Can increased vigilance for chronic kidney disease in hospitalised patients decrease late referral and improve dialysis-free survival?

BACKGROUND: Insufficient vigilance for renal insufficiency is associated with late referral, increased morbidity and mortality. The present study examines whether increased vigilance for chronic kidney disease (CKD) leads to quicker referral to and better follow-up by a nephrologist, and whether it is associated with an improved outcome. METHODS: Patients with an eGFR < 45 ml/min/1.73 m2 during hospitalisation at the Ghent University Hospital were enrolled during a period of 100 days. The patients were interviewed about their awareness of CKD. Both the patients and their general practitioner were subsequently informed about CKD. The primary endpoint was the number of patients referred for nephrological follow-up within three months. The secondary endpoint was need for dialysis and mortality from any cause one year after inclusion. RESULTS: Of the 72 included patients, 54 had proven CKD, with eGFR consistently < 45 ml/min/1.73 m2 during at least three months before inclusion. Merely 65% was aware of having CKD and only 41% was in regular nephrological follow-up. After intervention, the percentage of patients with CKD in follow-up increased from 41% to 71% (p = 0.002). The proportion reaching the secondary endpoint was significant lower in the patients who were referred quickly than in those who were not (p = 0.015). Similarly, the proportion was significant lower in the patients who received nephrological follow-up than in those who did not (p = 0.006). CONCLUSION: Vigilance for CKD is poor. Simple interventions to augment the vigilance for CKD, as presented in this study, lead to a quicker referral to and follow-up by a nephrologist, which may result in better outcome.

The paradox of bardoxolone methyl: a call for every witness on the stand?

People with type 2 diabetes and chronic kidney disease (CKD) remain an extremely vulnerable population with increased cardiovascular morbidity, mortality and mounting societal costs. As such, any effort to improve their dismal outcome is heavily supported. Yet, most drugs fail to replicate the promising signals of early experiments in humans in large and methodologically sound trials. As a recent example, an independent data and safety committee advised the termination of a phase 3 trial due to excessive cardiovascular disease and especially heart failure in patients allocated to the antioxidant synthetic triterpenoid bardoxolone methyl versus placebo. We evaluate the reasons why this outcome in hindsight was possibly not totally unexpected and develop a mechanistic model that shows that the consistent drop in serum magnesium concentration in patients exposed to bardoxolone methyl might have contributed to the development of heart failure. As such, this trial, despite its negative outcome, might provide additional pieces of the puzzle enabling us to get a better grip on diseases that share increased inflammation and oxidative stress, such as type 2 diabetes, metabolic syndrome, heart failure and CKD.

Diagnosing COVID-19; towards a feasible COVID-19 rule-out protocol.

INTRODUCTION: We present the results of the COVID-19 rule-out protocol at Ghent University Hospital, a step-wise testing approach which included repeat NFS SARS-CoV-2 rRT-PCR, respiratory multiplex RT-PCR, low-dose chest CT and bronchoscopy with BAL to confirm or rule-out SARS-CoV-2 infection in patients admitted with symptoms suggestive of COVID-19. RESULTS: Between 19 March 2020 and 30 April 2020, 455 non-critically ill patients with symptoms suspect for COVID-19 were admitted. The initial NFS for SARS-CoV-2 rRT-PCR yielded 66.9%, the second NFS 25.4% and bronchoscopy with BAL 5.9% of total COVID-19 diagnoses. In the BAL fluid, other respiratory pathogens were detected in 65% (13/20) of the COVID-19 negative patients and only in 1/7 COVID-19 positive patients. Retrospective antibody testing at the time around BAL sampling showed a positive IgA or IgG in 42.9 % of the COVID-19 positive and 10.5% of the COVID-19 negative group. Follow-up serology showed 100% COVID-19 positivity in the COVID-19 positive group and 100% IgG negativity in the COVID-19 negative group. CONCLUSION: In our experience, bronchoscopy with BAL can have an added value to rule-in or rule-out COVID-19 in patients with clinical and radiographical high-likelihood of COVID-19 and repeated negative NFS testing. Furthermore, culture and respiratory multiplex PCR on BAL fluid can aid to identify alternative microbial etiological agents in this group. Retrospective analysis of antibody development in this selected group of patients suggests that the implementation of serological assays in the routine testing protocol will decrease the need for invasive procedures like bronchoscopy.

Advantages of new hemodialysis membranes and equipment.

Chronic kidney disease is characterized by the progressive retention of a number of compounds, several of which have the potential to cause cardiovascular damage. Many of these are difficult to remove by standard dialysis strategies. Removal of the larger middle molecules (mostly larger peptidic compounds) can be obtained by increasing dialyzer pore size and/or by applying convective strategies. For protein-bound solutes, convection (essentially hemodiafiltration) positively affects removal. The HEMO study demonstrated outcome superiority for the large-pore high-flux hemodialysis membranes in a number of subgroup analyses. Likewise, the Membrane Permeability Outcome study showed outcome superiority for high flux in patients with serum albumin <4 g/dl, the group for which the study had originally been designed. Apart from a small controlled trial, data suggesting superiority for convective strategies are all observational.

Posttransplantation hypomagnesemia and its relation with immunosuppression as predictors of new-onset diabetes after transplantation.

New-onset diabetes after transplantation (NODAT) is a frequent complication and has an impact on patient and graft survival. Hypomagnesemia is common in both renal transplant recipients and in diabetics. This study examines the relationship between hypomagnesemia, NODAT and the type of immunosuppression in renal transplant recipients. We conducted a retrospective single-center analysis (2002-2008) in order to assess NODAT the first year posttransplantation as defined by American Diabetes Association criteria. Serum magnesium (Mg) levels were defined as the median of all Mg levels registered during the first month posttransplantation. Patients with NODAT (N = 75; 29.5%) versus non-NODAT had lower Mg levels (p < 0.001). Patients with an Mg level < versus > or = 1.9 mg/dL showed a faster development of NODAT (log-rank p < 0.001). Mg levels were lower in patients on calcineurin inhibitors (CNI) versus no CNI patients (p < 0.001). Mg levels, albumin, BMI, triglycerides, posttransplantation hyperglycemia, tacrolimus levels and the use of sirolimus were predictors of NODAT in the multivariate analysis. Hypomagnesemia was an independent predictor of NODAT in renal transplant recipients. We confirm that the use of CNI is associated with NODAT, but, to a large extent, this effect seems attributable to the induction of hypomagnesemia. After adjustment for Mg, sirolimus was also associated with NODAT.

Treating potassium disturbances: kill the killers but avoid overkill.

OBJECTIVES: In this publication, we review the definitions, symptoms, causes, differential diagnoses and therapies of hypokalemia and hyperkalemia. METHODS: Comprehensive tables and diagnostic algorithms are provided when appropriate. RESULTS AND CONCLUSIONS: Although both hypokalemia and hyperkalemia may be life-threatening, this is essentially the case with severe changes (serum potassium < 2.5 or > 6.5 mmol/L), the presence of symptoms or electrocardiographic deviations, the association with aggravating factors (e.g. digitalis intake) and/or rapid acute changes. Only these truly need an emergency therapeutic approach. In all other cases, a careful consideration of the causes and their correction should prevail over additional approaches to modify serum potassium concentration. Although most therapeutic approaches to both hypokalemia and hyperkalemia have been well established since many years, recently two new intestinal potassium binders have been introduced on the market. It remains to be elucidated whether these drugs truly have an additional role on top of the existing treatments.

Impact of hemodialysis duration on the removal of uremic retention solutes.

Several studies have stressed the importance of dialysis time in the removal of uremic retention solutes. To further investigate this, nine stable chronic hemodialysis patients were dialyzed for 4, 6, or 8 h processing the same total blood and dialysate volume by the Genius system and high-flux FX80 dialyzers. Inlet blood and outlet dialysate were analyzed for urea, creatinine, phosphorus, and beta2-microglobulin at various times. Total solute removal, dialyzer extraction ratios, and total cleared volumes were significantly larger during prolonged dialysis for urea, creatinine, phosphorus, and beta2-microglobulin. Reduction ratios increased progressively, except for phosphate and beta2-microglobulin, where the ratios remained constant after 2 h. In contrast, no significant difference was found for the reduction ratios of all solutes and Kt/V(urea) between the three different sessions. With longer dialyses, solutes are efficiently removed from the deeper compartments of the patient's body. Our study shows that care must be taken when using Kt/Vurea or reduction ratios as the only parameters to quantify dialysis adequacy.

Compliance with a structured bedside handover protocol: An observational, multicentred study.

BACKGROUND: Bedside handover is the delivery of the nurse-to-nurse shift handover at the patient's bedside. The method is increasingly used in nursing, but the evidence concerning the implementation process and compliance to the method is limited. OBJECTIVES: To determine the compliance with a structured bedside handover protocol following ISBARR and if there were differences in compliance between wards. DESIGN: A multicentred observational study with unannounced and non-participatory observations (n = 638) one month after the implementation of a structured bedside handover protocol. SETTINGS AND PARTICIPANTS: Observations of individual patient handovers between nurses from the morning shift and the afternoon shift in 12 nursing wards in seven hospitals in Flanders, Belgium. METHODS: A tailored and structured bedside handover protocol following ISBARR was developed, and nurses were trained accordingly. One month after implementation, a minimum of 50 observations were performed with a checklist, in each participating ward. To enhance reliability, 20% of the observations were conducted by two researchers, and inter-rater agreement was calculated. Data were analysed using descriptive statistics, one-way ANOVAs and multilevel analysis. RESULTS: Average compliance rates to the structured content protocol during bedside handovers were high (83.63%; SD 11.44%), and length of stay, the type of ward and the nursing care model were influencing contextual factors. Items that were most often omitted included identification of the patient (46.27%), the introduction of nurses (36.51%), hand hygiene (35.89%), actively involving the patient (34.44%), and using the call light (21.37%). Items concerning the exchange of clinical information (e.g., test results, reason for admittance, diagnoses) were omitted less (8.09%-1.45%). Absence of the patients (27.29%) and staffing issues (26.70%) accounted for more than half of the non-executed bedside handovers. On average, a bedside handover took 146 s per patient. CONCLUSIONS: When the bedside handover was delivered, compliance to the structured content was high, indicating that the execution of a bedside handover is a feasible step for nurses. The compliance rate was influenced by the patient's length of stay, the nursing care model and the type of ward, but their influence was limited. Future implementation projects on bedside handover should focus sufficiently on standard hospital procedures and patient involvement. According to the nurses, there was however a high number of situations where bedside handovers could not be delivered, perhaps indicating a reluctance in practice to use bedside handovers.

Development and validation of an ultra-high performance liquid chromatography-tandem mass spectrometry method to measure creatinine in human urine.

Despite decades of creatinine measurement in biological fluids using a large variety of analytical methods, an accurate determination of this compound remains challenging. Especially with the novel trend to assess biomarkers on large sample sets preserved in biobanks, a simple and fast method that could cope with both a high sample throughput and a low volume of sample is still of interest. In answer to these challenges, a fast and accurate ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method was developed to measure creatinine in small volumes of human urine. In this method, urine samples are simply diluted with a basic mobile phase and injected directly under positive electrospray ionization (ESI) conditions, without further purification steps. The combination of an important diluting factor (10(4) times) due to the use of a very sensitive triple quadrupole mass spectrometer (XEVO TQ) and the addition of creatinine-d3 as internal standard completely eliminates matrix effects coming from the urine. The method was validated in-house in 2012 according to the EMA guideline on bioanalytical method validation using Certified Reference samples from the German External Quality Assessment Scheme (G-Equas) proficiency test. All obtained results for accuracy and recovery are within the authorized tolerance ranges defined by G-Equas. The method is linear between 0 and 5 g/L, with LOD and LOQ of 5 × 10(-3) g/L and 10(-2) g/L, respectively. The repeatability (CV(r) = 1.03-2.07%) and intra-laboratory reproducibility (CV(RW) = 1.97-2.40%) satisfy the EMA 2012 guideline. The validated method was firstly applied to perform the German G-Equas proficiency test rounds 51 and 53, in 2013 and 2014, respectively. The obtained results were again all within the accepted tolerance ranges and very close to the reference values defined by the organizers of the proficiency test scheme, demonstrating an excellent accuracy of the developed method. The method was finally applied to measure the creatinine concentration in 210 urine samples, coming from 190 patients with a chronic kidney disease (CKD) and 20 healthy subjects. The obtained creatinine concentrations (ranging from 0.12 g/L up to 3.84 g/L) were compared, by means of a Passing Bablok regression, with the creatinine contents obtained for the same samples measured using a traditional compensated Jaffé method. The UHPLC-MS/MS method described in this paper can be used to normalize the concentration of biomarkers in urine for the extent of dilution.

Peritoneal dialysis favorably influences early graft function after renal transplantation compared to hemodialysis.

BACKGROUND: Delayed graft function (DGF) and acute renal failure (ARF) after renal transplantation negatively influence short- and long-term graft outcome. Peritoneal dialysis as pretransplantation dialysis modality was reported to influence favorably the recovery of renal function immediately after kidney transplantation. It has been hypothesized that fluid status was the factor explaining this better outcome. This hypothesis was tested in this study by multivariate analysis, also including other factors related to DGF and ARF. METHODS: The records of peritoneal dialysis (PD; n=40) and hemodialysis (HD; n=79) patients receiving a first cadaveric kidney transplantation at the University Hospital Gent were analyzed. RESULTS: DGF and ARF were observed in 33 (27 HD and 6 PD, P=0.03) and 14 (14 HD and 0 PD, P=0.01) patients, respectively. The number of days needed to reach a serum creatinine 50% below that before transplantation (T1/2(SCr)), was correlated with cold ischemia time (CIT) (P<0.001) and body weight gain (BWG) (P<0.01) and was inversely correlated with urinary output in the first 24 hr (P<0.001), fluid load (P<0.001), and central venous pressure (P<0.001). A multivariate model with CIT (P<0.001), PD as pretransplantation dialysis mode (P=0.01), urinary output in the first 24 hr (P=0.001), BWG (P=0.05), and fluid load (P=0.01) resulted in an R2 of 0.32 (P<0.001). Using Cox regression analysis, the relative risk for a prolonged T1/2(SCr) increased with 4%/hr CIT (P=0.01) and with 1%/kg BWG (P=0.02). Fluid load decreased the relative risk with 5%/liter (P<0.001) and PD as pretransplantation modality favorably modified the relative risk by a factor of 1.6 (P=0.01). CONCLUSION: PD as pretransplantation dialysis modality can reduce the incidence and the severity of delayed recovery of renal function after renal transplantation. This protective effect was independent from CIT, and fluid status, two other major influencing factors.

The removal of uremic toxins.

Three major groups of uremic solutes can be characterized: the small water-soluble compounds, the middle molecules, and the protein-bound compounds. Whereas small water-soluble compounds are quite easily removed by conventional hemodialysis, this is not the case for many other molecules with different physicochemical characteristics. Continuous ambulatory peritoneal dialysis (CAPD) is often characterized by better removal of those compounds. Urea and creatinine are small water-soluble compounds and the most current markers of retention and removal, but they do not exert much toxicity. This is also the case for many other small water-soluble compounds. Removal pattern by dialysis of urea and creatinine is markedly different from that of many other uremic solutes with proven toxicity. Whereas middle molecules are removed better by dialyzers containing membranes with a larger pore size, it is not clear whether this removal is sufficient to prevent the related complications. Larger pore size has virtually no effect on the removal of protein-bound toxins. Therefore, at present, the current dialytic methods do not offer many possibilities to remove protein-bound compounds. Nutritional and environmental factors as well as the residual renal function may influence the concentration of uremic toxins in the body fluids.

Gastric emptying of solids in cirrhotic and peritoneal dialysis patients: influence of peritoneal volume load.

INTRODUCTION: A delay in gastric emptying rate has been reported in peritoneal dialysis patients, often normalizing after evacuation of the dialysate. To evaluate the effect of the intraperitoneal volume, we compared this finding with a cirrhotic model in which gastric emptying was studied before and after a large-volume paracentesis. METHODS AND DESIGN: We used the 13C-octanoic acid breath test to measure gastric half-emptying time (T1/2) for solids in patients with alcoholic cirrhosis, non-diabetic peritoneal dialysis patients, and a control population (asymptomatic volunteers). Cirrhotic patients underwent the test on two consecutive mornings before and after an evacuating paracentesis. Peritoneal dialysis patients were studied twice on consecutive days: once with the dialysate present intra-abdominally ("full"), and once with an emptied abdomen ("empty"). Biochemical analysis was carried out on blood samples before the first test. All cirrhotics underwent a 13C-aminopyrine breath test to assess residual liver function. RESULTS: Gastric emptying in cirrhotics showed no difference before or after paracentesis (median T1/2 108.0 min v. 117.9 min), but it was delayed significantly versus normal in both tests. There was no correlation with biochemical parameters, Child-Pugh score, or 13C-aminopyrine breath test results. Gastric half-emptying times of "full" peritoneal dialysis patients (median T1/2 103.1 min) were significantly higher than those of "empty" peritoneal dialysis patients (median T1/2 68.9 min) and asymptomatic volunteers (median T1/2 60.1 min). "Empty" peritoneal dialysis patients showed no gastroparesis. CONCLUSION: In alcoholic cirrhotic patients with ascites, gastric emptying of solids is delayed, independently of the volume of ascites. In peritoneal dialysis patients, gastric emptying was delayed when "full" and normalized after drainage of the dialysate.

Importance of blood pressure and volume control in peritoneal dialysis patients.

OBJECTIVES: To review the factors that impact control of blood pressure and euvolemia in peritoneal dialysis patients. DESIGN: Review of the most recent publications on this subject; inclusion of some personal data on the relation between plasma volume and evolution of blood pressure in short-term and long-term peritoneal dialysis patients. SETTING: Peritoneal dialysis program in a university hospital. RESULTS: The literature on circadian blood pressure and the role of the decreased compliance of the great vessels in uremia is reviewed. Analysis of the long-term evolution of plasma volume in peritoneal dialysis patients in correlation with the evolution of blood pressure indicates a positive correlation in 36 of 46 simultaneous determinations. The treatment of volume overload and hypertension in peritoneal dialysis includes the prescription of loop diuretics, preservation of residual renal function, reduction of dietary salt intake, and prevention and treatment of peritoneal ultrafiltration failure. CONCLUSIONS: A reduction in the great cardiovascular mortality in peritoneal dialysis patients as nowadays observed can only be expected when more attention is paid to better control of hypervolemia and hypertension in these patients.

The role of peritoneal dialysis as the first-line renal replacement modality.

Twenty years after its introduction, peritoneal dialysis (PD) is a well-established alternative to hemodialysis (HD) as a modality of renal replacement therapy. Much debate and research is apparent in the literature, comparing hemodialysis and PD as "opposite" modalities and trying to ascertain which modality should be more optimal. In our opinion, HD and PD are two distinct modalities, each with its own advantages and disadvantages. In addition, it is clear that for both HD and PD, rates of technique failure are high, causing patients to transfer between modalities. The question is thus not which modality is best, but rather, which flow-chart of modalities makes best use of the advantages of each modality, while avoiding its disadvantages. In this respect, HD and PD appear to be complementary modalities. The better preservation of residual renal function, lower risk of infection with hepatitis B and C, better outcome after transplantation, preservation of vascular access, and lower costs are arguments to promote PD as a good initial treatment. When PD-related problems arise (adequacy, ultrafiltration, peritonitis, patient burnout), a timely transfer to HD has to be planned. This editorial tries to review arguments supporting the complementary nature of both modalities, and especially the role of PD as the first-line renal replacement therapy.

Integrated care.

The integrated care model for delivering RRT offers apparent advantages in patient choice, optimal survival, and economical use of resources. Dialysis and transplantation have always been used that way; but, by integrating all three treatments--HD, PD, and transplantation--the options for the multi-professional team and the patients are increased. The practical implications of the approach include the need for all treatments to be available, for patients and professionals to be educated in the approach, and for a change in therapy to be anticipated and accepted, not seen as a mark of treatment failure. Prospective studies are needed to quantify the benefits in a more systematic way.

The need for a center-tailored treatment protocol for peritonitis.

OBJECTIVE: Despite many improvements in connectology, peritonitis continues to be a major burden in peritoneal dialysis. Because of the high variety in causative organisms and of the differences in their sensitivity patterns, surveillance of the epidemiology of peritonitis and the appropriate adaptation of the therapy are necessary. This study was performed to evaluate the influence of the nature of causative bacteria on the effectiveness of empirical treatment protocols. Based on this information, a new empiric treatment protocol was proposed. SETTING: Peritoneal dialysis program of a university hospital. DESIGN: All episodes of peritonitis at the University Hospital Gent between 1 January 1994 and 31 December 1996 were analyzed retrospectively. Results of microbiological cultures, microscopic evaluation of dialysate, and clinical course were noted. RESULTS: During 1240 patient-months at risk, 50 episodes of peritonitis with identifiable responsible bacteria were observed. Gram-positive organisms were cultured in 34 episodes, and gram-negative organisms were found in 16 episodes. No responsible organism could be identified in 25 additional cases. Resistance to methicillin was registered in 33% of the cultures with staphylococci. There was no resistance to vancomycin. A new empirical treatment protocol was proposed, using a single dose of vancomycin and gentamicin intraperitoneally the first day, followed by oral treatment with ciprofloxacin. With this protocol, a 96% coverage rate is obtained, as opposed to a 78% coverage by using the Ad Hoc Advisory Committee protocol (p < 0.01). CONCLUSION: Individual centers should continue to monitor the epidemiology of peritoneal dialysis-related peritonitis and the epidemiology of the causative organisms and their sensitivity patterns in order to adapt general guidelines into a center-tailored empirical treatment protocol.

Analysis of the reasons for transfers between hemodialysis and peritoneal dialysis and their effect on survivals.

Data on the outcomes of patients who are transferred between hemodialysis (HD) and peritoneal dialysis (PD) are scant. This study analyzes data on patients transferred from their initial modality at the University Hospital Gent between 1978 and 1996 for the reasons for, and outcomes from, the transfer. The reasons for the transfer from HD to PD (n = 35) were access problems (25%), cardiovascular (40%) and blood pressure problems (25%), and personal choice (10%). For the transfer from PD to HD (n = 32) peritonitis (50%), social problems (14%), adequacy or ultrafiltration problems (25%), and leakage (11%) were the reasons. There were no differences in survivals between patients who started on HD and who were transferred to PD, and those who remained on HD (P = 0.4). There were improved survivals for the patients who started on PD and who were transferred to HD compared to those remaining on PD (P = 0.01). It is concluded that transferring problematic HD patients to PD does not improve their survivals, whereas the survival of patients with PD-related complications is improved by transferring them to HD. This is due to the differences in the reasons for transfer, which are PD-related complications in the case of PD patients, and cardiovascular problems in the case of HD patients.

Bed-side blind insertion of peritoneal dialysis catheters.

Access to the peritoneal cavity is an essential factor for successful peritoneal dialysis. The technique of catheter insertion can influence technique success and patient satisfaction. As compared to conventional surgical laparotomy, a bedside blind insertion technique under local anaesthesia has logistical advantages for the patient, the hospital and the community. This study compares outcomes of both methods in a single centre. A retrograde analysis of a prospectively collected database on all catheters implanted at the University hospital Ghent between 1/1/1998 and 31/5/2002 was carried out. During this period, catheters were implanted either by conventional laparotomy (CL) or by a bedside blind insertion technique (BI) under local anaesthesia.

AKI in early sepsis is a continuum from transient AKI without tubular damage over transient AKI with minor tubular damage to intrinsic AKI with severe tubular damage.

PURPOSE: The pathophysiology of septic acute kidney injury (AKI) is incompletely understood, and there is controversy on the role of renal hypoperfusion in early sepsis. We hypothesized that renal hypoperfusion plays a role in early sepsis and that there is a continuum between transient AKI without tubular damage, transient AKI with minor tubular damage, and intrinsic AKI. METHODS: A total of 107 consecutive patients with sepsis were included. Fractional excretion of sodium (FENa), urinary, and serum neutrophil gelatinase-associated lipocalin were measured at admission (T0) and 4 h (T4) and 24 h later (T24). Patients were classified according to FENa quartiles (FENaQ). Transient and intrinsic AKI were respectively defined as AKI that did or did not recover to no AKI in the following 5 days. RESULTS: A total of 57 developed transient AKI, 22 developed intrinsic AKI, and 28 did not have AKI. Of the ten patients with transient AKI classified in the two lowest FENa quartiles (FENa < 0.36 %) and without signs of local tubular damage, seven still did not show signs of tubular damage 24 h later. Also, 50 % of patients with intrinsic AKI classified in the same FENaQ did not show signs of local tubular damage at admission but did so 24 h later. CONCLUSIONS: There is a continuum between transient AKI without tubular damage, transient AKI with minor tubular damage, and intrinsic AKI in sepsis. Renal hypoperfusion seems to be the instigator for the development of AKI in the majority of patients with early sepsis. Other mechanisms in some patients cannot be excluded.

Blood pressure management in patients with chronic kidney disease: an appraisal and summary of existing guidelines.

BACKGROUND: Hypertension is a prevalent problem with huge impact on health and health care budgets. Several guidelines on how to manage blood pressure have been published, and it is unclear which one should be preferred. METHODS: Eight guidelines dealing with blood pressure management of chronic kidney disease patients were evaluated for methodological quality by the AGREE II instrument by 4 appraisers. They were also analysed for consistency in their recommendations. RESULTS: Most problematic domains were "applicability", "stakeholder involvement" and "editorial independence". Three guidelines scored below 50% for 5, and one for 4 of the 6 AGREE II domains. The guideline produced by Canadian Hypertension Education Program was preferred most, followed by KDIGO. There were discrepancies between the different guidelines with regard to blood pressure targets and thresholds, with the best and most recent advocating 140/90 mmHg. There was a consensus on the use of ACE-I/ARB's in patients with but not for those without proteinuria. However, only two guidelines specify a second line treatment (thiazides), whereas others do not, although it is well known that most patients need more than one drug to control their blood pressure. Three out of eight guidelines did not provide guidance on life-style modification. Those who did, advocated different levels of sodium restriction,, weight control, and physical activity. Remarkably, 5 out of 8 guidelines did not specify how exactly blood pressure should be measured. CONCLUSION: Blood pressure guidelines seem to be of low methodological quality, with clear improvements for the ones produced the latest. Especially the "applicability" domain, evaluating how the guideline can be put into practice, seems problematic, with as biggest hurdles that it is unclear what should be second or third line treatments, and how blood pressure should be measured or defined. The most recent guidelines advocate an office blood pressure of 140/90 mmHg for patients with chronic kidney disease.