Chronic Kidney Disease Past Paper PDF

ESGUERRA, MPSTAZA, NAVARRO, RAMOS,REYES, ROBLES, SAPPAYANI, SUBIJANO | EBPT 1 1  CHRONIC KIDNEY DISEASE...

ESGUERRA, MPSTAZA, NAVARRO, RAMOS,REYES, ROBLES, SAPPAYANI, SUBIJANO | EBPT 1 1  CHRONIC KIDNEY DISEASE This leads to hyperfiltration, where the remaining nephrons compensate for the loss by filtering more for each nephron. There will be an increased single nephron glomerular filtration rate which means that each surviving/remaining PATHOPHYSIOLOGY nephron filters a larger volume of plasma that it is supposed to.  CKD presents as a progressive loss of renal function  There is also glomerulosclerosis. Over time, the increased pressure and o Progressive reduction in the Glomerular Filtration Rate hyperfiltration damage the remaining functional nephrons, leading to glomerulosclerosis or the scarring and loss of glomeruli. for three or more months  The damage leads to a vicious cycle. As more nephrons are lost, the remaining o Increase in proteinuria, specifically albuminuria ones work even harder, further increasing their susceptibility to injury and  This is the strongest predictor of prognosis in CKD continuing the progression of kidney damage. due to cardiovascular risk  Indicative of chronic injury to the kidney GLOMERULOSCLEROSIS  Generally, there are 1.2 million nephrons in each kidney.  Leads to progressive loss of nephrons causing reduction in renal function  Manifested as fibrous tissue and inflammation in the glomerulus and bowman’s capsule due to mesangial cells secreting extracellular matrix thickening the glomerular basement membrane altering the filtration process. Waste products such as urea, creatinine, water, and potassium filtration are hindered and accumulate in the body  Complications include: ISCHEMIC/HYPERTENSIVE RENAL DISEASE o Increase in BUN → uremia  Ischemic nephropathy was traditionally referred to as o Increase in creatinine under perfusion of the kidneys caused by renal artery o Increase in potassium levels → hyperkalemia stenosis. o Increase in protons → acidosis o Renal artery stenosis pertains to narrowing of the main arteries o Increase in sodium and water → hypervolemia supplying the kidney.  Inflammation also alters the permeability of the filtration  Hypertension results in atherosclerosis (fat build up) and membrane arteriosclerosis (hardening of arteries), which can cause o Increase in permeability causes proteins especially occlusive renovascular disease and small-vessel damage. albumin to leak out leading to albuminuria o This reduced blood flow impairs kidney function and can progress to chronic kidney disease (CKD). o Albuminuria leads to complications such as:  These diagnoses account for around 30% of CKD.  Increased risk of cardiovascular disease from the increased synthesis of lipoproteins in the liver, METABOLIC DISEASES increasing the risk of atherosclerosis and other  Diabetes mellitus is the most common metabolic disease cardiovascular events that causes CKD. The predominant lesion is glomerular and ETIOLOGY is referred to as diabetic nephropathy or diabetic kidney disease.  The mechanism of damage depends on the underlying cause o Diabetes mellitus is the leading cause of CKD and is associated with a of renal disease. kidney condition called diabetic nephropathy or diabetic kidney disease.  Individual nephrons become damaged and fail, remaining  Patients with diabetes usually have proteinuria; high levels nephrons compensate for loss of function through of proteinuria are associated with an increased risk of hyperfiltration secondary to raised intra-glomerular progression of CKD. pressure. o The main problem occurs in the glomeruli (filtering units of the kidney), o The functional unit of the kidney is the nephron; there are 1 million where damage leads to proteinuria (protein in the urine). nephrons in each kidney. Nephrons are responsible for filtering blood, o High levels of proteinuria indicate more severe kidney damage and an removing waste, and regulating the body's fluid, electrolyte, and acid- increased risk of CKD progressing to end-stage renal disease (ESRD), base balance. requiring dialysis or a kidney transplant. o The patient remains well until so many nephrons are lost that the GFR  Diabetes is present in up to one-third of patients with CKD. can no longer be maintained despite activation of compensatory mechanisms. As a consequence, there is a progressive decline in kidney CHRONIC GLOMERULONEPHRITIS function.  Glomerulonephritis is a term that is used to describe the MECHANISM OF PROGRESSIVE RENAL DAMAGE process of inflammation of the glomerulus. This flowchart explains the mechanism of progressive renal damage and how it o Glomeruli are tiny filtering units in the kidneys leads to worsening kidney function. Here's a breakdown of the process:  The most common cause of chronic glomerulonephritis is IgA  The reduction in renal function observed in CKD is often a patchy process, nephropathy; this is characterized by deposition of resulting from damage to the structure of the kidney in discrete areas rather than throughout the kidney. A primary kidney disease such as diabetes, polymeric IgA in the glomerulus with subsequent immune hypertension, or glomerulonephritis initiates damage in the kidney. activation.  This will lead to nephron damage and loss. The disease causes damage to  Chronic glomerulonephritis causes around 15% of cases of functional units of the kidney, which are the nephrons. As a result, some nephrons are lost or impaired. advanced CKD.  Next, as individual nephrons become damaged and fail, remaining nephrons LOWER URINARY TRACT DISEASE compensate for loss of function. 'Bystander' injury refers to the secondary nephron loss, wherein the remaining nephrons take on an increased workload,  Represent 5-10% of all cases of CKD. leading to increased glomerular capillary pressure. This is the result of more o A variety of differing pathologies make up this group, which include blood being filtered by fewer nephrons, which causes strain. the following conditions: reflux disease, renal stone disease, chronic pyelonephritis and extrinsic renal tract obstruction.  ESGUERRA, MPSTAZA, NAVARRO, RAMOS,REYES, ROBLES, SAPPAYANI, SUBIJANO | EBPT 1 2 REFLUX DISEASE POLYURIA AND NOCTURIA  Results from reflux of urine back up the renal tract towards POLYURIA the kidneys. o This can result in recurrent infections and subsequent scarring.  The patient frequently voids high volumes of urine, is often seen in CKD and results from medullary damage and RENAL STONE DISEASE insensitivity to ADH. In people with advanced CKD it can  Kidney stones are primarily formed of calcium oxalate and also be related to the osmotic effect of a high serum urea calcium phosphate. level (>40 mmol/L), which pulls more water into the urine. o They can cause urinary tract obstruction and infection. NOCTURIA CHRONIC PYELONEPHRITIS  The patient will wake overnight needing to pass urine.  Recurrent urinary tract infections which ascend to involve the o Patient wakes up at night to urinate, often because the kidneys are less able to concentrate urine, leading to increased nighttime urine kidneys can cause renal scarring. production. o This is often associated with reflux disease but may occur without it. EXTRINSIC RENAL OBSTRUCTION PROTEINURA AND ALBUMINURIA  Most common in males with prostatic hypertrophy. PROTEINURIA  When protein levels in the urine climb above a threshold HEREDITARY/CONGENITAL DISEASES level.  5% of CKD cases are hereditary. o The common inherited conditions are APKD and Alport’s syndrome. ALBUMINURIA AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE  Around 70% of all proteinuria is albuminuria, and it is (APKD) albuminuria that is used to contribute to the classification of  An inherited condition which results in the formation of CKD. o Albuminuria is measured by using single urine samples to determine the multiple cysts in both kidneys through-out life. ACR or (in some laboratories) the protein/creatinine ratio. o The kidneys become enlarged and frequently fail in middle age. Albuminuria ACR (mg/mmol) Description ALPORT’S SYNDROME stage (by ACR) (urine dip test)  A disorder of glomerular basement membranes caused by A1 30 Very high  The table categorizes albuminuria stages based on the albumin-to-creatinine UNKNOWN CAUSE ratio (ACR), a marker of kidney damage.  Unknown in around 30% of CKD patients. o A1 (ACR 30 mg/mmol) indicates very high albumin levels, suggesting possible to carry out a renal biopsy to determine the significant kidney damage and a higher risk of chronic kidney disease underlying cause. (CKD) progression. o Without a clear immunological profile or identifiable pathology, o Higher stages (A2 and A3) require medical attention to prevent further clinicians may struggle to pinpoint the exact etiology of the CKD, kidney function decline. making management and treatment more difficult. HEMATURIA CLINICAL MANIFESTATIONS  The presence of blood in the urine can be caused by either  Symptoms of advanced kidney disease are known as uremic renal or lower urinary tract pathology. symptoms. o Hematuria can be either invisible (microscopic) or visible (gross). The best way to test for hematuria is with a urinary dip test. o Although uremic symptoms are rare in stage G4 CKD, they become more apparent as the patient enters  Blood and/or protein in the urine is described as an active stage G5 CKD and approaches ESRD. urinary sediment. o Whenever blood in the urine is detected, an infection should be considered and excluded by quantification of white cells and culture for organisms. HYPERTENSION AND FLUID OVERLOAD HYPERTENSION  Leads to sodium retention, which in turn produces circulatory volume expansion with consequent hypertension. o Volume-dependent hypertension occurs in about 80% of patients with CKD, and this is more prevalent with more advanced CKD. This form of hypertension is often termed ‘salt-sensitive’ because it may be exacerbated by salt intake. o As the eGFR falls to very low levels the kidneys are unable to excrete salt and water adequately, resulting in the retention of extravascular Clinical manifestations of CKD may affect the central nervous system, renal, fluid. hormonal, bone, blood, cardiovascular system, gastrointestinal tract, and may include peripheral neuropathy.  ESGUERRA, MPSTAZA, NAVARRO, RAMOS,REYES, ROBLES, SAPPAYANI, SUBIJANO | EBPT 1 3 FLUID OVERLOAD OSTEOMALACIA (REDUCED MINERALIZATION)  Manifest as peripheral and pulmonary edema and ascites.  Impaired 1α-hydroxylation leads to active vitamin D  Edema may be seen around the eyes on waking, the sacral deficiency, reducing calcium absorption and causing region in supine patients and from the feet upwards in osteomalacia. ambulatory patients. MIXED RENAL OSTEODYSTROPHY UREMIA  Combination of both hyperparathyroidism and  Small molecules including urea, creatinine and water are osteomalacia. normally excreted by the kidney and accumulate as renal ADYNAMIC BONE DISEASE function decreases.  Reduced bone formation and resorption. o There are a wide range of uremic toxins, but it is the blood level of o Reflecting a state of low metabolic activity in the bones. urea that is still used to estimate the degree of toxin accumulation in CKD.  Symptoms include: RENAL & HEPATIC INVOLVEMENT IN VIT. D METABOLISM o anorexia, nausea, vomiting, constipation, foul taste and skin discoloration that is presumed to be due to pigment deposition compounded by the pallor of anemia. o In severe cases crystalline urea is deposited on the skin (uremic frost).  In uremia, there is also an increased tendency to bleed, which can exacerbate pre-existing anemia because of impaired platelet adhesion including modified interactions between platelets and blood vessels resulting from altered blood rheology. ANEMIA  Affects most people with stages G4 and G5 CKD. o The decrease in hemoglobin level is a slow, insidious process accompanying the decline in renal function.  The principal cause results from damage of peritubular cells leading to inadequate secretion of erythropoietin. This diagram illustrates the role of the liver and kidneys in the metabolism of vitamin o This hormone, which is produced mainly in the kidney, is D. Vitamin D plays a central role in calcium and phosphate balance, which are critical for bone formation and remodeling. the main regulator of red cell proliferation and  The process of vitamin D metabolism involves the liver and kidneys working differentiation in bone marrow. together to activate vitamin D. It begins with cholecalciferol (vitamin D3),  Anemia in CKD is a major cause of fatigue, breathlessness obtained from diet or sunlight, which is inactive. at rest and on exertion, and lethargy.  In the liver, it is converted into 25-hydroxycholecalciferol, another inactive o Patients may also complain of feeling cold, poor concentration and form but serves as the main storage and transport form of vitamin D in the reduced appetite and libido. body. This compound is transported to the kidneys, where it undergoes further o Several factors contribute to the pathogenesis of anemia in CKD, conversion by the enzyme 1α-hydroxylase, producing 1,25- including shortened red cell survival, marrow suppression by uremic dihydroxycholecalciferol (calcitriol), the active form of vitamin D. toxins and iron or folate deficiency associated with poor dietary intake o Calcitriol promotes calcium absorption in the intestines, regulates or increased loss, for example, from gastrointestinal bleeding. calcium levels in the blood, and supports bone mineralization.  Additionally, the intermediate form 1α-hydroxycholecalciferol (alfacalcidol) BONE DISEASE (RENAL OSTEODYSTROPHY) can also be used therapeutically to bypass kidney conversion in patients with  Bone pain is the main symptom, and distinctive appearances kidney disease. on radiographs may be observed, such as the ‘rugger- DISTURBANCE OF CALCIUM AND PHOSPHATE BALANCE jersey’ spine, where there are alternate bands of excessive and defective mineralization in the vertebrae. o Shown in the photo is a lateral radiograph of the spine in a patient with chronic renal failure. Characteristic endplate sclerosis shown with the arrows is referred to as “rugger-jersey spine”. o The areas pointed by the arrows are dense bands that appear radiopaque or white on X-rays. In contrast, the less dense areas signify regions of reduced mineralization or osteomalacia, these are located in the central portions of the vertebrae which appear radiolucent or darker on the X-ray. This pattern is commonly associated with renal osteodystrophy in patients with chronic kidney disease.  Renal osteodystrophy encompasses four distinct bone disorders linked to chronic kidney disease (CKD), each resulting from the complex interplay of mineral and hormonal imbalances. SECONDARY HYPERPARATHYROIDISM  Produces a disturbance in the normal architecture of bone, and this is termed osteosclerosis. o Secondary hyperparathyroidism occurs due to elevated parathyroid hormone levels, leading to osteosclerosis, which is characterized by abnormal hardening of the bone. This diagram illustrates the disruption of calcium and phosphate balance in chronic renal failure.  Renal failure reduces the kidney's ability to produce 1,25- dihydroxycholecalciferol (active vitamin D), leading to decreased calcium absorption from the gastrointestinal (GI) tract and reduced bone  ESGUERRA, MPSTAZA, NAVARRO, RAMOS,REYES, ROBLES, SAPPAYANI, SUBIJANO | EBPT 1 4 mineralization. These changes can result in osteomalacia, a condition where bones become soft and weak. RISK FACTORS  Simultaneously, renal failure decreases phosphate excretion, causing a buildup of phosphate in the blood (hyperphosphatemia). High phosphate DOMAIN EXAMPLE CONDITIONS levels lower serum calcium, triggering secondary hyperparathyroidism Common Risk  Hypertension (increased parathyroid hormone production) to restore calcium levels. This Factors compensation can cause excessive bone remodeling and osteosclerosis, where  Diabetes bones become abnormally dense.  Cardiovascular disease (including  The interplay of these processes highlights the complex impact of kidney heart failure) failure on bone and mineral metabolism.  Prior AKI/AKD NEUROLOGICAL CHANGES People who live in  Areas with endemic CKDu  Include poor concentration, memory impairment, irritability geographical  Areas with a high prevalence of and stupor. areas with high APOL1 genetic variants  Fits (seizures) caused by cerebral edema or hypertension prevalence of CKD  Environmental exposures may occur. Genitourinary  Structural urinary tract disease  A ‘glove and stocking’ peripheral neuropathy and/or a disorders  Recurrent kidney calculi mononeuritis multiplex can occur. o Patients may experience peripheral neuropathy, characterized by a Multisystem  Systemic lupus erythematosus "glove and stocking" distribution of sensory loss, where the symptoms disease/chronic  Vasculitis affect the hands and feet, or mononeuritis multiplex, which involves the inflammatory  HIV simultaneous dysfunction of multiple peripheral nerves. conditions MUSCLE FUNCTION Iatrogenic (related  Drug-induced nephrotoxicity and  Muscle cramps and restless legs are common and may be to drug treatments radiation nephritis major symptoms causing distress to patients, particularly at and procedures) night. Family history or  Kidney failure, regardless of the o These cramps may be related to electrolyte imbalances, fluid retention, known genetic identified cause or other metabolic disturbances associated with kidney dysfunction. variant associated  Kidney disease recognized to be  Rarely a proximal myopathy of shoulder and pelvic girdle with CKD associated with genetic muscles may develop. abnormality (e.g., PKD, APOL1- o This further impacts mobility and daily activities. mediated kidney disease, and ELECTROLYTE DISTURBANCES Alport syndrome) Because the kidneys play such a crucial role in the maintenance of volume, Gestational  Preterm birth extracellular fluid composition and acid–base balance, disturbances of electrolyte conditions levels are common in CKD.  Small gestational size  Sodium - either hypernatremia or hyponatremia  Pre-eclampsia/ eclampsia o Patients may have hyponatremia or hypernatremia depending upon the Occupational  Cadmium, lead, and mercury condition and therapies. Hyponatremia often happens when the kidneys exposures that can't get rid of excess water, leading to diluted sodium in the blood, or exposure due to the use of diuretics that promote sodium loss. On the other hand, promote CKD risk  Polycyclic hydrocarbons hypernatremia can occur if patients become dehydrated, either from  Pesticides not drinking enough fluids or from fluid losses due to vomiting or AKD, acute kidney disease; AKI, acute kidney injury; APOL1, apolipoprotein L1; diarrhea, causing sodium levels to rise. CKD, chronic kidney disease; CKDu, chronic kidney disease of undetermined origin;  Potassium - hyperkalemia PKD, polycystic kidney disease. o Potassium levels can be elevated in CKD; this is a potentially catastrophic complication because the first indication of elevated DIAGNOSIS potassium levels may be a cardiac arrest. Serum potassium levels  CKD is usually discovered on a routine blood test greater than 7.0 mmol/L are life-threatening and should be treated as an emergency.  Functional assessment of the kidney may be performed by  Hydrogen ions - H+ is retained, causing acidosis testing serum and urine. o Hydrogen ions (H+) are produced as byproducts of various metabolic o Serum creatinine level - measurement of choice for processes in the body, and under normal circumstances, the kidneys estimating excretory kidney function excrete about 40–80 mmol of H+ daily to help maintain acid-base o Urine - may change in color resulting from blood balance. However, in chronic kidney disease (CKD), the kidneys' ability to filter and eliminate these hydrogen ions is significantly impaired. As staining by whole cells or hemoglobin, drugs, or a result, H+ accumulates in the bloodstream, leading to a condition metabolic breakdown of products. It may also appear known as metabolic acidosis. milky, cloudy from infection, contain crystals and casts, KDIGO (2024) COMMON SYMPTOMS IN CKD or froth from proteinuria  Dipstick tests - simple and rapid estimation of urinary parameters, including: o pH o Specific gravity o Leukocytes o Nitrites o Glucose o Blood o protein  Hyperkalemia, acidosis with correspondingly low serum bicarbonate level, hypocalcemia, and hyperphosphatemia  ESGUERRA, MPSTAZA, NAVARRO, RAMOS,REYES, ROBLES, SAPPAYANI, SUBIJANO | EBPT 1 5 are frequently present and can help differentiate a new CKD from AKI ULTRASONOGRAPHY  Produces two-dimensional images using sound waves and is used as the first-line investigational tool in many hospitals  Harmless, non-invasive, quick, inexpensive, enables measurements to be made and produces images in real time  Useful in the differentiation of renal tumors from cysts and in the assessment of renal tract obstruction COMPUTED TOMOGRAPHY, MAGNETIC RESONANCE IMAGING, AND INTRAVENOUS UROGRAPHY IVU  Rarely used due to it using high doses of radiation and contrast media and providing less information CT AND MRI  Produce very detailed images that include an assessment of the blood supply into the kidney and the drainage of the kidneys. CLASSIFICATION AND STAGING o CT - is the investigation of choice for patients with  To determine the classification and stage of CKD, a renal obstruction of the renal tract by renal imaging function panel must be done o MRI - provide enhanced soft tissue assessment and also o Glomerular filtration rate avoid the use of contrast media that can cause renal o Dipstick test for albumin in the urine damage  The figure below shows the values of GFR and albumin and  CT or MRI can provide the following information: their corresponding interpretation and stages. o Presence, length, and position of kidneys  CKD patients generally have shrunken kidneys due to nephron loss, with polycystic disease being the exception  Presence and absence of renal scarring and shape of the calyces and renal pelvic  Obstruction to the ureters by stone, tumor, or retroperitoneal fibrosis, which may require surgical intervention  Presence of cyst or solid mass in the kidneys  Detailed information on the blood supply into and out of the kidneys NUCLEAR MEDICINE INVESTIGATIONS MERCAPTO ACETYL TRIGLYCERIDE  Used for assessment of renal perfusion and identification of outflow obstruction DIMERCAPTOSUCCINIC ACID SCAN To determine the classification (Albuminuria category) and stage (GFR category),  Ascertain the percentage that each kidney contributes to the we must plot it using the figure above. For example, if a patient has a GFR of 70, overall function they are on stage G2 with an interpretation of Mildly decreased. If their albumin result is 100 mg/g, they are classified as A2, which is moderately increased. Once RENAL BIOPSY the classification and stage are identified, plot where the two of them meet in the figure on the lower right. In this example, G2 and A2 meet at the TREAT 1 spot.  Done when imaging techniques fail to give a cause for the This means that the patient should be pharmacologically treated and re-evaluated reduction in renal function every year. The number below every condition indicates the number of times per  Advanced disease extensive scarring of renal tissue may year the patient should be evaluated for disease progression and assessment of treatment. obscure the original (primary) diagnosis.  In cases of shrunken kidneys, clinicians do not perform biopsies due to patients suffering from subsequent bleeding.  ESGUERRA, MPSTAZA, NAVARRO, RAMOS,REYES, ROBLES, SAPPAYANI, SUBIJANO | EBPT 1 6 PHARMACOTHERAPY MANAGEMENT FOR CKD SIDE EFFECTS HYPERTENSION  Initial GFR reduction (acceptable unless >25%). Key Role: BP control is critical to slow CKD progression.  Hyperkalemia (use loop diuretics or low-potassium diet if levels exceed 5.5 mmol/L). PATHOPHYSIOLOGY:  Dry cough (ACE inhibitors).  Hypertension damages intrarenal vasculature, leading to thickening and hyalinization of arterioles. IMPORTANT NOTES  This reduces renal perfusion, activating the RAAS, causing  Patients with significant early GFR decline (>25%) may vasoconstriction, sodium/water retention, and further require drug cessation and investigation for renal artery worsening hypertension. stenosis. MANAGEMENT  Avoid dual RAAS blockade (ACE inhibitors + ARBs) due to worse outcomes. ACE INHIBITORS/ARBS:  Monitor potassium levels closely; risk of AKI increases with  May cause a temporary eGFR reduction within the first 3 hypotension or infection during acute illness. months.  Renin inhibitors, when combined with ACE inhibitors, are  Continue unless eGFR decline exceeds 25%, as long-term associated with high complication rates and should not be benefits include slowing CKD progression. used.  General Approach: Use similar antihypertensive agents as DIURETICS in other forms of hypertension, with adjustments for renal  Primarily used for salt and fluid overload in CKD, indicated impairment. by edema.  Consideration: Always account for altered drug  Dosage: metabolism due to renal failure. o Loop diuretics: May exceed 250 mg/day of CALCIUM CHANNEL BLOCKER furosemide in advanced CKD.  Preferred agents for CKD patients without proteinuria to o Combine metolazone for synergistic effects or manage hypertension. administer loop diuretics intravenously if oral therapy  Dosage: Varies by agent (e.g., amlodipine, nifedipine). fails. Adjust based on patient needs. MECHANISM OF ACTION MECHANISM OF ACTION  Loop diuretics: Block sodium-potassium-chloride  Reduce calcium influx in vascular smooth muscle cells, reabsorption in the loop of Henle. causing vasodilation.  Thiazides: Ineffective when eGFR