Chronic Kidney Disease| Stages, Causes, Pathophysiology, Clinical Presentation, Diagnosis, Treatment

chronic kidney disease also known as chronic renal failure is a term that includes all degrees of decreased kidney function from damaged at risk through mild moderate or severe kidney injury CKD is a worldwide public health problem which carries a relatively poor prognosis it is more prevalent in elderly population however younger people and children may also experience Progressive chronic kidney disease according to the reports of who kidney disease is the 10th leading cause of death around the world CKD is associated with an increased risk of cardiovascular disease and end-stage renal disease the kidney disease outcomes quality initiative or kedoki of the National Kidney Foundation of United States has established a definition and classification for CKD in 2002. according to this CKD is defined as kidney damage or a decreased GFR of less than 60 milliliters per minute per 1.73 square meters which is the average body surface area of a normal adult for at least three months according to the above mentioned classification the stages of CKD are as follows stage 1 kidney damage with normal or increased GFR typically more than 90 milliliters per minute per 1.73 square meters stage 2 mild reduction in GFR typically between 60 to 89. stage 3A moderate reduction in GFR typically between 45 to 59. stage 3B moderate reduction in GFR typically between 30 to 44. stage 4 severe reduction in GFR typically between 15 to 29. and Stage 5 severe reduction in GFR typically less than 15 milliliters per minute per 1.73 square meters or dialysis however measurement of GFR alone may not be sufficient to identify the stage 1 and 2 of CKD in such cases presence of one or more of the following markers of kidney damage can establish the diagnosis albuminuria of more than 30 milligrams per day or an albumin creatinine ratio of more than 30. urine sediment abnormalities electrolyte and other abnormalities due to tubular disorders histologic abnormalities structural abnormalities detected by Imaging studies and history of kidney transplantation now let's discuss about the causes and pathophysiology of chronic kidney disease a normal kidney contains approximately 1 million nephrons Each of which contributes to the total glomerular filtration rate regardless of the cause the ultimate factor which leads to CKD is kidney injury which causes irreversible loss of functional nephrons most common cause for this kidney injury in CKD is diabetic nephropathy although the exact cause of diabetic nephropathy is unknown three main pathological manifestations are thought to be the cause for the development of diabetic nephropathy including hyperglycemia which causes hyperfiltration followed by renal injury formation and deposition of advanced glycation end products in various parts of the kidneys including glomerular vessels glomerular basement membrane and extracellular Matrix of the Nephron and increased production of cytokines such as interleukin-1 and tumor necrosis Factor Alpha and growth factors such as transforming growth factor beta and Vascular endothelial growth factor these pathologies lead to three main histologic changes in the nephrons thickening of the glomerular basement membrane mesangel expansion and glomerulus sclerosis which may result in irreversible loss of nephrons another main cause of CKD is hypertension persistent hypertension causes thickening of arterial walls in this case the renal arteries and this will lead to less blood supply to the kidneys which in turn will cause activation of renin angiotensin aldosterone system and further increase the blood pressure this will cause more thickening of arterial walls and lead to ischemic necrosis of the nephrons unrecovered acute renal failure is another cause acute renal failure is reversible however if not corrected it can lead to chronic kidney disease there are many causes for acute renal failure find the causes for acute renal failure and make a list as today's homework another cause for CKD is vascular diseases including renal artery stenosis atheroimboli and thromboemboli hypertensive nephrosclerosis vasculitis and renal vein thrombosis glomerular diseases also can cause irreversible nephron loss and lead to chronic kidney disease common glomerular diseases include the following membranous nephropathy all Port syndrome IGA nephropathy minimal change disease focal and segmental glomerulus sclerosis membranoproliferative glomerulonephritis and rapidly Progressive glomerulonephritis in addition cystic kidney disease tibulo interstitial diseases urinary tract obstruction or dysfunction recurrent kidney stone disease and congenital defects of the kidney and bladder can cause irreversible nephron loss and lead to chronic kidney disease almost all above mentioned causes are primary causes for CKD in addition to those there are secondary causes for CKD as well these include systemic lupus erythematosis rheumatoid arthritis mixed connective tissue disorder Scleroderma Hepatitis B and C infection syphilis HIV infection and parasitic infections as mentioned earlier regardless of the underlying etiology the main factor that leads to CKD is irreversible nephron loss however despite Progressive destruction of nephrons the kidney has an innate ability to maintain GFR through compensatory hypertrophy of the remaining healthy nephrons and glomerular hyperfiltration this nephron adaptability allows for continued normal clearance of plasma solutes therefore plasma levels of substances such as urea and creatinine start to show measurable increases only after the total GFR has decreased from about 50 of the normal value the hyperfiltration and hypertrophy of residual nephrons although beneficial for the reasons noted has been hypothesized to represent a major cause of progressive renal dysfunction The increased glomerular capillary pressure may damage the capillaries leading initially to secondary focal and segmental glomerulosclerosis and eventually to Global glomerulus sclerosis which causes gradual decrease in GFR now let's discuss about the clinical manifestations of chronic kidney disease patients with CKD stages 1 to 3 are frequently asymptomatic these people do not experience clinically evident disturbances in water and electrolyte balance or metabolic or endocrine functions generally these disturbances become clinically evident in stage 4 and 5 of CKD however patients with tibulo interstitial diseases cystic diseases and nephrotic syndrome may experience symptoms like polyurea hematuria and edema during the early stages of CKD one of the major clinical consequence of CKD is sodium and water handling abnormalities this generally becomes clinically manifested when the GFR Falls less than 10 to 15 milliliters per minute per 1.73 square meters failure of sodium and water excretion leads to sodium and water retention followed by extracellular fluid volume expansion and total body volume overload as kidney function declines further sodium retention and extracellular fluid volume expansion leads to peripheral edema pulmonary edema and hypertension tibulo interstitial renal diseases represent the minority of cases of CKD however it is important to note that such diseases often cause fluid loss rather than overload thus despite moderate or severe reductions in GFR tibulo interstitial renal diseases May manifest first as polyurea and volume depletion with inability to concentrate the urine another manifestation of CKD is hyperkalemia the ability to maintain potassium excretion at near normal levels is generally maintained in CKD as long as aldosterone secretion and distal flow are maintained hyperkalemia usually does not develop until the GFR Falls to less than 20 to 25 milliliters per minute per 1.73 square meters if you can remember your physiology knowledge aldosterone is a hormone that increases the excretion of potassium ions in urine in exchange for sodium it primarily acts on the principal cells of the collecting tubules to increase the uptake of sodium into the blood in exchange for potassium through sodium potassium pumps as you can see in this picture this makes a concentration gradient for sodium from the tubular Lumen all the way to the blood in peritubular capillaries potassium ions which are being pushed into the principal cells are excreted via urine how aldosterone does all these that it activates specific genes in the nucleus and causes expression of sodium potassium pumps sodium channels in the luminal membrane and enzymes required to increase the sodium uptake however during the late stages of CKD aldosterone secretion is reduced due to the reduced renin secretion by the kidneys this causes retention of potassium in the extracellular fluid hyperkalemia can be observed even in the earlier stages of CKD especially in people who ingest a potassium-rich diet or patients who have low serum aldosterone levels due to other reasons such as diabetes mellitus use of ACE inhibitors non-steroidal anti-inflammatory drugs beta blockers and potassium-sparing diuretics whatever the reason hyperkalemia can lead to extremely severe clinical consequences including muscle weakness cardiac arrhythmias and cardiac arrest difficulty in breathing neuropathies nausea and vomiting and diarrhea metabolic acidosis is another major clinical manifestation it results from increased anion gap in CKD proximal tubules of healthy nephrons secrete ammonia to excrete endogenous acids in the form of ammonium but as CKD progresses proximal tubules lack their ability to secrete ammonia which results in reduced acid excretion when the acid secretion is reduced excretion of the anions of these acids is also reduced which results in accumulation of phosphates sulfates and other organic anions in the extracellular fluid this is the reason for increased anion gap and metabolic acidosis in CKD metabolic acidosis has been shown to have deleterious effects on protein balance leading to negative nitrogen balance increased protein degradation increased essential amino acid oxidation reduced albumin synthesis and lack of adaptation to a low protein diet hence metabolic acidosis is associated with protein energy malnutrition loss of lean body mass and muscle weakness in addition metabolic acidosis is a factor for the development of renal osteodystrophy because bone acts as a buffer for excess acid with resultant loss of mineral content in bone metabolic acidosis have been shown to interfere with vitamin D metabolism and patients who are persistently acidotic are more likely to have osteomalacia and low turnover bone disease anemia is another clinical manifestation patients with CKD develop normochromic normocytic anemia due to the reduced synthesis of renal erythropoietin the hormone responsible for bone marrow stimulation for red blood cell production anemia starts early in the course of disease and becomes more severe as viable renal Mass shrinks and GFR progressively decreases no reticulocyte response occurs and the lifespan of red blood cells is decreased bleeding tendency is increased due to uremia-induced platelet dysfunction in addition to lack of erythropoietin secretion there are other causes for anemia in CKD including chronic blood loss as a result of uremia-induced platelet dysfunction Ary hyperparathyroidism which is another main manifestation in CKD patients inflammation nutritional deficiency and accumulation of Inhibitors of erythropoiesis renal bone diseases is also a common clinical finding in CKD patients hyperparathyroidism is the major cause for renal bone diseases common skeletal complications include High turnover bone disease low turnover bone disease defective bone mineralization and beta 2 microgobilin Associated bone disease in addition there are extraskeletal bone diseases as well such as vascular and soft tissue calcification in children renal bone diseases occur during growth therefore children with CKD are at risk for short stature bone curvature and poor mineralization hyperphosphatemia and hypocalcemia is also another complication in CKD phosphate retention begins early in CKD when the GFR Falls less phosphate is excreted in urine but as pth secretion is high in CKD renal excretion of phosphate is maintained in the early stages therefore hyperphosphatemia typically develops in the stage 4 and 5 of CKD hyperphosphatemia suppresses the renal hydroxylation of 25-hydroxovitamin D into calcitriol so the serum calcitriol levels will be low in the late stages of CKD hypocalcemia develops primarily from decreased intestinal absorption of calcium due to low circulating calcitriol levels and increased calcium phosphate binding due to high levels of phosphate in blood as mentioned earlier increased pth levels is another manifestation of CKD low serum calcitriol levels hypocalcemia and hyperphosphatemia have all been demonstrated to independently trigger pth secretion as these stimuli persist in CKD pth secretion becomes maladaptive with time and parathyroid glands become hypertrophic and hyperplastic persistent hyperparathyroidism will exacerbate hyperphosphatemia due to increased bone resorption uremia typically develops later in CKD characteristic features of uremia include the following nausea and vomiting fatigue anorexia weight loss pruritis muscle cramps increased thirst and visual disturbances with mental confusion okay now let's discuss about the diagnosis of CKD it is typically detected by measuring serum creatinine levels to calculate the estimated GFR and by measuring the urinary album in creatinine ratio to detect proteinuria GFR is the best measure to assess kidney function normal GFR varies by age sex and body size of the individual and it is around 120 T 130 milliliters per minute per 1.73 square meters in young adults normal GFR decreases by an average one milliliter per minute per 1.73 square meters in every year after 30 years of age creatinine clearance is used to estimate the GFR and it should be calculated using an equation because creatinine clearance slightly exceeds the actual GFR three equations are used the cockcroft golf equation modification of diet in renal disease equation and chronic kidney disease epidemiology collaboration formula the cockcroft gold equation systematically overestimates GFR an mdrd equation underestimates GFR when it is greater than 60 and it may misidentify persons with normal kidney functions as having CKD ckdepi formula is considered to be the most accurate one proteinuria refers to the increased excretion of protein in urine it is detected by measuring urine albumin creatinine ratio now if albumin amount is calculated in milligrams creatinine amount should be calculated in grams albumin creatinine ratio of less than 30 is considered normal if it is between 30 to 300 that is called microalbuminuria and if it is more than 300 that is called macroalbuminuria in addition to the estimation of GFR and detection of protonuria other tests that can give evidence of CKD include complete blood count basic metabolic panel which will show elevated blood urea nitrogen and serum creatinine levels hyperkalemia and low bicarbonate levels serum phosphate 25-hydroxy vitamin D alkaline phosphatase and pth levels to look for evidence of renal bone disease Imaging studies include renal ultrasonography to detect structural abnormalities such as polycystic kidneys for screening of hydronephrosis and to assess the involvement of retroperitoneum with fibrosis or tumor CT scanning can better Define renal masses and cysts usually noted on ultrasonography and it is the most sensitive test for identifying renal stones renal biopsy is rarely indicated in CKD usually when the diagnosis of underlying etiology is extremely difficult by other methods finally let's discuss about the management of CKD patients with CKD generally experience Progressive loss of kidney function and are at risk of end-stage renal disease the rate of progression depends on age the underlying etiology and the success of secondary preventive measures early diagnosis and treatment of the underlying cause and institution of secondary preventive measures are crucial in patients with CKD early referral to a nephrologist is of extreme importance medical care of a CKD patient should focus on the following delaying or halting the progression of CKD diagnosing and treating the pathologic manifestations of CKD And Timely planning for long-term renal replacement therapy measurements indicated to delay or possibly halt the progression of CKD include the following treatment of the underlying etiology if possible aggressive blood pressure control treatment for hyperlipidemia aggressive glycemic control avoidance of nephrotoxic substances including IV radio contrast media NSAIDs and aminoglycosides use of renin angiotensin system blockers in patients with diabetic kidney disease and use of ACE inhibitors or Angiotensin receptor blockers in patients with protonuria treatment of pathologic manifestations of CKD include treatment of anemia typically when the hemoglobin level is below 10 grams per deciliter with erythropoiesis stimulating agents like epoetin Alpha and darbopoietin Alpha however these drugs should be used with caution in patients with malignancy control of hyperphosphatemia usually by dietary restriction of phosphate and treatment with dietary phosphate binders treatment of hypercalcemia with calcium supplements with or without calcitriol treatment of hyperparathyroidism with calcitriol and vitamin D analogues treatment of volume overload with Loop Diuretics and ultrafiltration treatment of metabolic acidosis with oral alkaline supplementation treatment of uremic manifestations with long-term renal replacement therapy including hemodialysis peritoneal dialysis and renal transplantation dialysis is usually required when the GFR Falls below 15 in Stage 5 CKD and growth failure in children can be treated with growth hormone indications of renal replacement therapy either with dialysis or renal transplantation include the following severe metabolic acidosis hyperkalemia pericarditis encephalopathy uncontrollable volume overload peripheral neuropathy uncontrollable gastrointestinal symptoms and severe uremia unfortunately patients with CKD are advised to take a highly restricted diet protein restriction is indicated for adults who are in Stage 5 CKD to delay the onset of uremic symptoms salt restriction to lower the blood pressure phosphate restriction is usually started early in CKD potassium restriction to control hyperkalemia and taking a diet rich in fruits and vegetables has been shown to delay the progression of CKD