Approach to chronic kidney disease abhijithV Abhijith
Contain almost all major topics associated with chronic kidney disease. Useful for medicine post graduates. I hope this presentation will help you all. Best of luck, thankyou
Approach to chronic kidney disease abhijithV Abhijith
Contain almost all major topics associated with chronic kidney disease. Useful for medicine post graduates. I hope this presentation will help you all. Best of luck, thankyou
chronic kidney disease, diagnosis, management, prognosis, complications, renal replacement therapy, when to initiate hemodialysis, complication of hemodialysis, mortality and morbility.
Acute kidney injury (AKI) is a sudden episode of kidney failure or kidney damage that happens within a few hours or a few days.It's most common in those who are critically ill and already hospitalized.
Acute kidney injury, previously known as acute renal failure, encompasses a wide spectrum of injury to the kidneys, not just kidney failure. The definition of acute kidney injury has changed in recent years, and detection is now mostly based on monitoring creatinine levels, with or without urine output. Acute kidney injury is increasingly being seen in primary care in people without any acute illness, and awareness of the condition needs to be raised among primary care health professionals.
Acute kidney injury is seen in 13–18% of all people admitted to hospital, with older adults being particularly affected. These patients are usually under the care of healthcare professionals practising in specialties other than nephrology, who may not always be familiar with the optimum care of patients with acute kidney injury. The number of inpatients affected by acute kidney injury means that it has a major impact on healthcare resources. The costs to the NHS of acute kidney injury (excluding costs in the community) are estimated to be between £434 million and £620 million per year, which is more than the costs associated with breast cancer, or lung and skin cancer combined.
Brief Information regarding the disorders of the genitourinary system. This presentation involves the disorders of the urinary system including Chronic Kidney Disease, Congenital problems related to the urinary system, and renal cancers.
chronic kidney disease, diagnosis, management, prognosis, complications, renal replacement therapy, when to initiate hemodialysis, complication of hemodialysis, mortality and morbility.
Acute kidney injury (AKI) is a sudden episode of kidney failure or kidney damage that happens within a few hours or a few days.It's most common in those who are critically ill and already hospitalized.
Acute kidney injury, previously known as acute renal failure, encompasses a wide spectrum of injury to the kidneys, not just kidney failure. The definition of acute kidney injury has changed in recent years, and detection is now mostly based on monitoring creatinine levels, with or without urine output. Acute kidney injury is increasingly being seen in primary care in people without any acute illness, and awareness of the condition needs to be raised among primary care health professionals.
Acute kidney injury is seen in 13–18% of all people admitted to hospital, with older adults being particularly affected. These patients are usually under the care of healthcare professionals practising in specialties other than nephrology, who may not always be familiar with the optimum care of patients with acute kidney injury. The number of inpatients affected by acute kidney injury means that it has a major impact on healthcare resources. The costs to the NHS of acute kidney injury (excluding costs in the community) are estimated to be between £434 million and £620 million per year, which is more than the costs associated with breast cancer, or lung and skin cancer combined.
Brief Information regarding the disorders of the genitourinary system. This presentation involves the disorders of the urinary system including Chronic Kidney Disease, Congenital problems related to the urinary system, and renal cancers.
Chronic kidney disease, also called chronic kidney failure, describes the gradual loss of kidney function. Your kidneys filter wastes and excess fluids from your blood, which are then excreted in your urine.
Renal failure and its homeopathy treatment in Chembur, Mumbai, India Shewta shetty
"Treatment & remedies for renal failure and its homeopathy treatment.Personalised online consultancy & treatments provided at our clinic by efficient panel of doctors in our center at mumbai,Bombay,Chembur, India.Contact us."/>
Acute kidney injury (AKI), also known as acute renal failure (ARF), is a sudden episode of kidney failure or kidney damage that happens within a few hours
CKD is a condition in which the kidneys are damaged and cannot filter blood as well as they should. Because of this, excess fluid and waste from blood remain in the body and may cause other health problems, such as heart disease and stroke.
MANAGEMENT OF ATRIOVENTRICULAR CONDUCTION BLOCK.pdfJim Jacob Roy
Cardiac conduction defects can occur due to various causes.
Atrioventricular conduction blocks ( AV blocks ) are classified into 3 types.
This document describes the acute management of AV block.
Ozempic: Preoperative Management of Patients on GLP-1 Receptor Agonists Saeid Safari
Preoperative Management of Patients on GLP-1 Receptor Agonists like Ozempic and Semiglutide
ASA GUIDELINE
NYSORA Guideline
2 Case Reports of Gastric Ultrasound
Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Ve...kevinkariuki227
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
micro teaching on communication m.sc nursing.pdfAnurag Sharma
Microteaching is a unique model of practice teaching. It is a viable instrument for the. desired change in the teaching behavior or the behavior potential which, in specified types of real. classroom situations, tends to facilitate the achievement of specified types of objectives.
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
The prostate is an exocrine gland of the male mammalian reproductive system
It is a walnut-sized gland that forms part of the male reproductive system and is located in front of the rectum and just below the urinary bladder
Function is to store and secrete a clear, slightly alkaline fluid that constitutes 10-30% of the volume of the seminal fluid that along with the spermatozoa, constitutes semen
A healthy human prostate measures (4cm-vertical, by 3cm-horizontal, 2cm ant-post ).
It surrounds the urethra just below the urinary bladder. It has anterior, median, posterior and two lateral lobes
It’s work is regulated by androgens which are responsible for male sex characteristics
Generalised disease of the prostate due to hormonal derangement which leads to non malignant enlargement of the gland (increase in the number of epithelial cells and stromal tissue)to cause compression of the urethra leading to symptoms (LUTS
Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
4. Pathophysiology of CKD
• Mechanisms of Damage
• Initiating mechanisms specific to the underlying etiology
• Set of progressive mechanisms (hyperfiltration and hypertrophy)
5.
6. Risk Factors
• Hypertension
• Diabetes mellitus
• Autoimmune disease
• Older age
• African ancestry
• Family history of renal disease
• Previous episode of acute kidney injury
• Presence of proteinuria
• Abnormal urinary sediment
• Structural abnormalities of the urinary tract
8. Estimation of GFR
• GFR peaks during the 3rd decade of life (120 mL/min per 1.73 m2)
• Annual mean decline in GFR is 1mL/min per year
• At age 70, GFR mean value becomes 70mL/min
• Mean GFR is lower in women than in men
9. Estimation of GFR
• Albuminuria
• 24-hour urine collection – standard
• Spot first morning urine
• Males - >17mg of albumin per gram of creatinine
• Females - >25mg of albumin per gram of creatinine
10. Stages 1 and 2
• Not associated with any symptoms due to a decrease in GFR
11. Stages 3 and 4
• Complications become more prominent
• Anemia – easy fatigability
• Decreasing appetite
• Abnormalities in calcium, phosphorous and mineral regulating
hormones
• Abnormalities in Na, K, water and acid-base homeostasis
14. Leading Categories of Etiologies of CKD
• Diabetic glomerular disease
• Glomerulonephritis
• Hypertensive nephropathy
• Primary glomerulopathy with hypertension
• Vascular and ischemic renal disease
• Autosomal dominant polycystic kidney disease
• Other cystic and tubulointerstitial nephropathy
15. Sodium and Water Homeostasis
• Total-body content of sodium and water is modestly increased
• Dietary intake of sodium > urinary excretion
• Sodium retention and attendant ECFV expansion
16. Potassium Homeostasis
• Hyperkalemia
• Increased dietary potassium intake
• Protein catabolism
• Hemolysis
• Hemorrhage
• Transfusion of stored red blood cells
• Metabolic acidosis
• ACE, ARBS and spironolactone
18. Treatment: Fluid, Electrolyte, and Acid-Base
Disorders
• Adjustments in the dietary intake of salt
• Loop diuretics
• Renal replacement therapy
• Avoidance of K in diet
• Avoidance of K supplements and K-retaining medications
• Kaliuretic diuretics
• Sodium bicarbonate
19. Bone Manifestations of CKD
• The pathophysiology of secondary hyperparathyroidism and the
consequent high-turnover bone disease is related to abnormal
mineral metabolism
• (1) declining GFR leads to phosphate retention
• (2) the retained phosphate stimulates increased synthesis of PTH and growth
of parathyroid gland mass
• (3) decreased levels of ionized calcium also stimulate PTH production.
20. Bone Manifestations of CKD
• Hyperparathyroidism stimulates bone turnover - osteitis fibrosa
cystica
• include bone pain and fragility
• brown tumors
• compression syndromes
• Tumors
• erythropoietin resistance
21. Other Complications of Abnormal Mineral
Metabolism
• Calciphylaxis – heralded by livido reticularis → patches of ischemic
necrosis
24. Treatment: Cardiovascular Abnormalities
• Management of Hypertension
• to slow the progression of the kidney disease itself
• to prevent the extrarenal complications of high blood pressure
• Salt restriction – first line of therapy
• ACE inhibitors
• ARBs
30. Neuromuscular Abnormalities
• Central nervous system (CNS), peripheral, and autonomic neuropathy
• Abnormalities in muscle structure and function
• Early manifestations
• Memory and concentration
• Sleep disturbance
• Late manifestations
• Neuromuscular irritability
• Advanced
• Asterixis
• Myoclonus, seizures
• Coma
35. Evidence of Renal-Bone Disease
• Serum phosphate
• 25-hydroxyvitamin D
• Alkaline phosphatase
• Intact PTH levels
36. Others
• Serum and urine protein electrophoresis
• ANA, anti DS DNA
• Complement levels
• C-ANCA, P-ANCA
• Anti-GBM
• Hepatitis B and C
• HIV
• VDRL
Chronic kidney disease (CKD) encompasses a spectrum of different pathophysiologic processes associated with abnormal kidney function and a progressive decline in glomerular filtration rate (GFR).
A widely accepted classification, based on guidelines of the National Kidney Foundation [Kidney Dialysis Outcomes Quality Initiative (KDOQI)], in which stages of CKD are defined according to the estimated GFR.
The National Kidney Foundation produces clinical practice guidelines through the NKF Kidney Disease Outcomes Quality Initiative (NKF KDOQI)™. This program has provided evidence-based guidelines for all stages of chronic kidney disease (CKD) and related complications since 1997.
The term chronic renal failure applies to the process of continuing significant irreversible reduction in nephron number and typically corresponds to CKD stages 3–5. The dispiriting term end-stage renal disease represents a stage of CKD where the accumulation of toxins, fluid, and electrolytes normally excreted by the kidneys results in the uremic syndrome. This syndrome leads to death unless the toxins are removed by renal replacement therapy, using dialysis or kidney transplantation. End-stage renal disease will be supplanted by the term stage 5 CKD.
The pathophysiology of CKD involves two broad sets of mechanisms of damage: (1) initiating mechanisms specific to the underlying etiology (e.g., genetically determined abnormalities in kidney development or integrity, immune complex deposition and inflammation in certain types of glomerulonephritis, or toxin exposure in certain diseases of the renal tubules and interstitium) and (2) a set of progressive mechanisms, involving hyperfiltration and hypertrophy of the remaining viable nephrons, that are a common consequence following long-term reduction of renal mass, irrespective of underlying etiology.
The responses to reduction in nephron number are mediated by vasoactive hormones, cytokines, and growth factors. Eventually, these short-term adaptations of hypertrophy and hyperfiltration become maladaptive as the increased pressure and flow predisposes to distortion of glomerular architecture, associated with sclerosis and dropout of the remaining nephrons.
Increased intrarenal activity of the renin-angiotensin axis appears to contribute both to the initial adaptive hyperfiltration and to the subsequent maladaptive hypertrophy and sclerosis, the latter, in part, owing to the stimulation of transforming growth factor (TGF-B). This process explains why a reduction in renal mass from an isolated insult may lead to a progressive decline in renal function over many years.
Recent research in the genetics of predisposition to common complex diseases has revealed DNA sequence variants at a number of genetic loci that are associated with common forms of CKD. A striking example is the finding of allelic versions of the APOL1 gene, of West African population ancestry, which contributes to the several-fold higher frequency of certain common etiologies of CKD (e.g., focal segmental glomerulosclerosis) observed among African and Hispanic Americans. The prevalence in West African populations seems to have an evolutionary basis, since these same variants offer protection from tropical pathogens.
In order to stage CKD, it is necessary to estimate the GFR. Two equations commonly used to estimate GFR are shown in and incorporate the measured plasma creatinine concentration, age, sex, and ethnic origin.
The normal annual mean decline in GFR with age from the peak GFR (120 mL/min per 1.73 m2) attained during the third decade of life is 1 mL/min per year per 1.73 m2, reaching a mean value of 70 mL/min per 1.73 m2 at age 70. The mean GFR is lower in women than in men. Thus, even a mild elevation in serum creatinine concentration [e.g., 130 mol/L (1.5 mg/dL)] often signifies a substantial reduction in GFR in most individuals.
Measurement of albuminuria is also helpful for monitoring nephron injury and the response to therapy in many forms of CKD, especially chronic glomerular diseases. While an accurate 24-h urine collection is the criterion standard for measurement of albuminuria, the measurement of protein-to-creatinine ratio in a spot first-morning urine sample is often more practical to obtain and correlates well, but not perfectly, with 24-h urine collections. Persistence in the urine of >17 mg of albumin per gram of creatinine in adult males and 25 mg albumin per gram of creatinine in adult females usually signifies chronic renal damage.
Stages 1 and 2 CKD are usually not associated with any symptoms arising from the decrement in GFR. However, there may be symptoms from the underlying renal disease itself, such as edema in patients with nephrotic syndrome or signs of hypertension secondary to the renal parenchymal disease in patients with polycystic kidney disease, some forms of glomerulonephritis, and many other parenchymal and vascular renal diseases, even with well-preserved GFR.
Stages 3 and 4, clinical and laboratory complications of CKD become more prominent. Virtually all organ systems are affected, but the most evident complications include anemia and associated easy fatigability; decreasing appetite with progressive malnutrition; abnormalities in calcium, phosphorus, and mineral-regulating hormones, such as 1,25(OH)2D3 (calcitriol), parathyroid hormone (PTH), and fibroblast growth factor 23 (FGF-23); and abnormalities in sodium, potassium, water, and acid-base homeostasis. Many patients, especially the elderly, will have eGFR values compatible with stage 2 or 3 CKD. However, the majority of these patients will show no further deterioration of renal function.
Stage 5 CKD, toxins accumulate such that patients usually experience a marked disturbance in their activities of daily living, well-being, nutritional status, and water and electrolyte homeostasis, eventuating in the uremic syndrome. As noted, this state will culminate in death unless renal replacement therapy (dialysis or transplantation) is instituted.
(I) denotes an abnormality that usually improves with an optimal program of dialysis and related therapy
(P) denotes an abnormality that tends to persist or even progress, despite an optimal program
(D) denotes an abnormality that develops only after initiation of dialysis therapy.
This expansion may contribute to hypertension, which itself can accelerate the nephron injury.
Thiazide diuretics plus loop diuretics.
Thiazide – inhibits Na reabsorption in the distal renal tubules resulting in increased excretion of Na and water, also K and H ions
Loop diuretics – inhibits reabsorption of Na and CL ions at the proximal and distal renal tubules and loop of Henle by interfering with chloride-binding cotransport system, causes increases in water, calcium, magnesium, Na and Cl.
In CKD, the decline in GFR is not necessarily accompanied by a parallel decline in urinary potassium excretion, which is predominantly mediated by aldosterone-dependent secretory events in distal nephron segments. Another defense against potassium retention in these patients is augmented potassium excretion in the GI tract.
Hyperkalemia may be precipitated in certain settings. These include increased dietary potassium intake, protein catabolism, hemolysis, hemorrhage, transfusion of stored red blood cells, and metabolic acidosis. In addition, a host of medications can inhibit renal potassium excretion. The most important medications in this respect include the angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), and spironolactone and other potassium-sparing diuretics such as amiloride, eplerenone, and triamterene.
Certain causes of CKD can be associated with earlier and more severe disruption of potassium-secretory mechanisms in the distal nephron, out of proportion to the decline in GFR. These include conditions associated with hyporeninemic hypoaldosteronism, such as diabetes, and renal diseases that preferentially affect the distal nephron, such as obstructive uropathy and sickle cell nephropathy.
The majority of patients can still acidify the urine, but they produce less ammonia and, therefore, cannot excrete the normal quantity of protons in combination with this urinary buffer. Hyperkalemia, if present, further depresses ammonia production. The combination of hyperkalemia and hyperchloremic metabolic acidosis is often present, even at earlier stages of CKD (stages 1–3), in patients with diabetic nephropathy or in those with predominant tubulointerstitial disease or obstructive uropathy; this is a non-anion-gap metabolic acidosis. Treatment of hyperkalemia may increase renal ammonia production, improve renal generation of bicarbonate, and improve the metabolic acidosis.
With worsening renal function, the total urinary net daily acid excretion is usually limited to 30–40 mmol, and the anions of retained organic acids can then lead to an anion-gap metabolic acidosis. Thus, the non-anion-gap metabolic acidosis that can be seen in earlier stages of CKD may be complicated by the addition of an anion-gap metabolic acidosis as CKD progresses. In most patients, the metabolic acidosis is mild; the pH is rarely <7.35 and can usually be corrected with oral sodium bicarbonate supplementation. Animal and human studies have suggested that even modest degrees of metabolic acidosis may be associated with the development of protein catabolism. Alkali supplementation may attenuate the catabolic state and possibly slow CKD progression and accordingly is recommended when the serum bicarbonate concentration falls below 20–23 mmol/L. The concomitant sodium load mandates careful attention to volume status and the potential need for diuretic agents.
Intractable ECFV expansion, despite dietary salt restriction and diuretic therapy, may be an indication to start renal replacement therapy. Hyperkalemia often responds to dietary restriction of potassium, avoidance of potassium supplements (including occult sources, such as dietary salt substitutes) as well as potassium-retaining medications (especially ACE inhibitors or ARBs), or the use of kaliuretic diuretics.
The renal tubular acidosis and subsequent anion-gap metabolic acidosis in progressive CKD will respond to alkali supplementation, typically with sodium bicarbonate.
The pathophysiology of secondary hyperparathyroidism and the consequent high-turnover bone disease is related to abnormal mineral metabolism through the following events: (1) declining GFR leads to reduced excretion of phosphate and, thus, phosphate retention; (2) the retained phosphate stimulates increased synthesis of PTH and growth of parathyroid gland mass; and (3) decreased levels of ionized calcium, resulting from diminished calcitriol production by the failing kidney as well as phosphate retention, also stimulate PTH production. Low calcitriol levels contribute to hyperparathyroidism, both by leading to hypocalcemia and also by a direct effect on PTH gene transcription. These changes start to occur when the GFR falls below 60 mL/min.
Fibroblast growth factor 23 (FGF-23) is part of a family of phosphatonins that promotes renal phosphate excretion.
Hyperparathyroidism stimulates bone turnover and leads to osteitis fibrosa cystica. Bone histology shows abnormal osteoid, bone and bone marrow fibrosis, and in advanced stages, the formation of bone cysts, sometimes with hemorrhagic elements so that they appear brown in color, hence the term brown tumor. Clinical manifestations of severe hyperparathyroidism include bone pain and fragility, brown tumors, compression syndromes, tumors, and erythropoietin resistance in part related to the bone marrow fibrosis.
Calciphylaxis (calcific uremic arteriolopathy) is a devastating condition seen almost exclusively in patients with advanced CKD. It is heralded by livedo reticularis and advances to patches of ischemic necrosis, especially on the legs, thighs, abdomen, and breasts. Pathologically, there is evidence of vascular occlusion in association with extensive vascular and soft tissue calcification.
The optimal management of secondary hyperparathyroidism and osteitis fibrosa is prevention. Once the parathyroid gland mass is very large, it is difficult to control the disease.
Calcitriol exerts a direct suppressive effect on PTH secretion and also indirectly suppresses PTH secretion by raising the concentration of ionized calcium. However, calcitriol therapy may result in hypercalcemia and/or hyperphosphatemia through increased GI absorption of these minerals. Certain analogues of calcitriol are available (e.g., paricalcitol) that suppress PTH secretion with less attendant hypercalcemia.
Cardiovascular disease is the leading cause of morbidity and mortality in patients at every stage of CKD.
Traditional risk factors include hypertension, hypervolemia, dyslipidemia, sympathetic overactivity, and hyperhomocysteinemia.
The CKD-related risk factors comprise anemia, hyperphosphatemia, hyperparathyroidism, sleep apnea, and generalized inflammation. The inflammatory state associated with a reduction in kidney function is reflected in increased circulating acute-phase reactants, such as inflammatory cytokines and C-reactive protein, with a corresponding fall in the "negative acute-phase reactants," such as serum albumin and fetuin. The inflammatory state appears to accelerate vascular occlusive disease, and low levels of fetuin may permit more rapid vascular calcification, especially in the face of hyperphosphatemia. Other abnormalities seen in CKD may augment myocardial ischemia, including left ventricular hypertrophy and microvascular disease. Coronary reserve, defined as the increase in coronary blood flow in response to greater demand, is also attenuated. There is diminished availability of nitric oxide because of increased concentration of asymmetric dimethyl-1-arginine and increased scavenging by reactive oxygen species.
There are two overall goals of therapy for hypertension in these patients: to slow the progression of the kidney disease itself, and to prevent the extrarenal complications of high blood pressure, such as cardiovascular disease and stroke. In all patients with CKD, blood pressure should be controlled to levels recommended by national guideline panels. In CKD patients with diabetes or proteinuria >1 g per 24 h, blood pressure should be reduced to 125/75, if achievable without prohibitive adverse effects.
Salt restriction should be the first line of therapy. When volume management alone is not sufficient, the choice of antihypertensive agent is similar to that in the general population. The ACE inhibitors and ARBs slow the rate of decline of kidney function, but occasionally can precipitate an episode of acute kidney injury, especially when used in patients with ischemic renovascular disease. The use of ACE inhibitors and ARBs may also be complicated by the development of hyperkalemia. Often the concomitant use of a kaliuretic diuretic, such as metolazone, can improve potassium excretion in addition to improving blood pressure control.
Lifestyle changes, including regular exercise, should be advocated but are not often implemented. Hyperlipidemia in patients with CKD should be managed according to national guidelines. If dietary measures are not sufficient, preferred lipid-lowering medications, such as statins, should be used. Again, the use of these agents has not been of proven benefit for patients with advanced CKD.
A normocytic, normochromic anemia is observed as early as stage 3 CKD and is almost universal by stage 4. The primary cause in patients with CKD is insufficient production of erythropoietin (EPO) by the diseased kidneys. Additional factors include iron deficiency, acute and chronic inflammation with impaired iron utilization ("anemia of chronic disease"), severe hyperparathyroidism with consequent bone marrow fibrosis, and shortened red cell survival in the uremic environment. In addition, comorbid conditions such as hemoglobinopathy can worsen the anemia.
Clinical manifestations include fatigue and diminished exercise tolerance, angina, heart failure, decreased cognition and mental acuity, and impaired host defense against infection. In addition, anemia may play a role in growth retardation in children with CKD.
Current practice is to target a hemoglobin concentration of 100–115 g/L.
Clinical manifestations include an increased tendency to bleeding and bruising, prolonged bleeding from surgical incisions, menorrhagia, and spontaneous GI bleeding. Interestingly, CKD patients also have a greater susceptibility to thromboembolism, especially if they have renal disease that includes nephrotic-range proteinuria. The latter condition results in hypoalbuminemia and renal loss of anticoagulant factors, which can lead to a thrombophilic state.
Abnormal bleeding time and coagulopathy in patients with renal failure may be reversed temporarily with desmopressin (DDAVP), cryoprecipitate, IV conjugated estrogens, blood transfusions, and EPO therapy. Optimal dialysis will usually correct a prolonged bleeding time.
Desmopressin – synthetic analogue of vasopressin with prompt onset and longer, more specific antidiuretic action, increases water permeability in renal tubular cells, which in turn decreases urine volume and increases urine osmolality.
Also produces dose-related increase in Von Willebrand factor VIII and t-PA levels, shortens aPTT and BT
Retained nitrogenous metabolites and middle molecules, including PTH, contribute to the pathophysiology of neuromuscular abnormalities.
Subtle clinical manifestations of uremic neuromuscular disease usually become evident at stage 3 CKD. Early manifestations of CNS complications include mild disturbances in memory and concentration and sleep disturbance. Neuromuscular irritability, including hiccups, cramps, and fasciculations or twitching of muscles, becomes evident at later stages. In advanced untreated kidney failure, asterixis, myoclonus, seizures, and coma can be seen.
Uremic fetor, a urine-like odor on the breath, derives from the breakdown of urea to ammonia in saliva and is often associated with an unpleasant metallic taste (dysgeusia). Gastritis, peptic disease, and mucosal ulcerations at any level of the GI tract occur in uremic patients and can lead to abdominal pain, nausea, vomiting, and GI bleeding. These patients are also prone to constipation, which can be worsened by the administration of calcium and iron supplements. The retention of uremic toxins also leads to anorexia, nausea, and vomiting.
Glucose metabolism is impaired in CKD, as evidenced by a slowing of the rate at which blood glucose levels decline after a glucose load. Because the kidney contributes to insulin removal from the circulation, plasma levels of insulin are slightly to moderately elevated in most uremic patients, both in the fasting and postprandial states. Because of this diminished renal degradation of insulin, patients on insulin therapy may need progressive reduction in dose as their renal function worsens. Many hypoglycemic agents require dose reduction in renal failure, and some, such as metformin, are contraindicated when the GFR is less than half of normal.
Pruritus is quite common and one of the most vexing manifestations of the uremic state. In advanced CKD, even on dialysis, patients may become more pigmented, and this is felt to reflect the deposition of retained pigmented metabolites, or urochromes.
A skin condition unique to CKD patients called nephrogenic fibrosing dermopathy consists of progressive subcutaneous induration, especially on the arms and legs. The condition is similar to scleromyxedema and is seen in patients with CKD who have been exposed to the magnetic resonance contrast agent gadolinium.
Complete blood count (CBC)
Basic metabolic panel
Urinalysis (Patients with a P/C ratio above 200 mg/mg should undergo a full diagnostic evaluation. A value of greater than 300-350 mg/mg is within the nephrotic range.)
Serum albumin levels: Patients may have hypoalbuminemia due to urinary protein loss or malnutrition
Lipid profile: Patients with CKD have an increased risk of cardiovascular disease
Evidence of renal bone disease can be derived from the following tests:
Serum phosphate
25-hydroxyvitamin D
Alkaline phosphatase
Intact parathyroid hormone (PTH) levels
Serum and urine protein electrophoresis: Screen for multiple myeloma
Antinuclear antibodies (ANA), double-stranded DNA antibody levels: Screen for SLE
Serum complement levels: Results may be depressed with some glomerulonephritides
Cytoplasmic and perinuclear pattern antineutrophil cytoplasmic antibody (C-ANCA and P-ANCA) levels: Positive findings are helpful in the diagnosis of Wegener granulomatosis and polyarteritis nodosa; P-ANCA is also helpful in the diagnosis of microscopic polyangiitis
Anti–glomerular basement membrane (anti-GBM) antibodies: Presence is highly suggestive of underlying Goodpasture syndrome
Hepatitis B and C, human immunodeficiency virus (HIV), Venereal Disease Research Laboratory (VDRL) serology: Conditions associated with some glomerulonephritides
Renal ultrasonography: Useful to screen for hydronephrosis, which may not be observed in early obstruction, or for involvement of the retroperitoneum with fibrosis, tumor, or diffuse adenopathy; small, echogenic kidneys are observed in advanced renal failure
Retrograde pyelography: Useful in cases with high suspicion for obstruction despite negative renal ultrasonograms, as well as for diagnosing renal stones
Computed tomography (CT) scanning: Useful to better define renal masses and cysts usually noted on ultrasonograms; also the most sensitive test for identifying renal stones
Magnetic resonance imaging (MRI): Useful in patients who require a CT scan but who cannot receive intravenous contrast; reliable in the diagnosis of renal vein thrombosis
Renal radionuclide scanning: Useful to screen for renal artery stenosis when performed with captopril administration; also quantitates the renal contribution to the GFR
Biopsies are also indicated to guide management in already-diagnosed conditions, such as lupus, in which the prognosis is highly dependent on the degree of kidney involvement.
