Cardiorenal Syndrome

Renal and cardiac crosstalk plays an essential role in maintaining physiological homeostasis. Both organ diseases are prevalent and share common risk factors. Impairment in one organ has the potential to affect the other. This interaction is referred to as cardiorenal syndrome, and it is driven by complex neurohumoral and vascular processes. Cardiorenal syndrome refers to a state of either acute or chronic impairment of both renal and cardiac functions. Despite progress in therapeutic interventions, treatment of cardiorenal syndrome remains challenging. In this chapter, we review the current understanding of the pathophysiological mechanisms of cardiorenal syndrome, as well as its management options.

Hepatitis-Associated Glomerulonephritis

Viral hepatitis can be associated with extrahepatic manifestations, including kidney injury, mainly glomerulonephritis (GN). The physiopathology of GN is of particular interest because some immune responses, triggered by viral infections, can harm the glomerulus, either via deposition of immune complexes, auto-immune phenomena, or through cytopathogenic effects. This chapter describes the epidemiology of hepatitis A-, B-, C-, and E-associated GN; the clinical and biological presentations; the histological patterns; and management regimens. Few cases of hepatitis A- or hepatitis E-associated GN have been reported. Cryoglobulinemic membranoproliferative glomerulonephritis is the most common type of GN diagnosed in patients infected by the hepatitis C virus. Patients infected by hepatitis B mainly develop membranous nephritis. Viral clearance using antiviral therapies, when available, is necessary to improve kidney outcomes.

Obstructive Uropathies

Obstructive Uropathy remains an important cause of acute kidney injury. The etiology of obstructive uropathy can be very variable ranging from extrinsic compression of the urinary tract by tumors or surrounding structures to intraluminal obstruction by crystals and stones. Patients with obstructive uropathy manifest symptoms based on the area of obstruction within the urinary tract. Flank pain, hematuria, and suprapubic discomfort are some of the associated symptoms. The diagnosis of obstructive uropathy requires a high index of suspicion and, depending on its nature, can be confirmed clinically and/or with an imaging modality. Prompt diagnosis and treatment with effective relief of obstruction is important in preventing long-term and permanent damage to the kidneys.

Renal Protection in Critically Ill Patients

Acute kidney injury complicates over 50% of critical care admissions and is associated with both increased short and long-term mortality and the development or acceleration of chronic kidney disease. While in certain settings, such as cardiac surgery, primary prevention of AKI is possible, in most cases AKI is present or evolving at intensive care unit admission and the main clinical focus is secondary prevention of further kidney injury. In the absence of evidence for specific AKI-targeted therapies, high quality supportive care to maximize hemodynamic stability and avoidance of secondary sources of kidney injury are the cornerstones of renal protection. Fluid overload is particularly associated with adverse outcomes in critical illness complicated by AKI. Continuous methods of renal replacement therapy may promote hemodynamic stability and have been associated with better longer term renal outcomes.

Renal Artery Stenosis and Revascularization

Stenosis of the renal arteries is a relatively common finding in patients with kidney function impairment, often in the setting of generalized atherosclerotic disease. Most cases of renal artery stenosis are atherosclerotic and found in smokers or elderly patients. Fibromuscular dysplasia is less common and occurs more in younger patients and in the distal segments of the renal artery. Although reasonably easy to find, it is challenging to know what to do when atherosclerotic renal disease is present. Correction of obstructing lesions has high technical success, with relatively low risk, but the controlled trial data comparing intervention with medical therapy in atherosclerotic renovascular disease shows similar outcomes on blood pressure and kidney function. Younger people with fibromuscular dysplasias, on the other hand, appear to benefit from intervention. Limitations in the field and areas of opportunity include determining what characterizes a clinically significant obstructive lesion and in which circumstances has ischemic disease rendered intervention inconsequential.

Risk Factors for Chronic Kidney Disease

Chronic kidney disease (CKD) represents a significant public health burden worldwide and several risk factors have been identified over the years; these have been well-described in the medical literature. Common risk factors such as diabetes mellitus and hypertension will be described in other chapters. While this chapter will focus mainly on CKD risk factors observed in developed countries, several of these are also observed in developing countries. It is now well-established that some risk factors are modifiable while others are non-modifiable. In this chapter, we will explore several of these non-modifiable risk factors in more detail, such as age, gender, race, family history, and low birth weight. But we will also discuss some of the modifiable risk factors such as kidney stones, obstructive sleep apnea, smoking, drugs (excluding NSAIDs), diet, obesity, metabolic syndrome, and hyperuricemia. We will provide a balanced and up to date review of the evidence linking these risk factors with CKD.

Adaptation in Acute Kidney Injury

It is well established that patients who develop acute kidney injury (AKI) are at increased risk for progression to chronic kidney disease (CKD). However, by the time AKI is clinically recognized, a sequence of events with potential to repair the injury or propagate further damage to the renal parenchyma is already initiated. The outcome of the repair process depends on adaptive and maladaptive influences at the cellular level. Progression to CKD after AKI is the result of imbalance in favor of maladaptive repair, which culminates in the development of interstitial fibrosis. Various biochemical pathways are implicated in this process and may lend themselves to potential therapeutic targets for intervention in the transition from AKI to CKD. Emerging methods, including injury-specific biomarkers for the earlier detection of subclinical disease, show promise for use in combination with clinical factors and functional markers to stratify patient risk for CKD progression after AKI.

Pathogenesis of Acute Kidney Injury

Acute kidney injury represents a significant clinical disorder associated with a rapid loss of renal function following a variety of potential insults. This chapter reviews multiple issues related to the pathophysiology of AKI with an emphasis on studies from animal models. Early responses following kidney injury include impaired hemodynamic and bioenergetic responses. Reductions in renal ATP levels occur as a result of compromised fatty acid oxidation and impaired compensation by glycolysis. Sustained reductions in perfusion contribute to extension of AKI characterized by complex inflammatory and cellular injury responses, often leading to cell death. Concurrently, the kidney displays an elegant repair response, leading to successful recovery in most cases, characterized in part by epithelial cell growth, while maladaptive or incomplete recovery of tubules or capillaries can predispose the development of interstitial fibrosis and CKD progression.

Cardiac Surgery and the Kidney

Kidney injury is a frequent and serious complication following cardiac surgery with significant short-term and long-term morbidity. Cardiopulmonary bypass (CPB), utilized during cardiac surgery, is known to contribute to the development of kidney injury, and the perioperative period provides a unique opportunity for testing renoprotective interventions due to the known timing and similarity of the renal insult. In this chapter preoperative risk factors, surgical, anesthetic, and CPB-related factors that may impact on kidney injury are discussed, with a focus on preoperative and perioperative protective therapies. Therapies discussed include preoperative and perioperative administration of pharmacological agents and intraoperative interventions to reduce the risk of kidney injury post cardiac surgery. Unfortunately, there is a paucity of interventions that definitely protect the kidney from injury during cardiac surgery.

Cystic Kidney Diseases

Autosomal dominant polycystic kidney disease (ADPKD), the most common monogenic kidney disease, is characterized by relentless development of kidney cysts, hypertension, and eventually end-stage renal disease. The enlargement of the bilateral kidney cysts is gradual throughout the lifetime of the patient until little renal parenchyma is recognizable. At that stage, the average rate of GFR decline is 4.4 to 5.9 mL/min/year. Over the past few years, several advancements in diagnosing, prognosticating, and understanding the pathogenesis of the disease have been made. The natural course of ADPKD makes it an ideal disease to be targeted for renal protection. This chapter discusses various aspects of pathophysiology and molecular pathways and addresses in details the various pharmaceutical and nonpharmaceutical interventions in the journey of prevention of clinical complications of ADPKD.