial pressure of 91 ± 12 mm Hg. Twelve patients required renal replacement therapy. A mean of 1.9 ± 1.1 hemodialysis sessions was performed per patient. Sixteen patients recovered renal function; 1 patient died of fulminant hepatic failure. Kidney biopsies showed features of acute tubular injury. Acute renal failure after fish gallbladder ingestion is characterized by a failure to respond to IVF, an 8.6-day interval to peak creatinine level, frequent need for dialysis therapy, and findings on renal biopsy consistent with acute tubular necrosis. Acute renal failure after fish gallbladder ingestion has an excellent prognosis. However, death from fulminant hepatic failure can occur. Am J Kidney Dis 41:220-224. © 2003 by the National Kidney Foundation, Inc.

Blood Pressure Is Correlated with Vitamin D3 Serum Levels in Dialysis Patients

Background/Aim: The blood pressure, the most influencing factor in cardiovascular disease in end-stage renal failure patients, follows a seasonal variation during the year. Since vitamin D₃ is known to be related to sun exposure, we wanted to evaluate the putative participation of the vitamin D₃ metabolism in blood pressure modifications. Methods: We studied 22 stable hemodialysis patients (11 females and 11 males, mean age ± SD 56 ± 1 year) who had been continuously treated in our dialysis unit for more than 1 year between 1994 and 1997 and did not receive pulse vitamin D₃ treatment. Supine systolic and diastolic blood pressures were measured before every dialysis session (>12,000 measurements) and the intact parathormone (iPTH), 25-hydroxyvitamin D₃ [25(OH)D₃], and 1,25-dihydroxyvitamin D₃ [1,25(OH)₂D₃] levels every 3 months (>300 determinations). The mean values of blood pressure per season and per patient were taken for analysis using a 4-year longitudinal study design. Results: The blood pressure varied during the years studied following a seasonal trend. It was highest during autumn and tended to decrease during spring and warmer months. Systolic as well as diastolic blood pressures were significantly correlated with the 25(OH)D₃ levels (p = 0.0291 and p = 0.0327, respectively). No correlation was observed between blood pressure and 1,25(OH)₂D₃ or iPTH levels. Conclusions: There is a link between blood pressure and 25(OH)D₃ level. This interrelation is not secondary to a iPTH modulation. Although it cannot be excluded that vitamin D₃ and blood pressure vary following a third factor with seasonal variations, since vitamin D₃ varies during the year, mainly following sun exposure, we suggest that vitamin D₃ is one of the factors participating in the seasonal variation of the blood pressure. Other factors known to control the blood pressure and particularly the extracellular volume overload may also participate.

Metabolic abnormalities in acute renal failure, influence on nutritional management

Acute renal failure (ARF) occurs when there is a rapid loss of the clearance capacity of the kidney. This leads to an abrupt accumulation of unexcreted waste products. Even though the specificity of uremic toxins is debated, it is clear that accumulated waste products lead to anorexia, lethargy, nausea, vomiting and other symptoms associated with uremia. ARF also causes accumulation of sodium, water and electrolytes which can cause life threatening problems from extracellular volume overload, hyperkalemia, etc.

Metabolic Alkalosis

Metabolic alkalosis is a common acid-base disturbance in critically ill patients. In this review we discuss the approach to diagnosis and management of this disorder; particular emphasis is given to the causes most com monly responsible for alkalosis in critical care medicine. We present rules for (1) identifying the presence of metabolic alkalosis, ( 2 ) determining whether the disor der is simple or complicated by a second acid-base dis turbance, and (3) determining the cause: The causes are subdivided into three major groups: Chloride-respon sive, chloride-resistant, and alkali administration. The pathogenesis of each type of alkalosis is discussed sep arately, although we stress that more than one cause may be responsible in critically ill patients. The patho logical consequences of metabolic alkalosis and ap proaches to treatment are reviewed. The major issues relating to the critically ill patient are (1) identification and removal of exogenous sources of alkali, (2) iden tification and minimization of HCl losses or selective NaCl losses, and (3) maneuvers to reduce serum HCO 3 concentration without producing extracellular fluid volume overload.

Coronary-artery surgery in patients with end-stage renal disease.

Between 1975 and 1979 we performed coronary arteriography on 15 patients with end-stage renal failure and clinical evidence of severe ischemic heart disease. One patient died after the procedure of severe pump failure. Ten patients subsequently received coronary-artery bypass grafts, and two of these patients also received mitral-valve replacement. One patient, a diabetic, died of sepsis after surgery. Eight of the nine surviving patients, including the two patients who had undergone mitral-valve replacement, are markedly improved as a result of surgery. Our experience indicates that these patients can undergo angiography and coronary-artery bypass surgery at an increased but acceptable risk, provided dialysis is done before and after cardiac catheterization and surgery to control extracellular volume overload and hyperkalemia. The operation benefits patients with end-stage renal failure and severe ischemic heart disease by relieving angina and improving their level of activity. It is unclear whether survival is improved for these patients.

Management of acute renal failure in infants and children.

The definition, causes and management of acute renal failure in children are described. This includes treatment of both specific and nonspecific problems. The specific problems include hyperkalemia, acidosis, sodium control, hypocalcemia, extracellular volume overload, hypertension, seizures and anemia. Supportive treatment is also considered including continuing assessment of the patient’s status, water and calorie requirements, central venous pressure measurements and transport of patients! The indications for peritoneal dialysis are described and also the technique and possible complications.