- Weekly Curriculum Resources
Disorders of Water and Sodium Balance
By Richard H Sterns, MD, FACPPurchase PDF
Disorders of Water and Sodium BalancePurchase PDF
Water accounts for approximately half of an adult human’s body weight. Two thirds of body water is intracellular, and the remaining one third is contained in the extracellular fluid compartment, which includes intravascular (plasma) and interstitial fluid. Small amounts of water are also contained in bone, dense connective tissue, digestive secretions, and cerebrospinal fluid. To maintain the stability of the internal milieu, body fluids are processed by the kidney, guided by intricate physiologic control systems that regulate fluid volume and composition. This chapter reviews the regulation of body fluid volumes, cell volume regulation in hypotonicity and hypertonicity, disorders of water excess (hyponatremia), water deficiency (hypernatremia), water conservation (diabetes insipidus), saltwater excess (edematous states), and saltwater deficiency (volume depletion). Tables describe control of body fluid volumes, causes of nonhypotonic hyponatremia, causes and treatment of acute hyponatremia, causes of the syndrome of inappropriate release of antidiuretic hormone (SIADH), and causes of hypernatremia. Figures illustrate sodium reabsorption by the renal tubules, the relationship between plasma vasopressin levels, renal sodium handling, and dose-response curves for a loop diuretic in patients with normal and reduced renal function.
This chapter contains 4 highly rendered figures, 5 tables, 88 references, and 5 MCQs.
Pharmacologic Approach to Renal Insufficiency
By Ali J. Olyaei, PharmD; William M. Bennett, MDPurchase PDF
Pharmacologic Approach to Renal InsufficiencyPurchase PDF
Prescribing drugs in patients with kidney disease is complex: drug dosing needs to be adjusted by the stage of kidney disease (whether chronic kidney disease [CKD] stages 1 through 5 or acute kidney injury [AKI] stages 1 through 3); because potential interactions with other agents that are being used need to be considered; and because of the possibility of extracorporeal treatment that might need to be used (e.g., continuous renal replacement therapy [CRRT], peritoneal dialysis [PD], or hemodialysis [HD]). Besides this complexity, there has been an explosion in the classes of new agents and the routes of delivery of these agents. The purpose of this chapter is to review the basic pharmacokinetic and pharmacologic principles that should guide therapy and to summarize basic recommendations for patients with CKD and AKI. The general principles for drug dosing in CKD and AKI include pharmacokinetics in renal failure; bioavailability; volume of distribution; protein binding; and biotransformation. A stepwise approach to dosage adjustment is described and created as an algorithmic approach. Drug dosing considerations in dialysis patients and in AKI patients are covered as well.
This chapter contains 2 algorithms, 7 tables, 25 references, 5 Board-styled MCQs, and 1 Teaching Slide Set.
Benign Prostatic Hyperplasia
By Michael J Barry, MD, FACPPurchase PDF
Benign Prostatic HyperplasiaPurchase PDF
Benign prostatic hyperplasia (BPH) is a common cause of morbidity in older men in developed countries. BPH causes lower urinary tract symptoms (LUTS) and occasionally results in such complications as acute urinary retention (AUR), urinary tract infection, and even obstructive uropathy. Although the development of medical treatments has reduced the role of surgery, prostatectomy remains a widely performed procedure. Epidemiology, risk factors, and pathophysiology are discussed. Diagnosis includes clinical features, history, physical examination, and laboratory testing. Management can include watchful waiting, medical treatment, surgery, and minimally invasive treatment. Management of AUR is also addressed. A table lists the alpha blockers commonly used in the treatment of men with LUTS attributed to BPH. Figures illustrate the prevalence of BPH histology with age, the anatomy of the prostate gland, the International Prostate Symptom Score (IPSS) for assessing BPH, and 4-year outcomes in men with moderate and severe LUTS attributable to BPH.
This chapter contains 4 highly rendered figures, 1 table, 70 references, and 5 MCQs.
Kidney Transplantation 1: an Overview--recipient Evaluation and Immunosuppression
By Jamil Azzi, MD; Belinda T. Lee, MD; Anil Chandraker, MDPurchase PDF
Kidney Transplantation 1: an Overview--recipient Evaluation and ImmunosuppressionPurchase PDF
Half a century after the first successful kidney transplantation, we still stand at the crossroads of immunology and transplantation, where science meets art in the management of complex end-stage renal disease (ESRD) patients. Successful transplantation requires not only a lifetime’s commitment from patients but also a multidisciplinary approach, bringing together surgeons, transplant nephrologists, primary care physicians, scientists, and nurses to provide coordinated care. Although transplantation is the treatment of choice for the vast majority of ESRD patients, many patients remain on dialysis due to a relative imbalance between demand for and supply of suitable organs. This chapter provides a comprehensive overview of recipient evaluation and immunosuppression. Risk factors that prohibit transplantation are discussed, as are human leukocyte antigen/ABO compatibility, transplant immunobiology, induction therapy, maintenance therapy, transplantation for special populations, and future directions in the field. Tables outline Amsterdam Living Donation Forum guidelines, ABO blood group compatibilities, and pretransplant immunologic testing. Visual aids include graphs, charts, cell illustrations, and an evaluative algorithm.
This chapter contains 10 figures, 3 tables, 101 references, and 5 Board-styled MCQs.
Kidney Transplantation 2: Care of the Kidney Transplant Recipient
By Jamil Azzi, MD; Belinda T. Lee, MD; Anil Chandraker, MDPurchase PDF
Kidney Transplantation 2: Care of the Kidney Transplant RecipientPurchase PDF
This chapter discusses the goals and challenges of caring for the kidney transplant recipient. This area has become increasingly specialized in recent years, with physicians needing a good understanding of immunology, nephrology, pharmacology, and infectious diseases as well as a good grasp of internal medicine. Topics covered include cardiovascular disease, new on-set diabetes, hypertension, dyslipidemia, infectious complications, malignancy, bone disease, recurrence of disease, drug reactions, rejection, and other challenges that face the kidney transplant population. Tables outline relevant medications, recommended vaccines, virus-associated malignancies, cancer rates, common drug interactions, and diagnostic categories. Figures include graphs, charts, and microscopic photos.
This chapter contains 7 figures, 7 tables, 111 references, and 5 Board-styled MCQs.
Kidney Disease in the Cancer Patient
By Colm Magee, MD, MPH, FRCPI; Lynn Redahan, MD, MRCPIPurchase PDF
Kidney Disease in the Cancer PatientPurchase PDF
The spectrum of kidney disease in the cancer patient is wide. Kidney dysfunction can result from the cancer itself or its treatment. The presentation in this population is varied and may manifest as acute kidney injury (AKI) or chronic kidney disease. In addition, other manifestations of kidney disease can include proteinuria, hypertension, and electrolyte disturbances. As new cancer treatments emerge, the range of therapy-associated renal syndromes increases. This chapter deals predominantly with causes and management of renal dysfunction that are specific to the cancer patient, including those caused by hypercalcemia; hepatorenal syndrome; the use of interleukin-2 (IL-2) and bisphosphonate; glomerular, tubular, interstitial, and vascular diseases; multiple myeloma (MM); and tumor infiltration. The chapter also examines postrenal causes of AKI, electrolyte disorders, and hematopoietic stem cell transplantation (HSCT). Tables provide the features of kidney disease in the cancer patient, the pathogenesis of hypercalcemia, strategies for preventing and managing AKI with IL-2 therapy, laboratory findings with hemolytic-uremic syndrome/thrombocytopenic purpura, the causes of acute tubular necrosis in MM, a summary of electrolyte disturbances in the cancer patient, indications for HSCT, and a summary of the management of patients with post-HSCT AKI. The chapter is also enhanced by ultrasound and computed tomographic scans, histology images, and an illustration of tumor lysis syndrome.
This chapter contains 105 references, 8 tables, 4 highly rendered figures, and 5 MCQs.
- Lab Assessment
By Gautam Kishore Valecha , MBBS; Rafeel Syed, MD; Amina Rehman, MBBS; Suzanne El-Sayegh, MDPurchase PDF
Urinalysis comprises physical, chemical, and microscopic examination of urine. Although widely available, this test is often underused and misinterpreted. Urinalysis can provide helpful clues in the assessment of a variety of clinical conditions, but one must be aware of their limitations. On proper collection, the sample must be analyzed ideally within 2 hours. Dipstick urinalysis is convenient and commonly performed but provides qualitative or semiquantitative assessment only, and its results can be affected by urine discoloration and the presence of various other substances. Finally, urine microscopy is an important component of urinalysis used to identify various structures such as crystals, cells, microorganisms, and casts, which in turn helps in the assessment of the underlying disease. In this review, we discuss the clinical implications of various findings on urinalysis. Additionally, we also highlight the importance of proper sample collection and examination techniques to optimize the diagnostic yield of this invaluable test.
- Renal Transplantation
By Ilaria Gandolfini, MD; Paolo Cravedi, MD, PhDPurchase PDF
Transplantation ImmunobiologyPurchase PDF
The immune system has evolved to clear the host of invading microorganisms and its own cells that have become altered in some way, such as infected cells or mutated tumorigenic cells. The immune system recognizes such cells as “foreign” based on their expression of different molecules (antigens). Similarly, when organs are transplanted between genetically disparate (allogeneic) individuals, the immune system recognizes and reacts against the foreign antigens of the other individual (alloantigens) to cause rejection. The immune response to a transplanted organ is the consequence of a complex interplay between the innate and adaptive immune systems. Early ischemia-reperfusion injury to the allograft triggers an innate immune response and contributes to the activation of recipient T cells that recognize donor major and minor histocompatibility alloantigens.1 Once activated, T cells migrate into the allograft, where they mediate rejection by imposing direct cytotoxicity on allogeneic cells, or by providing help to other cells of the immune system, such as macrophages, natural killer (NK) cells, and B lymphocytes, which differentiate into antibody-producing cells. These effector cells and factors then lead to allograft injury.2 This review outlines the elements involved in the innate and adaptive immune responses to a transplant and the mechanisms of rejection.
Infections Following Transplantation
By Jessica M. Stempel, MD; Sophia Koo, MD; Nicholas C Issa, MDPurchase PDF
Infections Following TransplantationPurchase PDF
Infections following kidney transplantation are an important cause of morbidity and mortality throughout the entire posttransplantation period. Patients become more susceptible to an assortment of diverse infections following transplantation due to ongoing immunosuppression and may present with atypical clinical manifestations. An expeditious microbiologic workup and appropriate management are essential to ensure timely diagnosis and prompt initiation of specific therapy.
Histocompatibility Testing for Kidney Transplantation Risk Assessment
By Isabelle Lapointe, MD, FRCPC; Kathryn Tinckam, MD, MMSc, FRCPCPurchase PDF
Histocompatibility Testing for Kidney Transplantation Risk AssessmentPurchase PDF
Posttransplantation Malignancy in Kidney Transplant Recipients
By Marcelo S. Sampaio , MD PhD; Suphamai Bunnapradist , MD MSPurchase PDF
Posttransplantation Malignancy in Kidney Transplant RecipientsPurchase PDF
Surgical Aspects of Kidney Transplantation
By Anupamaa Seshadri, MD; Sayeed Malek, MDPurchase PDF
Surgical Aspects of Kidney TransplantationPurchase PDF
Kidney transplantation is the treatment of choice for patients with end-stage renal disease. This review discusses the surgical aspects of kidney transplantation in detail, beginning with the important features of the preoperative evaluation of a potential transplant recipient. We then explain in detail the technical aspects of living donor nephrectomy and kidney transplantation and provide guidance for managing variability in donor organ anatomy. Immediate postoperative management of the kidney transplant patient is briefly discussed. Finally, this review addresses the important postoperative complications to be aware of in the kidney transplant patient and management strategies, as well as outcomes of kidney transplantation.
Key words: chronic kidney disease, deceased donor transplantation, delayed graft function, kidney transplant, living donor nephrectomy, living donor transplantation, lymphocele, renal artery stenosis, transplant workup, urologic complications
National Kidney Allocation System
By William S Asch, MD, PhD; Darren Stewart, MS; Richard N Formica, MDPurchase PDF
National Kidney Allocation SystemPurchase PDF
Deceased donor kidneys for transplantation represent a scarce national resource. Therefore, allocation practices must be built on fair and equitable policies that ensure the best possible use of each kidney. The current kidney allocation policy was a decade in the making and required multiple rounds of public comment and revision to create a policy that balances utility and equity. The new allocation policy improves utility by maximizing life-years gained from kidney transplantation through longevity matching: pairing those patients with the longest expected life with kidneys expected to last the longest. It also, for the first time in kidney allocation, allocates kidneys based on need by prioritizing the highly sensitized patient and giving waiting time credit for time spent on dialysis prior to registration. Finally, the system attempts to both increase recovery and promote rapid placement of kidney from older donors. This is done through an opt-in system that attempts to allocate kidneys with a shorter duration of expected function and a higher Kidney Donor Profile Index to older recipients who would trade off a greater duration of function for more rapid transplantation. Coupled with the new allocation policy, the use of biopsy results from deceased donor grafts, characteristics of blood flow when placed on mechanical perfusion devices, and molecular biomarker measurement have the potential to expand the available pool of deceased donor kidneys. The new approach to kidney allocation in the United States provides a case study into how to thoughtfully and equitably distribute a scarce resource.
Acute Graft Dysfunction
By Oluwafisayo Adebiyi, MD; Alexander C. Wiseman, MD; James E. Cooper, MDPurchase PDF
Acute Graft DysfunctionPurchase PDF
Acute renal allograft dysfunction represents a spectrum of abnormalities that may be seen from the time of transplant surgery to eventual organ failure. Although renal allografts are often plagued by similar conditions as seen in native kidneys, they are also at risk for unique abnormalities specific to the transplant setting, such as delayed graft function (DGF), acute and chronic graft rejection, post-transplantation infections, and perinephric fluid collections.
This review contains 5 figures, 10 tables, and 94 references.
Keywords: Acute renal allograft dysfunction, delayed graft function, acute graft rejection, chronic graft rejection, perinephric fluid collections, post-transplantation infections
By Steven Gabardi, PharmD, BCPS, FAST, FCCP; Miae Kim, MS, PharmD, BCPSPurchase PDF
The primary objective of clinical immunosuppression following renal transplantation is to prevent rejection while limiting the toxicities of the immunosuppressive agents. A balance between over- and underimmunosuppression can be difficult to accomplish and has significant ramifications if not achieved. The major sequelae of underimmunosuppression are cellular and antibody-mediated allograft rejection, whereas overimmunosuppression can give rise to complications such as infection and malignancy. Local protocols and national/international guidelines have been established to aid in the streamlining of immunosuppressive regimens; however, the development of the most appropriate immunosuppressive therapy in an individual transplant recipient is highly dependent on a practitioner’s experience, preexisting medical conditions/medications, and donor characteristics. Despite the success seen by our individualized immunosuppressive regimens in improving short-term outcomes, late graft loss and the morbidity associated with long-term immunosuppression remain major concerns. To improve outcomes in renal transplantation, it is imperative that clinicians be aware of the specific advantages and disadvantages of the available immunosuppressants, as well as the potential for adverse drug reactions and drug-drug interactions commonly seen with these agents.
This review contains 5 figures, 5 tables and 92 references
Key Words: immunosuppression, pharmacodynamics, pharmacokinetics, renal transplantation
Chronic Allograft Dysfunction
By Juliya Hemmett, MD, FRCPC; Anthony M Jevnikar, MD, FRCPC, MSc; Lakshman Gunaratnam, MD, MScPurchase PDF
Chronic Allograft DysfunctionPurchase PDF
Premature renal allograft failure is a major problem in kidney transplantation as it is associated with high morbidity, mortality, and health care costs as patients return to dialysis. The most common cause of graft loss the first year after transplantation is death with a functioning graft, closely followed by what is now termed chronic allograft dysfunction (CAD). Development of donor-specific antibodies and chronic antibody rejection are emerging as the major pathophysiologic mechanisms responsible for this entity. There are currently no validated therapies for CAD, but improving adherence and reducing risk factors for CAD may improve outcomes. This review summarizes current understanding of the epidemiology, diagnosis, and pathophysiology of CAD, as well as potential treatment strategies.
This review contains 3 figures and 133 references
Medical Management of Transplant Patients
By Nelson B Goes, MD; Nidyanandh Vadivel, MB, BChPurchase PDF
Medical Management of Transplant PatientsPurchase PDF
Kidney transplant is the best form of renal replacement therapy for most end-stage kidney disease patients due to improved quality of life and superior patient survival compared to chronic maintenance dialysis. Long-term outcome of kidney allograft recipients depends on the longevity of the allograft and optimal management of their comorbidities such as cardiovascular disease risk factors. According to organ procurement and transplant data in the United States, 14.5% of the deceased donor kidney wait list comprised patients who failed their first allograft and were awaiting second kidney transplant. Optimal immunosuppression management is key to both short- and long-term outcomes of allograft transplant by preventing rejection while avoiding or minimizing risk of over immunosuppression such as with infections and neoplasia. Cardiovascular disease is the leading cause of mortality after kidney transplant. It accounts for approximately 50% of deaths in the post transplant period and 30% of deaths among patients with preserved renal allograft function. Hence, it is crucial to optimally manage cardiovascular risk factors such as hypertension and diabetes post transplant. In this chapter, we review medical management of kidney transplant recipients, including commonly used induction therapies, maintenance immunosuppressive agents, and posttransplant medical complications such as posttransplant diabetes mellitus, hypertension, cardiovascular disease, bone disease, and BK viral infection.
This review contains 1 table and 47 references
Key Words: kidney transplantation, immunosuppression, rejection, post transplant diabetes mellitus (PTDM), BK viral infection, calcineurin inhibitors,
- Chronic Kidney Disease
Approach to the Patient With Kidney Disease
By Mustafa Arici, MD, FERAPurchase PDF
Approach to the Patient With Kidney DiseasePurchase PDF
Chronic kidney disease (CKD) has diverse presentations that are frequently subclinical early in its course but symptomatic in more advanced stages. Quite commonly, kidney disease is diagnosed as an incidental finding in blood or urine tests. It is therefore crucial to understand how to assess kidney function tests and know the diverse presentations of kidney diseases in clinical practice. Assessment of kidney function mainly comprises three important steps: measuring glomerular filtration rate (GFR), estimation of urine albumin or protein excretion, and urinalysis/sediment examination. Estimating GFR based on a filtration marker (usually serum creatinine) is now widely accepted as the initial test. Several GFR prediction equations that use serum creatinine or other filtration markers along with certain patient characteristics (such as age, gender, and race) are used to estimate GFR, though several limitations must be considered when interpreting their results. Measurement of proteinuria or albuminuria provides insights into etiology (glomerular versus other parenchymal kidney diseases) and an assessment of risk of progression (ie, greater proteinuria, higher risk of progression). A complete examination of urine should be performed in all kidney patients. Urinalysis/sediment examination provides important information for both differential diagnosis of acute kidney disease (AKD) and CKD and clues for underlying etiologies of kidney disease. Several serologic tests and selected imaging studies complement the assessment of kidney diseases. Renal biopsy is occasionally required to specify the exact diagnosis and direct the treatment. All these investigations should be performed to determine the duration of kidney disease (ie, acute or chronic), designate the specific etiology, assess the risk for progression, and evaluate the presence of complications. Recently, several risk stratification scores or prediction models were developed for early diagnosis or predicting prognosis of acute kidney injury or CKD. These risk models may help to decrease the huge burden of kidney diseases on the individual as well as social level.
This review contains 1 figure, 11 tables and 29 references
Key Words: albumin-creatinine ratio, albuminuria, biomarkers, eGFR, chronic kidney disease, cystatin C, history, imaging, glomerular filtration rate , physical examination, renal biopsy, serum creatinine, urinalysis
Management of Chronic Kidney Disease and Its Complications
By Joshua S. Hundert, MD; Ajay K Singh, MBBS, FRCP (UK), MBAPurchase PDF
Management of Chronic Kidney Disease and Its ComplicationsPurchase PDF
Management of early renal failure helps in the reduction or prevention of end-stage renal disease. The monitoring of renal function is discussed, and the chapter includes a table that shows commonly used methods for monitoring. Risk factors for chronic renal failure include stroke and cardiac disease. Risk factors for renal disease progression are diabetes mellitus, hypertension, proteinuria, smoking, protein intake, and hyperlipidemia. Complications of chronic renal failure that are addressed include sodium and water imbalance, potassium imbalance, acidosis, calcium and phosphorus imbalance, and anemia. There is also a section that discusses the case for early referral to a nephrologist. Tables present the equations used to estimate the glomerular filtration rate (GFR); stages of chronic kidney disease and the appropriate steps in their management; risk factors for chronic kidney disease in which the testing of proteinuria and estimation of GFR are indicated; appropriate diet for patients who have chronic kidney disease; and guidelines for diagnosing and treating anemia resulting from chronic kidney disease. An algorithm outlines the steps in management of calcium and phosphate in patients with kidney disease.
This review contains 3 highly rendered figures, 6 tables, and 93 references.
Kidney Disease in Pregnancy
By Kavitha Vellanki, MD; Susan Hou, MDPurchase PDF
Kidney Disease in PregnancyPurchase PDF
Pregnancy-induced changes in renal hemodynamics play an important role in favorable maternal and fetal outcomes. Renal plasma flow and glomerular filtration rate (GFR) increase by approximately 50% in normal pregnancy, leading to a decrease in both blood urea nitrogen and serum creatinine when compared with prepregnancy levels. Hence, serum creatinine–based formulas are not accurate in calculating estimated GFR in pregnant patients. The most compelling risk for pregnant women with moderate to severe chronic kidney disease is the risk of rapid progression of underlying kidney disease; the mechanisms for such decline are yet to be elucidated. The rule of kidney disease not progressing when serum creatinine is less than 1.4 mg/dL does not apply to women with lupus nephritis. New-onset lupus is an indication for kidney biopsy during pregnancy because diffuse proliferative lupus nephritis requires prompt treatment and first-line treatments are teratogenic. Infertility is common in women on dialysis and is usually reversed after successful kidney transplantation. Pregnancy outcomes have improved over the years with increasing intensity of hemodialysis in end-stage kidney disease patients. Pregnancy post–kidney transplantation should be planned and teratogenic medications discontinued before conception.
Pharmacokinetic Principles of Drug Therapy in Chronic Kidney Disease Patients
By Joanna Q Hudson, PharmD, BCPS, FASN, FCCP, FNKFPurchase PDF
Pharmacokinetic Principles of Drug Therapy in Chronic Kidney Disease PatientsPurchase PDF
Pharmacokinetics (PK) describes the disposition of a drug in the body and is determined by the absorption, distribution, metabolism, and elimination of a drug. In patients with advanced kidney disease, changes in these processes may occur that affect drug disposition. Further complicating this issue is the fact that drug interactions and medication-related problems are also frequent as a result of altered PK and the high medication burden of the chronic kidney disease (CKD) population. Clinicians who manage patients with CKD and are responsible for drug prescribing and evaluation of the effectiveness and safety of prescribed medication regimens should have an understanding of the potential effect of CKD on drug disposition and the consequences if adjustment to dosing regimens is not made in response. They should also understand options for altering dosing regimens and the most rational approach based on the extent of kidney dysfunction and the specific medication prescribed.
Hematologic Abnormalities in Chronic Kidney Disease
By Khalid Al Talib, MD; Michael Auerbach, MD, FACP; John Anderson, MDPurchase PDF
Hematologic Abnormalities in Chronic Kidney DiseasePurchase PDF
The focus of this review is on information practical to the practicing nephrologist and internists managing patients with chronic kidney disease (CKD), with an emphasis on the quantitative aspects of risk, diagnosis, treatment, and prognosis. Consequently, anemia associated with non–dialysis-associated CKD is emphasized, with special attention to the role of erythropoiesis-stimulating agents and intravenous (IV) iron in treating the anemia of CKD, as well as sections on uremic bleeding and anticoagulation in CKD patients. Figures show a patient before and after a minor infusion reaction, an algorithm outlining grading and management of acute hypersensitivity reactions to IV iron infusions, and an algorithm for the management of uremic platelet dysfunction. Tables list Food and Drug Administration-recommended dose adjustments for novel oral anticoagulant (NOACs) in CKD patients, evidence for preprocedural withholding of NOACs, and management guidelines for anticoagulation in nonvalvular atrial fibrillation and venous thromboembolism.
This review contains 2 highly rendered figures, 3 tables, and 101 references.
Key words: Chronic kidney disease; CKD; Anemia of chronic kidney disease; Anemia of CKD; Uremic bleeding; Anticoagulation in CKD; Novel oral anticoagulants in CKD; NOAC CKD
- UTI, Pyelonephritis and Reflux Nephropathy
By Ita Pfeferman Heilberg, MD, PhD; José Luiz Nishiura, MD, PhDPurchase PDF
Nephrolithiasis is a highly prevalent condition, but its incidence varies depending on race, gender, and geographic location. Approximately half of patients form at least one recurrent stone within 10 years of the first episode. Renal stones are usually composed of calcium salts (calcium oxalate monohydrate or dihydrate, calcium phosphate), uric acid, or, less frequently, cystine and struvite (magnesium, ammonium, and phosphate). Calcium oxalate stones, the most commonly encountered ones, may result from urinary calcium oxalate precipitation on the Randall plaque, which is a hydroxyapatite deposit in the interstitium of the kidney medulla. Uric acid nephrolithiasis, which is common among patients with metabolic syndrome or diabetes mellitus, is caused by an excessively acidic urinary pH as a renal manifestation of insulin resistance. The medical evaluation of the kidney stone patient must be focused on identifying anatomic abnormalities of the urinary tract, associated systemic diseases, use of lithogenic drugs or supplements, and, mostly, urinary risk factors such as low urine volume, hypercalciuria, hyperuricosuria, hypocitraturia, hyperoxaluria, and abnormalities in urine pH that can be affected by dietary habits, environmental factors, and genetic traits. Metabolic evaluation requires a urinalysis, stone analysis (if available), serum chemistry, and urinary parameters, preferably obtained by two nonconsecutive 24-hour urine collections under a random diet. Targeted medication and dietary advice are effective to reduce the risk of recurrence. Clinical, radiologic, and laboratory follow-ups are needed to prevent stone growth and new stone formation, to assess treatment adherence or effectiveness to dietary recommendations, and to allow adjustment of pharmacologic treatment.
This review contains 5 highly rendered figure, 3 tables, and 105 references.
By Andre P Fay, MD; Pablo M Barrios; Fábio A B Schutz, MD; Carlos H Barrios, MDPurchase PDF
Kidney NeoplasiaPurchase PDF
The incidence of kidney cancer is rising. Due to the widespread use of abdominal imaging for unrelated indications, small renal masses have been increasingly detected incidentally. A better understanding of the biology underlying the different tumor types arising from the kidney cortex has opened new avenues to define diagnosis, prognosis, and treatment strategies. Complete surgical resection remains the standard approach to treat renal neoplasms, and no systemic treatments have proven to be effective after a curative intent surgery. Approximately 30 to 40% of patients with kidney cancer will experience recurrence after a definitive treatment and will ultimately succumb to their disease. Drugs targeting the vascular endothelial growth factor and mammalian target of rapamycin pathways have significantly changed the outcome of patients with metastatic renal cell carcinoma (mRCC). Recently, the new era of immunotherapy has brought a new breath to the treatment of mRCC and will integrate into the landscape of treatment, improving clinical outcome.
This review contains 3 figures, 7 tables and 129 references
Key words: benign kidney tumors, cystic renal mass, kidney cancer, kidney neoplasms, metastatic renal cell carcinoma, renal cell carcinoma, small renal masses
- Parenchymal Kidney Disease
Acute Interstitial Nephritis
By Dennis G. Moledina, MD; Mark A. Perazella, MDPurchase PDF
Acute Interstitial NephritisPurchase PDF
Rapidly Progressive Glomerulonephritis
By Stephen P McAdoo, MRCP PhD; Charles D. Pusey , FRCP DScPurchase PDF
Rapidly Progressive GlomerulonephritisPurchase PDF
Chronic Interstitial Nephritis
By Gearoid M McMahon, MBBChPurchase PDF
Chronic Interstitial NephritisPurchase PDF
Chronic interstitial nephritis is a progressive kidney disease with a wide variety of causes characterized by the presence of tubulointerstitial fibrosis, inflammation, and tubular atrophy. Most patients with advanced chronic kidney disease will have at least some degree of chronic interstitial nephritis present on a renal biopsy. However, there is a subset of renal diseases that specifically target the interstitium, leading to a progressive decline in kidney function. This review discusses the pathology and pathophysiology of chronic interstitial nephritis. In addition, common causes are reviewed, with a particular emphasis on recently described variants, including genetic causes of interstitial nephritis, Mesoamerican nephropathy, Balkan endemic nephropathy, and IgG4-related kidney disease.
Key words: Chronic Kidney Disease, Inflammation, Fibrosis,
The Primary Glomerular Diseases
By Richard J. Glassock, MD, MACP; Sanjeev Sethi, MD, PhD; Fernando C. Fervenza, MD, PhDPurchase PDF
The Primary Glomerular DiseasesPurchase PDF
Glomerular disorders in which the manifestations of disease are primarily confined to the kidneys, without multisystem involvement, are not only common but very heterogeneous in terms of pathogenesis and clinical features. Typically, these primary glomerular diseases are characterized according to the findings on renal biopsy, as studied by light, immunofluorescence, and electron microscopy. The principal primary glomerular diseases are minimal change disease, focal and segmental glomerulosclerosis, membranous nephropathy, C3 glomerulonephritis and dense deposit disease, IgA nephropathy, and renal-limited crescentic glomerulonephritis. These clinicopathologic entities are discussed according to epidemiology, clinical features, pathology, pathogenesis (and genetics if appropriate), prognosis, and treatment, emphasizing recent findings.
Key words: C3 glomerulonephritis, dense deposit disease, focal and segmental glomerulosclerosis, glomerulonephritis, IgA nephropathy, membranous nephropathy, minimal change disease, renal biopsy, renal-limited crescentic glomerulonephritis
By Kar Neng Lai, MD, DSc, FRCP, FRACP, FRCPath; Andrew SH Lai, MBBS, FRCR; Sydney CW Tang, MD, PhD, FRCPPurchase PDF
Viral NephropathiesPurchase PDF
Viral infections are important causative agents in renal disease and are responsible for significant morbidity and mortality. The diagnostic criteria for virus-related nephropathy include detailed clinical and laboratory data and tissue molecular analysis. Possible pathogenetic mechanisms include kidney tropism of the virus, induction of abnormal immune complexes, direct cytopathogenic effects, and multiorgan failure. Hepatitis B virus is associated with membranous nephropathy and mesangiocapillary glomerulonephritis in endemic areas. Hepatitis C virus causes various forms of glomerulonephritis, including cryoglobulinemia-mediated glomerulonephritis. HIV infection is associated with a collapsing focal segmental glomerulosclerosis, a distinctive disease that mainly affects Africans and African Americans. In the course of HIV infection, other types of immune complex glomerulonephritis may occur. Recent reports indicate a role for parvovirus B19 in idiopathic collapsing focal segmental glomerulosclerosis. Acute kidney injury occurs in hantavirus and coronavirus-associated severe acute respiratory syndrome. Of particular interest are those viral infections with productive replication in the kidney, which often occur in immunocompromised hosts, such as renal allograft recipients. Epstein-Barr virus, cytomegalovirus, adenovirus, and BK polyomavirus are prominent members of this group causing specific diseases. Renal biopsy followed by appropriate serologic and molecular testing is essential for defining virus-related nephropathies and guiding prognostic and therapeutic evaluation.
This review contains 4 figures, 3 tables, and 90 references.
Key words: BK polyomavirus, cytomegalovirus, glomerulonephritis, hepatitis B, hepatitis C, HIV-associated nephropathy, viral infection
Paraproteinemia and Deposition Diseases
By Insara Jaffer Sathick, MBBS, MRCP; Nelson Leung, MDPurchase PDF
Paraproteinemia and Deposition DiseasesPurchase PDF
The kidney is often involved in diseases associated with monoclonal proteins. In large part, this is due to the physiology and glomerular architecture leading to interactions between the monoclonal proteins and nephron. A variety of pathologic lesions have been described in the kidney as a result of monoclonal immunoglobulins. The spectrum of kidney diseases associated with plasma cell dyscrasias is quite broad and involves almost the entire nephron. This is due to the different types of monoclonal proteins (light chain, heavy chain, and entire immunoglobulin), the highly variable nature of immunoglobulins, and the diversity of paraproteinemias themselvesIt is important for the nephrologist to recognize these conditions because the treatment of plasma cell dyscrasias has vastly improved over the past decade. This chapter discusses myeloma cast nephropathy, amyloidosis, and other glomerulopathies. Figures show paraproteinemia-associated kidney disease, and an algorithm for the typing of amyloidosis. Tables list a classification of amyloidosis affecting the kidney, distinguishing features of diseases with organized deposits, and classification of cryoglobulinemia.
This review contains 2 figures, 3 tables, and 105 references.
Key words: myeloma cast nephropathy, amyloidosis, glomerulopathies, monoclonal immunoglobulins, monoclonal proteins, monoclonal gammopathy of undetermined significance, MGUS, monoclonal gammopathy of renal significance, MGRS
Approach to the Patient With Glomerular Disease
By Richard J. Glassock, MD, MACP; An S De Vriese, MD, PhD; Fernando C. Fervenza, MD, PhDPurchase PDF
Approach to the Patient With Glomerular DiseasePurchase PDF
Glomerular diseases of the kidneys are associated with a limited array of clinical syndromes, including asymptomatic hematuria and/or proteinuria, acute nephritis, nephrotic syndrome, rapidly progressive glomerulonephritis, and chronic glomerulonephritis. The specific diseases that underlie these syndromes are numerous and heterogeneous. Broadly, they may be divided into primary and secondary disorders depending on whether the kidneys are the sole organs affected or whether other organ systems are also involved in the disease processes. A systematic approach involving a careful history, physical examination, assessment of renal function, and urinalysis (composition and microscopy) and protein excretion, combined with biochemical and serologic testing, can provide important clues to diagnosis and prognosis. Renal biopsy is often required for a complete and accurate diagnosis as well as a prognosis and therapeutic decision making.
This review contains 4 figures, 6 tables and 92 references
Key words: glomerular filtration rate, glomerulonephritis, hematuria, nephrotic syndrome, proteinuria, renal biopsy, serum complement
Nutritional Support in Acute Kidney Injury
By Alice Sabatino , RD, MSc; Giuseppe Regolisti , MD; Filippo Fani , MD; Enrico Fiaccadori, MD, PhDPurchase PDF
Nutritional Support in Acute Kidney InjuryPurchase PDF
Protein-energy wasting (PEW) is particularly common in patients with acute kidney injury (AKI). It is correlated, at least in part, with specific factors of the reduction of renal function and is associated with significant increase in mortality and morbidity. In this clinical condition, the optimal nutritional support remains an open question due to its qualitative composition in terms of macro- and micronutrients. In fact, data on critically ill patients have confirmed that nutritional support targeting the real protein and energy needs is associated with improvement of clinical outcome. However, data available in AKI patients are still scarce. AKI is characterized by increased risk of both under- and overfeeding because of the coexistence of many factors that can influence the evaluation of nutrient needs, such as a rapid change in body weight due to alterations in fluid balance, loss of nutrients during renal replacement therapy (RRT), and the presence of hidden calories in the RRT (ie, calories derived from anticoagulants and/or from solutions used in the different dialysis methods). As AKI comprises a highly heterogeneous group of patients, with oscillatory nutrient needs during patients’ clinical course, nutritional requirements should be frequently reassessed, individualized, and carefully integrated with RRT. Nutrient needs in patients with AKI can be difficult to estimate and should be directly measured, especially in the intensive care unit setting.
This review contains 4 figures, 3 tables and 104 references
Keywords: Malnutrition In ICU Patients, Acute Kidney Injury, Nutritional Support, Indirect Calorimetry, Resting Energy Expenditure, Lipid Oxidation Rate, Glucose Oxidation Rate, Micronutrients
- Acute Kidney Injury
Epidemiology of Acute Kidney Injury
By Verônica Torres Costa e Silva, MD, PhD; Renato Antunes Caires, MD; Elerson Carlos Costalonga, MD; Emmanuel A. Burdmann, MD, PhDPurchase PDF
Epidemiology of Acute Kidney InjuryPurchase PDF
The worldwide incidence of acute kidney injury (AKI) is increasing. Recent surveys demonstrated that AKI occurs in 21% of hospital admissions. In low-income countries, AKI has a bimodal presentation. In large urban centers, the pattern of AKI is very similar to that found in high and upper middle-income countries, with a predominance of hospital-acquired AKI, occurring mostly in older, critically ill, multiorgan failure patients with comorbidities. At the same time, in regional hospitals in small urban communities and rural areas, AKI is usually a community-acquired disease (related to diarrheal and infectious diseases, animal venom, and septic abortion). Although AKI mortality seems to be decreasing, it remains extremely high, varying from 23.9 to 60% in recent series. The most important risk factors for short-term mortality (in hospital or < 90 days) in AKI are the primary diagnosis (sepsis) and the severity of the acute illness, expressed by the presence of nonrenal organ dysfunction. New biomarkers, such as urinary neutrophil gelatinase-associated lipocalin, cystatin C, and interleukin-18 measurements, have been able to identify patients with AKI who are at risk for a less favorable prognosis, such as the likelihood of the need for renal replacement therapy, nonrecovery of kidney function, and higher mortality. Several studies have demonstrated an association between hospital-associated AKI and postdischarge mortality in a variety of contexts, and the most important risk factors for this late lethality are older age, preexisting comorbid disease (chronic kidney disease [CKD], cardiovascular disease, or malignancy), and incomplete organ recovery with ongoing residual disease. AKI is associated with de novo end-stage renal disease (ESRD) (CKD, progression of preexisting CKD) and the occurrence of ESRD in the long term. Herein, it is suggested that high-risk patients recovering from an AKI episode, such as those with baseline CKD, diabetes mellitus, or heart failure and those dialyzed for AKI, should likely be followed by a nephrologist.
Pathophysiology of Acute Kidney Injury
By Shalini Bumb, MD; Andrew Malone, MB, BCh; Matthew A. Sparks, MDPurchase PDF
Pathophysiology of Acute Kidney InjuryPurchase PDF
Acute kidney injury (AKI) is defined as the abrupt loss of kidney excretory function with the accumulation of nitrogenous waste products and fluid overload. The etiologies of AKI are numerous and can largely be classified as prerenal, intrinsic, or postrenal. Complex pathways involving inflammatory mediators, vascular compromise, and direct cellular injury are triggered, and equally as complex pathways, including autophagy and fibrosis, are involved in the recovery. Prerenal azotemia is caused by a reduction in tissue perfusion with resulting AKI. Although acute tubular necrosis is the most common intrinsic etiology, other nephrotoxins and exposures can result in intrinsic injury as well. Postrenal AKI is due to obstruction of urinary flow. Herein, in further detail, the mechanisms, pathophysiology, and manifestations of these causes of AKI are discussed. Research into the mechanisms and development of markers and techniques to advance clinical practice is ongoing.
Drug Dosing in Acute Kidney Injury
By Steven Gabardi, PharmD, BCPS, FAST, FCCP; Marjan Sadegh, PharmD, BCPS; Craig A Stevens, PharmD, BCPS; Jamil Azzi, MDPurchase PDF
Drug Dosing in Acute Kidney InjuryPurchase PDF
The prevalence of acute kidney injury (AKI) among hospitalized patients has increased sharply over the past 10 to 20 years. One complicating factor in this population is that many pharmacologic agents that are administered to these patients are handled, to some degree, by the kidneys. These medications may experience altered pharmacokinetic and pharmacodynamic profiles in patients with renal dysfunction, increasing the chances of drug misadventures. Historically, drug dosing in patients with AKI has been approached in the same manner as in patients with chronic renal insufficiency (CRI). The majority of dosing recommendations for AKI have been extrapolated from studies performed in patients with stable CRI. Renal drug clearance, composed of glomerular filtration, tubular secretion, and renal drug metabolism, is affected by renal dysfunction. It is clear that there is a reduction in renal clearance of drugs and toxins in both AKI and CRI. However, the type of renal dysfunction may affect other parameters of drug handling. Thus, dosing stratagems extrapolated from patients with CRI may result in subtherapeutic drug concentrations and ineffective treatment. Achieving a balance between under- and overdosing requires rigorous monitoring and individualized dosing.
Key words: acute kidney injury, drug dosing, pharmacokinetics
Definitions, Classification, and Screening of Acute Kidney Injury
By Andrew Davenport, MDPurchase PDF
Definitions, Classification, and Screening of Acute Kidney InjuryPurchase PDF
Acute kidney injury (AKI; previously acute renal failure) is defined as an acute and sustained deterioration in kidney function. As AKI is a descriptive term, an attempt should be made to establish a diagnosis in patients with AKI. There are numerous causes of AKI, and all or part of the kidney may be affected. This review discusses the definitions of AKI, measurement of renal function, incidence of AKI, baseline serum creatinine, grading and severity of AKI, and screening for AKI. Figures show renal reserve and renal tubule. Tables list consensus definitions of AKI, effect of patient demographics on serum creatinine concentration, endogenous compounds that can interfere with colorimetric modified Jaffe-based reactions for determining serum creatinine concentration, risk factors for developing AKI in adult patients proposed by the Renal Angina Index, and risk factors for developing acute contrast-induced kidney injury in adult patients.
Key Words: Acute kidney injury; Acute renal failure; Glomerular filtration rate; Serum creatinine; Kidney function; Estimated glomerular filtration rate; Biomarkers of AKI
Acute Kidney Injury in the Cancer Patient
By Shveta Motwani, MD, MMSc, FASN; Albert Q. Lam, MDPurchase PDF
Acute Kidney Injury in the Cancer PatientPurchase PDF
Acute kidney injury (AKI) is a problem frequently encountered in patients with cancer that significantly impacts their well-being and outcomes. In addition to the usual prerenal, intrarenal, and postrenal etiologies of AKI, patients with cancer experience unique causes of AKI. Nephrologists caring for this population must be able to identify and manage these conditions, which often require distinguishing between causes resulting from the cancer itself and those related to chemotherapeutic or other concurrent treatment, to institute appropriate preventive or therapeutic strategies. In this review, we present a suggested systematic approach to the diagnosis of AKI in patients with cancer and discuss common clinical scenarios specific to this patient population, with a special emphasis on tumor infiltration of the kidney parenchyma, myeloma-related AKI, tumor lysis syndrome, thrombotic microangiopathy, AKI in the patient with hematopoietic stem cell transplantation, and renal disease in patients with renal cell carcinoma. We cover the latest evidence-based strategies for management of these disorders in this evolving field. In addition, we provide an updated table of potentially nephrotoxic chemotherapeutic agents with their associated mechanisms of kidney injury as a reference for clinicians to build on as they encounter the ever-expanding list of oncologic agents in practice. As the subspecialty of onconephrology continues to evolve, it will be increasingly important for clinicians to have the skills to effectively diagnose and treat AKI in cancer patients to minimize morbidity and mortality, decrease the incidence of subsequent chronic kidney disease, and maintain chemotherapeutic options for these patients.
This review contains 5 figures, 5 tables, and 61 references.
Key words: acute kidney injury, cancer, chemotherapy, onconephrology, renal failure
Conservative Management of Acute Kidney Injury
By Rolando Claure-Del Granado, MD, FASN; Etienne Macedo, MD, PhD; Ravindra L. Mehta, MD, FASNPurchase PDF
Conservative Management of Acute Kidney InjuryPurchase PDF
Acute kidney injury (AKI) is one of the most common complications occurring among intensive care unit (ICU) patients and is independently associated with a higher risk of mortality. In critically ill patients, AKI presentation is heterogeneous, varying from asymptomatic elevations in serum creatinine to the need for dialysis in the context of multiorgan failure. Within this range of clinical presentation, the kidney is often overlooked because improving and maintaining cardiac performance are the focus. In addition, aggressive fluid resuscitation may impose significant demands on the kidney wherein the normal excretory capacity may be overwhelmed. ICU patients often have underlying comorbidities, including chronic kidney disease and heart failure, which further limit the range of renal capacity. Drug and nutritional administration contribute to the demand for fluid removal to maintain fluid balance. The dissimilarities of the critical care environment and the extra demand kidney capacity highlight the need for different strategies for management and treatment of AKI in the critically ill patients. We focus this review on the general and nondialytic therapy of AKI.
This reference contains 5 figures, 3 tables and 90 references
Key words: Acute kidney injury, fluid resuscitation, loop diuretics, vasoactive agents, fluid overload, hiperkalemia, and metabolic acidosis.
- Dialytic Therapies
Management of Cardiovascular Disease in Dialysis Patients
By John K. Roberts ; John P. MiddletonPurchase PDF
Management of Cardiovascular Disease in Dialysis PatientsPurchase PDF
Cardiovascular disease is a common cause of death and disease in patients with end-stage renal disease (ESRD). Registry data show that 41% of deaths in ESRD patients are due to a variety of cardiovascular causes, such as acute myocardial infarction, congestive heart failure, arrhythmia/sudden cardiac death, and stroke. In the general population, each of these disease entities in isolation can be effectively managed according to evidence from large clinical trials and evidence-based guidelines. However, many of these trials did not include patients with ESRD, limiting the transferability of this evidence to the care of patients on dialysis. To complicate matters, cardiovascular events in ESRD patients are likely augmented from a unique interplay of cardiac risk due to both reduced kidney function and the necessity for artificial renal replacement therapies. In this light, the patient on dialysis is subjected to a series of unique factors: the continued presence of the metabolic perturbations of uremia and the peculiar environment of the dialysis treatment itself. Since the ESRD heart is under a considerable amount of strain due to chronic volume overload, rapid electrolyte and fluid shifts, and accelerated vascular calcification, management can be complex and outcomes multifactorial. In this review, we summarize the current evidence regarding management of acute myocardial infarction, heart failure, sudden cardiac death, and atrial fibrillation. We also address modifiable risk factors related to the dialysis procedure itself and highlight recent randomized controlled trials that included dialysis patients and measured important cardiovascular outcomes.
By François Madore, MD, MScPurchase PDF
Plasmapheresis has been applied over the last several decades as primary or adjunctive treatment for a number of primary renal diseases and systemic conditions with renal involvement. The present review discusses renal conditions for which plasmapheresis may be attempted with recommendations based on evidence from the literature. Other indications of special interest for renal physicians (e.g., sepsis and multiple organ failure, drug overdose, and poisoning) are also discussed. In addition, the present text reviews general apheresis principles, technical considerations for optimal plasmapheresis prescription, and possible complications of plasmapheresis. Knowledge of disease mechanisms and plasmapheresis principles is invaluable in applying a plasmapheresis treatment regimen appropriately.
Strategies of Hemodialysis Access
By Robyn A. Macsata, MD, FACS; Anton N. Sidawy, MD, MPH, FACSPurchase PDF
Strategies of Hemodialysis AccessPurchase PDF
Chronic kidney disease and end-stage renal disease (ESRD) have become common diagnoses in the United States; in response, several clinical practice guidelines for the surgical placement and maintenance of arteriovenous (AV) hemodialysis access have been published. This review examines temporary hemodialysis access, permanent hemodialysis accesses, and the Hemodialysis Reliable Outflow (HeRO) graft. Figures show trends in the number of incident cases of ESRD, in thousands, by modality, in the US population, 1980 to 2012, Medicare ESRD expenditures, algorithm for access location selection, autogenous posterior radial branch-cephalic wrist direct access (snuff-box fistula), autogenous radial-cephalic wrist direct access (Brescia-Cimino-Appel fistula), autogenous radial-basilic forearm transposition, prosthetic radial-antecubital forearm straight access, prosthetic brachial (or proximal radial) antecubital forearm looped access, autogenous brachial (or proximal radial) cephalic upper arm direct access, autogenous brachial (or proximal radial) basilic upper arm transposition, prosthetic brachial (or proximal radial) axillary (or brachial) upper arm straight access, prosthetic superficial femoral-femoral (vein) lower extremity straight access and looped access, prosthetic axillary-axillary (vein) chest looped access, straight access, and body wall straight access, HeRO graft, banding of the outflow access tract, distal revascularization with interval ligation, upper extremity edema and varicosities associated with venous hypertension, internal jugular to subclavian venous bypass, and puncture-site pseudoaneurysms of an AV access. Tables list AV access configuration, autogenous AV access patency rates, and prosthetic AV access patency rates.
This review contains 19 highly rendered figures, 3 tables, and 67 references
Complications of Arteriovenous Hemodialysis Access
By Thomas S. Huber, MD, PhDPurchase PDF
Complications of Arteriovenous Hemodialysis AccessPurchase PDF
Maintaining hemodialysis (HD) access represents a significant proportion of the workload for most general and vascular surgeons, and this burden is anticipated to increase. The number of remedial procedures is significant and it is incumbent upon all access surgeons to be familiar with the access-related complications outlined in the review. Failing and thrombosed access, access-related hand ischemia (ARHI) or steal, aneurysms and pseudoaneurysms, infection, central vein stenoses and occlusions, bleeding/hematoma, and seroma are discussed. Tables describe potential etiologies of autogenous arteriovenous HD access (AVF) failure to mature and presentations of the failing access, plus clinical risk factors and treatment options for ARHI. Figures show brachial-cephalic AVF, nonmaturing AVF, failing prosthetic arteriovenous HD access (AVG), endovascular treatment of thrombosed AVG, open surgical revision of thrombosed brachial-axillary AVG, arterial pressures and doppler waveforms, proximalization of the arterial inflow, distal revascularization and interval ligation, aneurysmal degeneration, AVG with fluid surrounding the access, central vein stenosis, and a treatment algorithm for ARHI.
This review contains 12 figures, 4 tables, and 79 references.
- Fluids and Electrolytes
By Lisa Cohen; Dipal Savla; Shuchi AnandPurchase PDF
Metabolic AcidosisPurchase PDF
Metabolic acidosis is a common clinical entity that can arise from a variety of disease states, medications, and toxic ingestions. This review covers the pathophysiology, diagnosis, and management of common presentations of metabolic acidosis. We have differentiated various causes of metabolic acidosis based on the presence of a normal or elevated anion gap (AG), the sum of serum anions unaccounted for by the measurement of plasma sodium, bicarbonate, and chloride levels. Normal AG metabolic acidosis, or non-AG metabolic acidosis, arises when there is excessive loss of bicarbonate from the gastrointestinal tract or in the urine. This review covers the development and diagnosis of non-AG metabolic acidosis, including a discussion of the spectrum of renal tubular acidosis subtypes. The treatment of non-AG metabolic acidosis is reviewed. Metabolic acidosis with an elevated AG, also called AG metabolic acidosis, develops when exogenous or endogenous nonchloride acid accumulates in the body. The most common causes of AG metabolic acidosis are lactic acidosis and ketoacidosis from starvation, heavy alcohol intake, or diabetes with total body insulin depletion. Medications, toxic substances, and uremia can also lead to AG acidosis. The mechanisms and management of these causes of metabolic acidosis with high AG are covered in detail.
Key words: anion-gap acidosis, diabetic ketoacidosis, lactic acidosis, non–anion gap acidosis
Approach to Acid-base Disorders
By Horacio J Adrogué, MD; Nicolaos E Madias, MDPurchase PDF
Approach to Acid-base DisordersPurchase PDF
This review on the approach to acid-base disorders uses the physiologic approach to assessing acid-base status, namely that based on the H2CO3/[HCO3–] buffer pair. A simple acid-base disorder is characterized by a primary abnormality in either carbon dioxide tension (Pco2) or serum [HCO3–] accompanied by the appropriate secondary response in the other component. The four cardinal, simple acid-base disorders are categorized into respiratory disorders and metabolic disorders. Respiratory disorders are expressed as primary changes in Pco2 and include respiratory acidosis or primary hypercapnia (primary increase in Pco2) and respiratory alkalosis or primary hypocapnia (primary decrease in Pco2). Metabolic disorders are expressed as primary changes in serum [HCO3–]) and include metabolic acidosis (primary decrease in serum [HCO3–]) and metabolic alkalosis (primary increase in serum [HCO3–]). A mixed acid-base disorder denotes the simultaneous occurrence of two or more simple acid-base disorders. Arriving at an accurate acid-base diagnosis rests with assessment of the accuracy of the acid-base variables, calculation of the serum anion gap, and identification of the dominant acid-base disorder and whether a simple or mixed disorder is present. Identifying the cause of the acid-base disorder depends on a detailed history and physical examination as well as obtaining additional testing, as appropriate.
Key words: acid-base disorders; simple disorders; mixed disorders; anion gap; physiologic approach; physicochemical approach; base-excess approach
Disorders of Water Balance
By Richard H Sterns, MD, FACP; Stephen M. Silver, MD; John K. Hix, MD; Jonathan W. Bress, MDPurchase PDF
Disorders of Water BalancePurchase PDF
Guided by the hypothalamic antidiuretic hormone vasopressin, the kidney’s ability to conserve electrolyte–free water when it is needed and to excrete large volumes of water when there is too much of it normally prevents the serum sodium concentration from straying outside its normal range. The serum sodium concentration determines plasma tonicity and affects cell volume: a low concentration makes cells swell, and a high concentration makes them shrink. An extremely large water intake, impaired water excretion, or both can cause hyponatremia. A combination of too little water intake with too much salt, impaired water conservation, or excess extrarenal water losses will result in hypernatremia. Because sodium does not readily cross the blood-brain barrier, an abnormal serum sodium concentration alters brain water content and composition and can cause serious neurologic complications. Because bone is a reservoir for much of the body’s sodium, prolonged hyponatremia can also result in severe osteoporosis and fractures. An understanding of the physiologic mechanisms that control water balance will help the clinician determine the cause of impaired water conservation or excretion; it will also guide appropriate therapy that can avoid the life-threatening consequences of hyponatremia and hypernatremia.
Respiratory Acidosis and Alkalosis
By Horacio J Adrogué, MD; Nicolaos E Madias, MDPurchase PDF
Respiratory Acidosis and AlkalosisPurchase PDF
Respiratory acid-base disorders are those disturbances in acid-base equilibrium that are expressed by a primary change in CO2 tension (Pco2) and reflect primary changes in the body’s CO2 stores (i.e., carbonic acid). A primary increase in Pco2 (and a primary increase in the body’s CO2 stores) defines respiratory acidosis or primary hypercapnia and is characterized by acidification of the body fluids. By contrast, a primary decrease in Pco2 (and a primary decrease in the body’s CO2 stores) defines respiratory alkalosis or primary hypocapnia and is characterized by alkalinization of the body fluids. Primary changes in Pco2 elicit secondary physiologic changes in plasma [HCO3ˉ] that are directional and proportional to the primary changes and tend to minimize the impact on acidity. This review presents the pathophysiology, secondary physiologic response, causes, clinical manifestations, diagnosis, and therapeutic principles of respiratory acidosis and respiratory alkalosis.
This review contains 4 figures, 3 tables, and 59 references.
Key words: Respiratory acidosis, respiratory alkalosis, primary hypercapnia, primary hypocapnia, hypoxemia, pseudorespiratory alkalosis
By Fouad T Chebib, MDPurchase PDF
Metabolic AlkalosisPurchase PDF
Metabolic alkalosis is a common clinical problem encountered by the nephrologist. An understanding of the pathogenesis of this electrolyte disorder, which includes a generative and a maintenance phase, is essential to elucidating the etiology and deciding on the appropriate treatment. Metabolic alkalosis is characterized by an increase in pH, a decrease in [H+], and an increase in [HCO3–]. The generative phase of metabolic alkalosis involves either loss of acid (e.g., gastrointestinal losses), gain of bicarbonate (e.g., antacids), or cellular shift (e.g., hypokalemia). The maintenance phase involves impairment of the renal handling of bicarbonate (decreased glomerular filtration, increased bicarbonate tubular reabsorption). We discuss the different etiologies, such as chloride depletion (e.g., vomiting), potassium depletion (e.g., primary hyperaldosteronism), and hypercalcemic states (e.g., milk-alkali syndrome). This review also discusses the symptoms, diagnosis, and prognosis of metabolic alkalosis. A diagnostic algorithm based on volume status and urine electrolytes will help differentiate the different etiologies. Treatment options are summarized based on chloride-sensitive or chloride-resistant metabolic alkalosis.
This review contains 5 figures, 3 tables and 12 references
Key words: chloride resistance, chloride sensitivity, generative phase, maintenance phase, metabolic alkalosis, syndromes with metabolic alkalosis
- Genetics and the Kidney
Cystic Diseases of the Kidney
By Christian Riella, MD; Peter G Czarnecki, MD; Theodor I Steinman, MDPurchase PDF
Cystic Diseases of the KidneyPurchase PDF
The spectrum of cystic kidney diseases encompasses a wide range of genetic syndromes with different identified disease genes, modes of inheritance, extrarenal organ manifestations, and clinical progression. Depending on the given disease gene and type of mutation in a respective cystic kidney disease, the age of onset, pathologic characteristics, and rate of progression to end-stage kidney disease vary considerably. This review covers disease definitions, etiology and genetics, pathophysiology and pathogenesis, diagnosis, differential diagnosis, and treatment of cystic kidney disease. Additionally, simple and complex renal cysts in adults are discussed. Tables list the epidemiology of polycystic kidney disease, gene locus, and encoded protein, unified criteria for ultrasonographic diagnosis of autosomal dominant polycystic kidney disease (APDKD), risk factors for progressive kidney disease in APDKD, differential diagnosis of cystic diseases of the kidney, Halt Progression of Polycystic Kidney Disease trial summary, and other extrarenal manifestations of ADPDK.
Key Words: Cystic kidney disease; Autosomal dominant polycystic kidney disease; APDKD; Polycystic kidney disease; PKD; End-stage renal disease; Renal cysts; Progressive kidney disease
Inherited Proximal and Distal Renal Tubular Acidosis
By Daniel Batlle, MD; Patricia Valles, MD; Jesus Moran-Farias, MDPurchase PDF
Inherited Proximal and Distal Renal Tubular AcidosisPurchase PDF
Acid-base homeostasis by the kidney is maintained through proximal tubular reclamation of filtered bicarbonate and the excretion of the daily acid load by collecting duct type A intercalated cells. The impairment of either process results in renal tubular acidosis (RTA), a group of disorders characterized by a reduced net acid excretion and a persistent hyperchloremic, non–anion gap metabolic acidosis. The primary or hereditary forms of proximal (pRTA) and distal renal tubular acidosis (dRTA) have received increased attention because of advances in the understanding of the molecular mechanism, whereby mutations in the main proteins involved in acid-base transport result in either reduced bicarbonate reabsorption or reduced H+ secretion and impaired acid excretion. dRTA is characterized by reduced net acid excretion and an inability to lower urine pH despite severe acidemia (but minimal HCO3– wastage). pRTA (type 2), by contrast, is characterized by marked HCO3– wastage but preserved ability to lower urine pH when plasma HCO3– (and therefore filtered HCO3–) is below a certain threshold. In children with dRTA, growth retardation caused by chronic metabolic acidosis is the key manifestation but is fully reversible with appropriate alkali therapy if initiated early in life. A striking manifestation of many patients with dRTA is the development of severe hypokalemia that may cause muscle paralysis. In this review, we discuss these types of hereditary RTA and the mechanisms involved in the genesis of these inherited tubular disorders.
This review contains 5 figures, 1 table, and 103 references.
Key words: Proximal renal tubular acidosis (pRTA), Distal renal tubular acidosis (dRTA), Hyperchloremic, non–anion gap metabolic acidosis, Hypokalemia, Fractional HCO3– excretion, Urinary gap, Fanconi Syndrome.ATP6V1B1 and ATP6V0A4 gene mutations . Intercalated cells ,
- Hypertension and the Kidney
Hypertensive Disorders in Pregnancy
By Kavitha Vellanki, MD; Susan Hou, MDPurchase PDF
Hypertensive Disorders in PregnancyPurchase PDF
Hypertensive disorders are the second leading cause of maternal mortality in the United States. Hypertension in pregnancy is defined as blood pressure greater than or equal to 140 mm Hg systolic or greater than or equal to 90 mm Hg diastolic, measured on at least two separate occasions. Preeclampsia, as per the new guidelines, is characterized by the new onset of hypertension and either proteinuria or other end-organ dysfunction, more often after 20 weeks of gestation in a previously normotensive pregnant woman. New-onset proteinuria is not required for diagnosis of preeclampsia if there is evidence of other end-organ damage—a change from previous classifications. Although no screening test has yet proven accurate enough to predict preeclampsia, the use of a combination of the serologic factors seems promising. There are few data to support any specific blood pressure target in pregnancy. Although there is a general consensus on treating severe hypertension in pregnancy, there is a difference of opinion on treating mild to moderate hypertension in pregnancy. Avoiding uteroplacental ischemia and minimizing fetal exposure to adverse effects of medications are as important as avoiding maternal complications from high blood pressure during pregnancy.
This review contains 2 figures, 4 tables, and 73 references.
Genetics of Hypertension
By Paul J Phelan, MB BCh BAO, MD, FRCP (Edin); Matthew A. Sparks, MDPurchase PDF
Genetics of HypertensionPurchase PDF
Despite the high prevalence of hypertension and its resulting morbidity and mortality, our knowledge of its pathogenesis remains limited. Strong evidence for a genetic role in blood pressure (BP) variability was first provided by familial segregation studies and the identification of mendelian disorders causing marked hypertension. These monogenic diseases, largely involving genes in sodium homeostatic pathways, have reinforced the Guytonian principle that BP is largely governed by renal sodium excretion. More recently, large population based genome wide association studies (GWAS) have attempted to fill in the missing heritability of the BP trait, with mixed results. Although many variants have been identified that are robustly associated with BP variability, they are mostly rare and together are responsible for a tiny percentage of total trait variability. Observations from GWAS include shared risk variants for cardiovascular and kidney disease, including polymorphisms in UMOD. Mutations in this gene are known to cause monogenic renal disease. GWAS data may be employed for pathway analysis to discover the etiology of hypertension as well providing the potential to interrogate drug responses to antihypertensive agents depending on genotype. The chapter concludes with describing future directions in BP genetics including evidence of the role of epigenetic mechanisms in BP pathogenesis. As we enter the era of whole genome sequencing, the possibility exists to discover the missing hereditability of BP variation although this technology will present its own challenges.
This review contains 6 figures, 2 tables and 94 references
Key words: adrenocorticotropic hormone, autosomal dominant, autosomal recessive, cytosine-phosphate-guanine, epithelial sodium channel