Advances in Chronic Kidney Disease

Chronic kidney disease (CKD) is a major global epidemic associated with increased morbidity and mortality. Despite the effectiveness of kidney protection strategies of hypertension, diabetes, and lipid control and use of newer hypoglycemic agents and anti-angiotensin II drugs, the nephropathy in CKD continues unabated toward irreversible kidney failure. Thus, interventions targeting modifiable risk factors in CKD such as metabolic acidosis (MA) are needed. Acid reduction with sodium-based alkali has been shown to be an effective kidney-protection strategy for patients with CKD and reduced glomerular filtration rate (GFR)...

Metabolic acidosis affects about 15% of patients with chronic kidney disease. As kidney function declines, the kidneys progressively fail to eliminate acid, primarily reflected by a decrease in ammonium and titratable acid excretion. Several studies have shown that the net acid load remains unchanged in patients with reduced kidney function; the ensuing acid accumulation can precede overt metabolic acidosis, and thus, indicators of urinary acid or potential base excretion, such as ammonium and citrate, may serve as early signals of impending metabolic acidosis...

Metabolic acidosis is common in people with chronic kidney disease and can contribute to functional decline, morbidity, and mortality. One avenue through which metabolic acidosis can result in these adverse clinical outcomes is by negatively impacting skeletal muscle; this can occur through several pathways. First, metabolic acidosis promotes protein degradation and impairs protein synthesis, which lead to muscle breakdown. Second, metabolic acidosis hinders mitochondrial function, which decreases oxidative phosphorylation and reduces energy production...

Acid can have ill effect on bone health in the absence of frank clinical acidosis but affecting the bone mioneral matrix and bone cells via complex pathways botyh ascute;y and chronically. While the reaction of bone to an acid load is conserved in evolution and is adaptive, the capacity can be overwhelmed resulting in dire consequences. The preclinical an clincl evidence of the acdi effect on bone is very convincing and the clinical evidence in both association and interventiopn studies are also quite credible, The adverse effects of acid on bone is underappreoicated, under-investigated, and the potential benefits of alkali therapy is not generrally known...

Eating a net acid-producing diet can produce an "acid stress" of severity proportional to the diet net acid load, as indexed by the steady-state renal net acid excretion rate. Depending on how much acid or base is ingested or produced from endogenous metabolic processes and how well our homeostatic mechanisms can buffer or eliminate the additional acids or bases, we can alter our systemic acid-base balance. With increasing age, the kidney's ability to excrete daily net acid loads declines (a condition similar to that of mild CKD), invoking increased utilization of potential base stores (eg, bone, skeletal muscle) on a daily basis to mitigate the acid accumulation, thereby contributing to development of osteoporosis, loss of muscle mass, and age-related renal insufficiency...

Acid accumulation sufficient to reduce plasma bicarbonate concentration, thereby recognized as chronic metabolic acidosis, harms bones and muscles and appears to enhance progression of CKD. Evolving evidence supports that progressive acid accumulation that is not enough to cause chronic metabolic acidosis nevertheless has deleterious effects. Measurable acid retention without reduced plasma bicarbonate concentration, called eubicarbonatemic acidosis, also appears to cause kidney injury and exacerbate CKD progression...

The various mechanisms responsible for the development of metabolic acidosis are briefly reviewed, and the metabolic acidoses are categorized both by mechanism and by the presence or absence of an increased anion gap. When a diagnosis of metabolic acidosis is established, it becomes imperative to identify the primary causative etiology as quickly as possible. This is often readily apparent from the history and physical exam (ie, diabetic ketoacidosis when the glucose is very high in a patient with diabetes mellitus; lactic acidosis in a patient with sepsis and hypotension, etc...

Evaluation of acid-base status depends on accurate measurement of acid-base variables and their appropriate assessment. Currently, 3 approaches are utilized for assessing acid-base variables. The physiological or traditional approach, pioneered by Henderson and Van Slyke in the early 1900s, considers acids as H+ donors and bases as H+ acceptors. The acid-base status is conceived as resulting from the interaction of net H+ balance with body buffers and relies on the H2 CO3 /HCO3 - buffer pair for its assessment...

Normallly the kidneys handle the daily acid load arising from net endogenous acid production from the metabolism of ingested animal protein (acid) and vegetables (base). With chronic kidney disease, reduced acid excretion by the kidneys is primarily due to reduced ammonium excretion such that when acid excertion falls below acid porduction, acid accumulation occurs. With even mild reductions in glomerular filtration rate (60 to 90 ml/min), net acid excretion may fall below net acid production resulting in acid retention which may be initially sequestered in interstitial compartments in the kidneys, bones, and muscles resulting in no fall in measured systemic bicarbonate levels (eubicarbonatemic metabolic acidosis)...

Human kidneys are well adapted to excrete the daily acid load from diet and metabolism in order to maintain homeostasis. In approximately 30% of patients with more advanced stages of CKD, these homeostatic processes are no longer adequate, resulting in metabolic acidosis. Potential deleterious effects of chronic metabolic acidosis in CKD, including muscle wasting, bone demineralization, hyperkalemia, and more rapid progression of CKD, have been well cataloged. Based primarily upon concerns related to nutrition and bone disease, early Kidney Disease Outcomes Quality Initiative guidelines recommended treating metabolic acidosis with alkali therapy targeting a serum bicarbonate ≥22 mEq/L...

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Health care transition (HCT) from pediatric to adult-focused services is a longitudinal process driven by the collaboration and interactions of adolescent/young adult patients, their families, providers, health care agencies, and environment. Health care providers in both pediatric and adult-focused settings must collaborate, as patients' health self-management skills are acquired in the mid-20s, after they have transferred to adult-focused care. Our manuscript discusses the individual and family support systems as they relate to adolescents and young adults with chronic or end-stage kidney disease...

Common causes of pediatric ESRD are distinct from those seen in the adult population. In the pediatric population, the most common are congenital anomalies of the kidney and urinary tract (CAKUT), affecting approximately 30% of children with CKD. These structural anomalies often require coordinated care with the pediatric urology team to address voiding issues, bladder involvement, and the potential need for surgical intervention. For pediatric nephrologists and urologists, common CAKUT that are encountered include antenatal hydronephrosis, obstructive uropathies (eg, posterior urethral valves), and vesicoureteral reflux...

Recent advances in the management of kidney tubular diseases have resulted in a significant cohort of adolescents and young adults transitioning from pediatric- to adult-focused care. Most of the patients under adult-focused care have glomerular diseases, whereas rarer tubular diseases form a considerable proportion of pediatric patients. The purpose of this review is to highlight the clinical signs and symptoms of tubular disorders, as well as their diagnostic workup, including laboratory findings and imaging, during young adulthood...

The pediatric patient with end-stage kidney disease who transitions to the adult dialysis unit or nephrology center requires a unique nutritional focus. Clinicians in the adult center may be faced with complex issues that have often been part of the patient's journey since early childhood. The causes of kidney disease in children are often quite different than those which affect the adult population and may require different nutritional priorities. Abnormal growth including severe short stature, underweight, overweight or obesity, and poor musculature may affect the long-term health and psychosocial well-being of these patients...

Chronic kidney disease is common and causes significant morbidity including shortened lifespans and decrease in quality of life for patients. The major cause of mortality in chronic kidney disease is cardiovascular disease. Cardiovascular disease within the chronic kidney disease population is closely tied with disordered calcium and phosphorus metabolism and driven in part by renal bone disease. The complex nature of renal, bone, and cardiovascular diseases was renamed as mineral and bone disorder of chronic kidney disease to encompass how bone disease drives vascular calcification and contributes to the development of long-term cardiovascular disease, and recent data suggest that managing bone disease well can augment and improve cardiovascular disease status...

Hypertension (HTN) is an important cause of morbidity and mortality in children as well as adults. HTN and related adverse cardiovascular health develop and progress on a continuum across an individual's life course. Pediatric HTN, or even isolated elevated blood pressure as a child, increases the risk of sustained HTN and cardiovascular disease in later adulthood. Transitioning the care of adolescents and young adults who have HTN is an important but unmet health care need that could potentially have a dramatic effect on mitigating the risk of cardiovascular disease in adulthood...

Adolescent obesity and CKD are both significant public health issues independently. When seen as comorbid conditions, they can cause deleterious health outcomes that put them on the fast track to necessitate dialysis or transplantation. This paper analyzes the effects of various biomarkers and comorbidities seen in the intersection of obesity and CKD in the adolescent population. We illustrate the estimated prevalence of these biomarkers and comorbidities through a review of the literature, available treatment, and obesity-related glomerulopathies...

Gaining insight into the complex cycle of renal programming and its early-life clinical associations is essential to understand the origins of kidney disease. Prematurity and intrauterine growth restriction are associated with low nephron endowment. This increases the risk of developing hypertension and chronic kidney disease later in life. There is appreciable evidence to support mechanistic links between low nephron endowment secondary to intrauterine events and kidney size, kidney function, and blood pressure in postnatal life...

Atypical hemolytic uremic syndrome and C3 glomerulopathy/immune complex membranoproliferative glomerulonephritis are ultra-rare chronic, complement-mediated diseases with childhood manifestation in a majority of cases. Transition of clinical care of patients from pediatric to adult nephrologists-typically with controlled disease in native or transplant kidneys in case of atypical hemolytic uremic syndrome and often with chronic progressive disease despite treatment efforts in case of C3 glomerulopathy/immune complex membranoproliferative glomerulonephritis-identifies a challenging juncture in the journey of these patients...