Wars, disasters and kidneys.

This paper summarizes the impact that wars had on the history of nephrology, both worldwide and in the Ghent Medical Faculty notably on the definition, research and clinical aspects of acute kidney injury. The paper briefly describes the role of 'trench nephritis' as observed both during World War I and II, supporting the hypothesis that many of the clinical cases could have been due to Hantavirus nephropathy. The lessons learned from the experience with crush syndrome first observed in World War II and subsequently investigated over many decades form the basis for the creation of the Renal Disaster Relief Task Force of the International Society of Nephrology. Over the last 15 years, this Task Force has successfully intervened both in the prevention and management of crush syndrome in numerous disaster situations like major earthquakes.

What is the difference between prerenal and renal acute kidney injury?

This paper discusses the somewhat artificial distinction between the traditional classification of acute kidney injury in prerenal AKI and established acute tubular necrosis. The primary focus in the setting of a rising SCr should not be assigning the diagnosis of"prerenal" or "renal" AKI but should be determining where the dysfunction lies on the spectrum between purely "functional"and completely structural kidney damage. The new definitions and classification systems of AKI are summarised and the approach to the patient with acute rising serum creatinine and/or acute decline in urinary output is described. The role of the recently introduced novel biomarkers is discussed but it is believed that these biomarkers have not yet proven to be more discriminative in the differential diagnosis between"pure prerenal AKI"and established acute tubular necrosis, beyond a careful clinical evaluation of the patient and the use of the more "traditional" blood and urine parameters.

Nephrotoxicity of anticancer drugs--an underestimated problem?

Nephrotoxicity is an inherent adverse effect of certain anticancer drugs and may result in a variety of functional consequences that include any combination of glomerular or tubular dysfunction, hypertension and disturbance of the renal endocrine function. The nephrotoxic potential of most anticancer agents dramatically increases in the presence of borderline or overt pre-existing chronic kidney disease and measurement of renal function is therefore of utmost importance in the cancer patient before any treatment is initiated. This review summarizes some clinical nephrotoxic side effects of a selection of the most frequently used anticancer drugs. The drugs discussed are cisplatin, methotrexate, ifosfamide, citumixab and panitumumab, mitocin C and gemcitabine and antiangiogenesis drugs.

Characteristics, cardiovascular comorbidity and medicines management in patients with type 2 diabetes and CKD: results of the IRIDIEM study.

BACKGROUND: Type 2 diabetes is a leading cause of chronic kidney disease (CKD). The purpose of the Individual Risk-Profiling and Treatment in Diabetes Management (IRIDIEM) study was to evaluate the characteristics of CKD and associated comorbidities in patients with type 2 diabetes and CKD. METHODS: IRIDIEM was conducted as a cross-sectional survey in 109 centres in 11 countries and included 1,205 patients aged >or=50 years with type 2 diabetes for >or=5 years and CKD stage 2-4. RESULTS: 50% of patients were in CKD stage 4; 42% had CKD stage 3, and 4% were in CKD stage 2. Concomitant risk factors for cardiovascular disease and/or progression of CKD included hypertension (92% of patients), proteinuria (74%), hypercholesterolaemia (65%), and hypertriglyceridaemia (44%). Only 64% of patients with hypertension had received antihypertensive medication. Anaemia was present in 34% of patients and increased markedly with advanced CKD stages. Of patients with documented anaemia, only 19% had received epoetin and only 7% had received iron treatment. CONCLUSION: IRIDIEM documents the need to improve adherence to current best practice guidelines for management of cardiorenal risk factors including earlier initiation of antihypertensive treatment, lipid and anaemia management in this high-risk patient population.

Costs and length of stay associated with antimicrobial resistance in acute kidney injury patients with bloodstream infection.

INTRODUCTION: Antimicrobial resistance negatively impacts on prognosis. Intensive care unit (ICU) patients, and particularly those with acute kidney injury (AKI), are at high risk for developing nosocomial bloodstream infections (BSI) due to multi-drug-resistant strains. Economic implications in terms of costs and length of stay (LOS) attributable to antimicrobial resistance are underevaluated. This study aimed to assess whether microbial susceptibility patterns affect costs and LOS in a well-defined cohort of ICU patients with AKI undergoing renal replacement therapy (RRT) who developed nosocomial BSI. METHODS: Historical study (1995-2004) enrolling all adult RRT-dependent ICU patients with AKI and nosocomial BSI. Costs were considered as invoiced in the Belgian reimbursement system, and LOS was used as a surrogate marker for hospital resource allocation. RESULTS: Of the 1330 patients with AKI undergoing RRT, 92 had microbiologic evidence of nosocomial BSI (57/92, 62% due to a multi-drug-resistant microorganism). Main patient characteristics were equal in both groups. As compared to patients with antimicro-4 bial-susceptible BSI, patients with antimicrobial-resistant BSI were more likely to acquire Gram-positive infection (72.6% vs 25.5%, P<0.001). No differences were found neither in LOS (ICU before BSI, ICU, hospital before BSI, hospital, hospital after BSI, and time on RRT; all P>0.05) or hospital costs (all P>0.05) when comparing patients with antimicrobial-resistant vs antimicrobial-susceptible BSI. However, although not statistically significant, patients with BSI caused by resistant Gram-negative-, Candida-, or anaerobic bacteria incurred substantial higher costs than those without. CONCLUSION: In a cohort of ICU patients with AKI and nosocomial BSI undergoing RRT, patients with antimicrobial-resistant vs antimicrobial-susceptible Gram-positive BSI did not have longer hospital stays, or higher hospital costs. Patients with resistant "other" (i.e. Gram-negative, Candida, or anaerobic) BSI were found to have a distinct trend towards increased resources use as compared to patients with susceptible "other" BSI, respectively.

Chronic kidney disease as a global public health problem: approaches and initiatives - a position statement from Kidney Disease Improving Global Outcomes.

Chronic kidney disease (CKD) is increasingly recognized as a global public health problem. There is now convincing evidence that CKD can be detected using simple laboratory tests, and that treatment can prevent or delay complications of decreased kidney function, slow the progression of kidney disease, and reduce the risk of cardiovascular disease (CVD). Translating these advances to simple and applicable public health measures must be adopted as a goal worldwide. Understanding the relationship between CKD and other chronic diseases is important to developing a public health policy to improve outcomes. The 2004 Kidney Disease Improving Global Outcomes (KDIGO) Controversies Conference on 'Definition and Classification of Chronic Kidney Disease' represented an important endorsement of the Kidney Disease Outcome Quality Initiative definition and classification of CKD by the international community. The 2006 KDIGO Controversies Conference on CKD was convened to consider six major topics: (1) CKD classification, (2) CKD screening and surveillance, (3) public policy for CKD, (4) CVD and CVD risk factors as risk factors for development and progression of CKD, (5) association of CKD with chronic infections, and (6) association of CKD with cancer. This report contains the recommendations from the meeting. It has been reviewed by the conference participants and approved as position statement by the KDIGO Board of Directors. KDIGO will work in collaboration with international and national public health organizations to facilitate implementation of these recommendations.

Dopps estimate of patient life years attributable to modifiable haemodialysis practices in Belgium.

BACKGROUND: Various organizations have published clinical practice guidelines for the care of haemodialysis patients. However, it is unknown to what extent improving or even reaching perfect compliance with guidelines would improve the survival of HD patients in Belgium. METHODS: Using data from the second phase of the Dialysis Outcomes and Practice Patterns Study (DOPPS), the proportion of haemodialysis patients failing to meet six key practice targets (Kt/V > or = 1.2, haemoglobin > or =11 g/dl, phosphate 1.1-1.5 mmol/l, calcium 2.1-2, 4 mmol/l, albumin > or =40 g/l, and facility catheter use < or =10%) was calculated along with the relative risk of mortality associated with being outside these targets. The life years potentially gained from adherence to the six targets, both separately and all six together were then estimated. RESULTS: The percentage of patients outside the targets were as follows: 30.3%, Kt/V; 33.6%, haemoglobin; 56.2%, phosphate; 58.2%, calcium; 67.1%, albumin; and 91.1%, catheter. Estimated patient life years gained with improved compliance with guidelines was highest for albumin (3.670) and catheter use (2.331) but still substantial for the other four targets (ranging from 551 to 1.258). The total of patient years gained if 100% of patients have all six practices brought within target reaches 7.516 years. A conservative estimate of 50% of patients within all targets still yields an improvement of survival of 3.958 patient years. CONCLUSION: This analysis suggests large opportunities to improve HD patient care in Belgium. The avoidance of HD catheters, with the use of AV fistulas whenever possible, should be given a high priority. Admittedly, these calculations assume causality or partial causality that has not been definitively proven. Still, if causality is only partial, the results emphasize that the improvement of patient care through adherence to targets of clinical guidelines might be substantial and all Belgian nephrologists and staff members of dialysis units should carefully pursue every potential effort.

The role of the International Society of Nephrology/Renal Disaster Relief Task Force in the rescue of renal disaster victims.

Disasters are a major cause of distress and material as well as corporal damage. Next to direct trauma, the crush syndrome inducing multiorgan problems as a consequence of muscle compression and the release of muscular contents into the bloodstream is the most important cause of death; this is to a large extent related to the induction of severe acute kidney injury, for which dialysis is a life-saving therapy. The practical means (both hardware and personnel) to do so are, however, often lacking in disaster conditions. The Renal Disaster Relief Task Force (RDRTF) offered support for renal problems in the aftermath of several disasters, e.g. the Marmara earthquake (1999) in Turkey, the Bam earthquake (2003) in Iran, and the Kashmir earthquake (2005) in Pakistan. A preconceived intervention plan is followed with adaptations according to local conditions. Material and personnel are dispatched to the disaster areas. These interventions have been life-saving for a substantial number of victims. The current article describes the structure and approach of the RDRTF.

The Kidney Disease: improving Global Outcomes website: comparison of guidelines as a tool for harmonization.

Chronic kidney disease (CKD) is a worldwide public health problem with significant comorbidity and mortality. Improving quality of life and survival of CKD patients necessitates a large number of preventive and therapeutic interventions. To resolve these issues several organizations have developed guidelines, which are difficult to compare comprehensively. The Kidney Disease: Improving Global Outcomes website at http://kdigo.org compares five major guidelines. The section 'compare guidelines' covers 41 topics distributed over five major subjects: (1) general clinics; (2) hemodialysis (HD); (3) vascular access for HD; (4) peritoneal dialysis; and (5) chemistries. The tables compare guideline recommendations and the evidence levels on which they are based, with direct links to each of the guidelines. These data show that the different guideline groups tend to propose similar targets, but that nuances in the guideline statements, their rationale, and grading of evidence levels present some discrepancies, although most guidelines are based on the same literature. We conclude that there is an urgent need to harmonize existing guidelines, and for a global initiative to avoid the parallel development of conflicting guidelines on the same topics. The tables displayed on the website offer a basis for structuring this process, a procedure which has recently been initiated by a body composed of the five guideline development groups.

Grading evidence and recommendations for clinical practice guidelines in nephrology. A position statement from Kidney Disease: Improving Global Outcomes (KDIGO).

Considerable variation in grading systems used to rate the strength of guideline recommendations and the quality of the supporting evidence in Nephrology highlights the need for a uniform, internationally accepted, rigorous system. In 2004, Kidney Disease: Improving Global Outcomes (KDIGO) commissioned a methods expert group to recommend an approach for grading in future nephrology guidelines. This position statement by KDIGO recommends adopting the Grades of Recommendation Assessment, Development, and Evaluation (GRADE) approach for the grading of evidence and guidelines on interventions. The GRADE approach appraises systematic reviews of the benefits and harms of an intervention to determine its net health benefit. The system considers the design, quality, and quantity of studies as well as the consistency and directness of findings when grading the quality of evidence. The strength of the recommendation builds on the quality of the evidence and additional considerations including costs. Adaptations of the GRADE approach are presented to address some issues pertinent to the field of nephrology, including (1) the need to extrapolate from studies performed predominantly in patients without kidney disease, and (2) the need to use qualitative summaries of effects when it is not feasible to quantitatively summarize them. Further refinement of the system will be required for grading of evidence on questions other than those related to intervention effects, such as diagnostic accuracy and prognosis.

Evaluation of the peritoneal membrane function by three letter word acronyms: PET, PDC, SPA, PD-Adequest, POL: what to do?

This paper describes and reviews different methods to evaluate the peritoneal transport capacity. This evaluation is important because it will influence the preferred treatment regimen, and will also be a tool for longitudinal follow up both in the individual patient as in patient groups.

Effects of peritoneal dialysis on the vascular bed of peritoneal membrane.

The vascularization of the peritoneal membrane is a key factor in the effectiveness of peritoneal dialysis as a dialysis modality. Over the last years, our understanding of how the peritoneal vasculature reacts to instillation of peritoneal dialysate has substantially improved. The changes in the structure of the peritoneal function over time on peritoneal dialysis as found in functional tests has been confirmed in biopsy studies performed on patients. These show both neoangiogenesis and fibrosis as the underlying morphological changes contributing to these phenomena. A thorough understanding of the biological processes involved in these alterations will be the clue for improvement of the treatment and a key to develop strategies to avoid these deformations.

The impact of the pre-transplant renal replacement modality on outcome after cadaveric kidney transplantation: the ghent experience.

For suitable patients, renal transplantation is still the most preferable renal replacement modality, offering the best outcome in terms of survival and quality of life [Meier-Kriesche, H.U. et al: Semin Dial 2005;18:499-504]. The shorter the period on dialysis, the better the outcome after transplantation seems to be [Meier-Kriesche, H.U. et al: Transplantation 2002;74: 1377-1381]. However, for most patients, a pre-emptive transplantation is not an option by lack of a suitable organ. Therefore, most people have to undergo hemodialysis or peritoneal dialysis (PD) while awaiting a donor kidney. There is evidence that PD positively impacts on the outcome after transplantation [Van Loo, A.A. et al: J Am Soc Nephrol 1998;9:473-481], an effect that could be attributed to a more stable fluid homeostasis, but also to an independent effect of biocompatibility of the dialysis membrane [Van Biesen, W. et al: Transplantation 2000;69:508-514], which is by definition better in PD. Based on these findings, since 1999, all hemodialysis patients at the university of Ghent are dialyzed on a low complement activating dialyzer, and dialysis and especially ultrafiltration in the 24 h preceding the transplantation are avoided as much as possible. A recent re-analysis of the data of the outcome of our transplant program showed that this approach resulted in a reduction of delayed graft function in the hemodialysis patients, allowing to reach an outcome level comparable to that of the PD patients. However, the long-term patient survival still is slightly superior in the PD patients.

Definition, evaluation, and classification of renal osteodystrophy: a position statement from Kidney Disease: Improving Global Outcomes (KDIGO).

Disturbances in mineral and bone metabolism are prevalent in chronic kidney disease (CKD) and are an important cause of morbidity, decreased quality of life, and extraskeletal calcification that have been associated with increased cardiovascular mortality. These disturbances have traditionally been termed renal osteodystrophy and classified based on bone biopsy. Kidney Disease: Improving Global Outcomes (KDIGO) sponsored a Controversies Conference on Renal Osteodystrophy to (1) develop a clear, clinically relevant, and internationally acceptable definition and classification system, (2) develop a consensus for bone biopsy evaluation and classification, and (3) evaluate laboratory and imaging markers for the clinical assessment of patients with CKD. It is recommended that (1) the term renal osteodystrophy be used exclusively to define alterations in bone morphology associated with CKD, which can be further assessed by histomorphometry, and the results reported based on a unified classification system that includes parameters of turnover, mineralization, and volume, and (2) the term CKD-Mineral and Bone Disorder (CKD-MBD) be used to describe a broader clinical syndrome that develops as a systemic disorder of mineral and bone metabolism due to CKD, which is manifested by abnormalities in bone and mineral metabolism and/or extra-skeletal calcification. The international adoption of these recommendations will greatly enhance communication, facilitate clinical decision-making, and promote the evolution of evidence-based clinical practice guidelines worldwide.