Review

Authors: S Vincent Rajkumar, Meletios A Dimopoulos, Antonio Palumbo...

This International Myeloma Working Group consensus updates the disease definition of multiple myeloma to include validated biomarkers in addition to existing requirements of attributable CRAB features (hypercalcaemia, renal failure, anaemia, and bone lesions). These changes are based on the identification of biomarkers associated with near inevitable development of CRAB features in patients who would otherwise be regarded as having smouldering multiple myeloma. A delay in application of the label of multiple myeloma and postponement of therapy could be detrimental to these patients. In addition to this change, we clarify and update the underlying laboratory and radiographic variables that fulfil the criteria for the presence of myeloma-defining CRAB features, and the histological and monoclonal protein requirements for the disease diagnosis. Finally, we provide specific metrics that new biomarkers should meet for inclusion in the disease definition. The International Myeloma Working Group recommends the implementation of these criteria in routine practice and in future clinical trials, and recommends that future studies analyse any differences in outcome that might occur as a result of the new disease definition.

Topics: Biomarkers, Tumor; Bone Marrow Cells; Humans; Multiple Myeloma; Prognosis; Renal Insufficiency

PubMed: 25439696
DOI: 10.1016/S1470-2045(14)70442-5

Review

Authors: Adriano Luiz Ammirati

Chronic kidney disease is highly prevalent (10-13% of the population), irreversible, progressive, and associated with higher cardiovascular risk. Patients with this pathology remain asymptomatic most of the time, presenting the complications typical of renal dysfunction only in more advanced stages. Its treatment can be conservative (patients without indication for dialysis, usually those with glomerular filtration rate above 15 ml/minute) or replacement therapy (hemodialysis, peritoneal dialysis, and kidney transplantation). The objectives of the conservative treatment for chronic kidney disease are to slow down the progression of kidney dysfunction, treat complications (anemia, bone diseases, cardiovascular diseases), vaccination for hepatitis B, and preparation for kidney replacement therapy.

Topics: Humans; Kidney Failure, Chronic; Prevalence; Renal Dialysis; Renal Insufficiency; Renal Insufficiency, Chronic; Risk Factors

PubMed: 31939529
DOI: 10.1590/1806-9282.66.S1.3

Authors: Paul E Stevens, Adeera Levin, ...

DESCRIPTION

The Kidney Disease: Improving Global Outcomes (KDIGO) organization developed clinical practice guidelines in 2012 to provide guidance on the evaluation, management, and treatment of chronic kidney disease (CKD) in adults and children who are not receiving renal replacement therapy.

METHODS

The KDIGO CKD Guideline Development Work Group defined the scope of the guideline, gathered evidence, determined topics for systematic review, and graded the quality of evidence that had been summarized by an evidence review team. Searches of the English-language literature were conducted through November 2012. Final modification of the guidelines was informed by the KDIGO Board of Directors and a public review process involving registered stakeholders.

RECOMMENDATIONS

The full guideline included 110 recommendations. This synopsis focuses on 10 key recommendations pertinent to definition, classification, monitoring, and management of CKD in adults.

Topics: Acute Kidney Injury; Adult; Albuminuria; Child; Disease Progression; Glomerular Filtration Rate; Humans; Monitoring, Physiologic; Practice Guidelines as Topic; Renal Insufficiency, Chronic

PubMed: 23732715
DOI: 10.7326/0003-4819-158-11-201306040-00007

Review

Authors: Claudio Ronco, Mikko Haapio, Andrew A House...

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

Topics: Acute Disease; Chronic Disease; Disease Progression; Female; Heart Failure; Heart Function Tests; Humans; Kidney Function Tests; Male; Prognosis; Renal Insufficiency; Severity of Illness Index; Syndrome; Terminology as Topic

PubMed: 19007588
DOI: 10.1016/j.jacc.2008.07.051

Authors: Lakhmir S Chawla, Rinaldo Bellomo, Azra Bihorac...

Consensus definitions have been reached for both acute kidney injury (AKI) and chronic kidney disease (CKD) and these definitions are now routinely used in research and clinical practice. The KDIGO guideline defines AKI as an abrupt decrease in kidney function occurring over 7 days or less, whereas CKD is defined by the persistence of kidney disease for a period of >90 days. AKI and CKD are increasingly recognized as related entities and in some instances probably represent a continuum of the disease process. For patients in whom pathophysiologic processes are ongoing, the term acute kidney disease (AKD) has been proposed to define the course of disease after AKI; however, definitions of AKD and strategies for the management of patients with AKD are not currently available. In this consensus statement, the Acute Disease Quality Initiative (ADQI) proposes definitions, staging criteria for AKD, and strategies for the management of affected patients. We also make recommendations for areas of future research, which aim to improve understanding of the underlying processes and improve outcomes for patients with AKD.

Topics: Acute Kidney Injury; Humans; Remission Induction; Renal Insufficiency, Chronic

PubMed: 28239173
DOI: 10.1038/nrneph.2017.2

Review

Authors: Chengyuan Tang, Juan Cai, Xiao-Ming Yin...

Mitochondria are essential for the activity, function and viability of eukaryotic cells and mitochondrial dysfunction is involved in the pathogenesis of acute kidney injury (AKI) and chronic kidney disease, as well as in abnormal kidney repair after AKI. Multiple quality control mechanisms, including antioxidant defence, protein quality control, mitochondrial DNA repair, mitochondrial dynamics, mitophagy and mitochondrial biogenesis, have evolved to preserve mitochondrial homeostasis under physiological and pathological conditions. Loss of these mechanisms may induce mitochondrial damage and dysfunction, leading to cell death, tissue injury and, potentially, organ failure. Accumulating evidence suggests a role of disturbances in mitochondrial quality control in the pathogenesis of AKI, incomplete or maladaptive kidney repair and chronic kidney disease. Moreover, specific interventions that target mitochondrial quality control mechanisms to preserve and restore mitochondrial function have emerged as promising therapeutic strategies to prevent and treat kidney injury and accelerate kidney repair. However, clinical translation of these findings is challenging owing to potential adverse effects, unclear mechanisms of action and a lack of knowledge of the specific roles and regulation of mitochondrial quality control mechanisms in kidney resident and circulating cell types during injury and repair of the kidney.

Topics: Acute Kidney Injury; Animals; Humans; Mitochondria; Renal Insufficiency, Chronic

PubMed: 33235391
DOI: 10.1038/s41581-020-00369-0

Review

Authors: Monica Chang-Panesso

Our aging population is growing and developing treatments for age-related diseases such as Alzheimer's and Parkinson's disease has taken on an increasing urgency and is accompanied by high public awareness. The already high and rising incidence of acute kidney injury (AKI) in the elderly, however, has received relatively little attention despite the potentially fatal outcomes associated with an episode of AKI in this age group. When discussing AKI and aging, one should consider two aspects: first, elderly patients have an increased susceptibility to an AKI episode, and second, they have decreased kidney repair after AKI given the high incidence of progression to chronic kidney disease (CKD). It is unclear if the same factors that drive the increased susceptibility to AKI could be playing a role in the decreased repair capacity or if they are totally different and unrelated. This review will examine current knowledge on the risk factors for the increased susceptibility to AKI in the elderly and will also explore potential aspects that might contribute to a decreased kidney repair response in this age group.

Topics: Acute Kidney Injury; Aged; Aging; Disease Progression; Humans; Kidney; Renal Insufficiency, Chronic; Risk Factors

PubMed: 33411069
DOI: 10.1007/s00467-020-04849-0

Review

Authors: Aleksandar Denic, Richard J Glassock, Andrew D Rule...

Senescence or normal physiologic aging portrays the expected age-related changes in the kidney as compared to a disease that occurs in some but not all individuals. The microanatomical structural changes of the kidney with older age include a decreased number of functional glomeruli from an increased prevalence of nephrosclerosis (arteriosclerosis, glomerulosclerosis, and tubular atrophy with interstitial fibrosis), and to some extent, compensatory hypertrophy of remaining nephrons. Among the macroanatomical structural changes, older age associates with smaller cortical volume, larger medullary volume until middle age, and larger and more numerous kidney cysts. Among carefully screened healthy kidney donors, glomerular filtration rate (GFR) declines at a rate of 6.3 mL/min/1.73 m(2) per decade. There is reason to be concerned that the elderly are being misdiagnosed with CKD. Besides this expected kidney function decline, the lowest risk of mortality is at a GFR of ≥75 mL/min/1.73 m(2) for age <55 years but at a lower GFR of 45 to 104 mL/min/1.73 m(2) for age ≥65 years. Changes with normal aging are still of clinical significance. The elderly have less kidney functional reserve when they do actually develop CKD, and they are at higher risk for acute kidney injury.

Topics: Aged; Aged, 80 and over; Aging; Glomerular Filtration Rate; Humans; Kidney; Renal Insufficiency

PubMed: 26709059
DOI: 10.1053/j.ackd.2015.08.004

Review

Authors: Yin-Wu Bao, Yuan Yuan, Jiang-Hua Chen...

Acute kidney injury (AKI) and chronic kidney disease (CKD) are worldwide public health problems affecting millions of people and have rapidly increased in prevalence in recent years. Due to the multiple causes of renal failure, many animal models have been developed to advance our understanding of human nephropathy. Among these experimental models, rodents have been extensively used to enable mechanistic understanding of kidney disease induction and progression, as well as to identify potential targets for therapy. In this review, we discuss AKI models induced by surgical operation and drugs or toxins, as well as a variety of CKD models (mainly genetically modified mouse models). Results from recent and ongoing clinical trials and conceptual advances derived from animal models are also explored.

Topics: Acute Kidney Injury; Animals; Disease Models, Animal; Humans; Kidney Diseases; Mice; Rats; Renal Insufficiency, Chronic

PubMed: 29515089
DOI: 10.24272/j.issn.2095-8137.2017.055

Review

Authors: Amanda DeMauro Renaghan, Edgar A Jaimes, Jolanta Malyszko...

Hematopoietic stem cell transplantation is a life-saving therapy for many patients with cancer, as well as patients with some nonmalignant hematologic disorders, such as aplastic anemia, sickle cell disease, and certain congenital immune deficiencies. Kidney injury directly associated with stem cell transplantation includes a wide range of structural and functional abnormalities, which may be vascular (hypertension, thrombotic microangiopathy), glomerular (albuminuria, nephrotic glomerulopathies), and/or tubulointerstitial. AKI occurs commonly after stem cell transplant, affecting 10%-73% of patients. The cause is often multifactorial and can include sepsis, nephrotoxic medications, marrow infusion syndrome, hepatic sinusoidal obstruction syndrome, thrombotic microangiopathy, infections, and graft versus host disease. The risk of post-transplant kidney injury varies depending on patient characteristics, type of transplant (allogeneic versus autologous), and choice of chemotherapeutic conditioning regimen (myeloablative versus nonmyeloablative). Importantly, AKI is associated with substantial morbidity, including the need for KRT in approximately 5% of patients and the development of CKD in up to 60% of transplant recipients. AKI has been associated universally with higher all-cause and nonrelapse mortality regardless of transplant type, and studies have consistently shown extremely high (>80%) mortality rates in those patients requiring acute dialysis. Accordingly, prevention, early recognition, and prompt treatment of kidney injury are essential to improving kidney and patient outcomes after hematopoietic stem cell transplantation, and for realizing the full potential of this therapy.

Topics: Acute Kidney Injury; Early Diagnosis; Hematopoietic Stem Cell Transplantation; Humans; Incidence; Renal Insufficiency, Chronic; Risk Assessment; Risk Factors; Treatment Outcome

PubMed: 31836598
DOI: 10.2215/CJN.08580719