Chronic Kidney Disease

Chronic kidney disease; consider as one of the major problems in our community, and diabetes mellitus is one of the most common cause of chronic disease. What we mean by chronic kidney -disease? By chronic disease we mean that there is a loss of the function of the kidney. Usually its progressive in nature, leading to advance stage of renal lose, these what we call end stage renal disease in which the person cannot take over, and the kidneys fail to take over and the person is in risk to die.>>> so it's important to know about the function about the kidneys. The function of the kidneys is to maintain the fluid status of the people, The electrolytic, the blood pressure, the hemoglobin, because it has a role in erythropoiesis "and u should know that the kidney is the site where the erythropoietin which is the stimulator cagged for erythropoiesis" 85% of the erythropoietin is producted in the kidney", as well as the calcium and phosphorous hemostasis, this is why is very important to know about the calcium and phosphorous, of course other electrolytes and menials are also have something related to kidney works in the tubules or glomeruli.

PS; Just to know that one in five our patient's>> diabetes will progress in a chronic a disease and amount of 30% of patient's with diabetic they ended in end stage renal disease. -U should know that the diabetes to develop chronic kidney disease needs around not less than ten years, because of multiple mechanism or pathological mechanism. - u should know that the uncontrolled diabetes lead to glaciation of all the membranes including the RBC's leading to thickening of this membranes and loss of the function of this membranes decrease the perfusion of such membranes and the organs as well, this will lead to what we call glomerulosclerosis and chronic disease. In type one diabetes :around 50% of the patients are with diabetes type one which is insulin dependent, its the gubanit type of diabetes. about 45-50% of this patient's develop diabetic nephropathy and chronic disease within 15 to 25 years,, this the natural course of diabetes. -Of course it affect other sites; as the retina, the autonomic nervous system, as well as the vascular system,, but u should know that the diabetes is the most common cause of chronic disease worldwide, and its the most common cause of end stage renal disease.

In type 2 ": its less" is around 20 to 30% its depends on the time of onset of diabetes, if diabetes is started at the age of 30, means that there is time to develop diabetic nephropathy, because we said that its need not less than ten years,

-u should know that if u dont control the blood sugar of ur patients or ur self "if u have diabetes", u have the possibility to develop diabetic nephropathy over 10 to 15 years, and to develop progressive renal disease to advance chronic renal failure because of loss of the function of the nephrons over the next five to ten years leading to end stage renal disease. -by end stage renal disease we mean; that the function of the kidney is totally lost, not more than 7 to 10 percent of the function of the nephron maintain. -Hypertension : patient with diabetes they accelerate there progression into end stage renal disease or chronic kidney disease as they have a hypertension not controlled. Now the hypertension percentage also its the second common cause of the end stage renal disease worldwide, possibly also in our country it's whys very important to control blood pressure. -over 20 to 25 years, the patients might reach the end stage renal disease, within 10 to 15 years ,,,this is very important to know about diabetes and hypertension. Third common cause is chronic perinephritis; by it we mean that we have inflammatory process, immune background, leading to lose of the function of the nephron there is glomerulonephritis, glamorous is affected and sclerosed, leading to lose of the function of the nephron. PS; we know that there is around one million of nephrons and glamorous of course is in each kidney, And u should know that if u have lost of this nephrons this will lead to progressive end stage renal disease.
Diabetes and hypertension both if they coexist this will accelerate the condition of this patient instead of reaching end stage renal disease

The fourth is the chronic Tubulointerstitial nephritis, this is because of obstruction of the urinary tract system, infection, familiar renal diseases with cystic lesions, drugs affecting the tubules or because of others, leading to Tubulointerstitial nephritis, this is in form of pyelonephritis or analgesic nephropathy or reflux nephropathy in children. - if we have a boy or girl with symptoms of urinary tract infection or abdominal pain or dysuria "pain in urination" plz send ur child to do some investigation "urine analysis" if there are RBC's or WBC's in urine, this predict that something wrong with the urinary tract system, because it might be a cause of reflux, defect in the valve between the ureter and the urinary bladder thats what we call vesicoureteral reflux and thats one of the common cause of coronary disease even in adults, but even its the most common cause of end stage renal disease in children, which become aberrant at the time of adulthood. -With age there is a decrease of GFR, and by it we mean the glomerular filtration rate, it's around 110+-20. So(from 90 to 31ml/min),,, this is the actual GFR"CRIATININE CLEARANCE",,, this reflected by lab investigation by serum creatinine level which is between (0.4mg up to 1.2mg) this is the normal values, with age; after the age of 30 or 25 there is a decrease in GFR around (1ml/year) ,,,,, this means that with time as the age of 70 or 80 the normal GFR of that person how is around 80 years is 110 for example minus 16,, its around 50ml/min, "its normal for his age",

this why this patient is compensating if u give him any drug or any toxic agent or the expose for hypotension or u give them something affecting the kidney functions, "nonsteroidal :eg" this will lead to acute renal failure, drop of his GFR, because this toxic for his kidneys, also the self creatinine is normal,, why?? -u will become DR, u will give ur patient nonsteroidal ", diclofenac sodium, ibuprofen" or something else,, U should remember this, u should know what's his age? What his serum creatinine level, because if u give him this drug and he has some degree of renal impairment, or his age above 60-70, this will lead to decrease his GRF and he might cause acute kidney injury, which might not recover leading to end stage renal disease, but even at this time, time of acute kidney injury, or acute renal failure, this is a big problem for these elderly, because the mortality rate is very high, exceeding 50% .

-The finishing as I mention that by chronic disease that there is loss of the function of the kidneys for more than 3 month, at that time u can say that this is a case of chronic disease, before that we cannot say that, if there is loss of function of the kidney we dont know when it started first, if it started acutely ,acute injury, and u know what the cause of that infection "hypertensions, hypotension, bleeding, diarrhea, vomiting, and so on. but if this creatinine clearance persist for more than 3 month, means that the patient has develop chronic kidney disease.

Now there is a stages of chronic kidney disease:

Hypertension* Unable to walk 1/4 mile Serum calcium < 8.5 mg/dL Hemoglobin < 12.0 g/dL Serum albumin < 3.5 g/dL Serum phosphorus > 4.5 mg/dL

Proportion of population (%)

90 80 70 60 50 40 30 20 10 0 15-29 30-59 60-89 90+

Estimated GFR (ml/min/1.73 m 2)

in stage one: creatinine clearance is above 90, but there is a diseased kidney, also the patient has a normally creatinine clearance, normal serum keratin level, we call it chronic disease stage 1. what we mean by diseased kidney??, that the patient for example has glomerulonephritis, or structural defect in the kidney, or he has one kidney, he has experience ,,for example a trauma or something, or stone obstruction,, and he underwent a nephrectomy, has a simple function kidney.

in stage 2: Once creatinine clearance is equation less than 90 ml/min, we call it chronic disease stage 2. when the creatinine clearance is less than 90, reaching to 60, from 89 to 60ml/min. this what we call stage 2 chronic disease.

so: in stage one the GFR is normal, but there is structural defect or functional defects in this kidney

Stage 3: is when the creatinine clearance is less than 60, is 59 up to 30 ml per min, Stage 4: when the creatinine clearance is less than 30, 29 up to 15 ml, Stage5: which is the advance stage, is less than 15 ml ,and in the end stage renal disease when the creatinine clearance is less than 5 to 10 ml , at that time the patient come up tolerate, and he can't hope well his kidney problem, and he need support, this support we call it renal replacement therapy, with renal replacement therapy we mean either hemodialysis or peritoneal dialysis or kidney transportation. just to remember here the diabetic nephropathy is on top of the list and its the most common cause of the end stage renal disease in general, glomerular disease according to the British associated nephrology, and of course the hypertension is the second or the third according to them,, as well as the Tubulointerstitial nephritis of course including in this disease, patient who are co-experience, and they have also causes and consider to be one of the causes of chronic disease. - but plz dont forget that familiar renal diseases as alport syndrome, cystic disease or fibrous disease and others are causes of chronic disease.

Summery
very important to know that: we must know about diabetes, the most common cause of end stage renal disease and hypertension the second common cause and both coexist which means that the patient is in risk to developing the toleration of his kidney function which is might lead to end stage renal disease. -around 50% of the patients are type one diabetes, type one diabetes with is insulin dependent from which is the juvenile type. -Plz remember that its the most one, this patient has around 50% to develop chronic disease and end stage renal disease

How to approach for this patient?? this is not ur jobjust refer the patient to the internist for farther investigations, - if u see that the patient having diabetes or hypertension with or without renal impairment,,, just to know something;;; in ur clinic in the future any patient with diabetes type 2 which unnecessary to be on incident, type 2 diabetes may be on incidence or might be on oral, but type one, we never use oral hypoglycemic drugs.

for type2; at the time of diagnoses, f u see a patient with type 2 diabetes u can ask him, since when he has diabetes??, sometime he remember something, and sometime he doesnt, even he said that , I know I have diabetes since for example for the last five years or ten years, does not mean that he has a diabetes only for the last five or ten years, because he might have diabetic since long time, and the diabetes of course in most of the cases when started nobody knows. so there is incipient diabetes, clinical diabetes, which means that it's not necessary to say that this patient have diabetes since for example 2001 or 2000 or ,,, He diagnoses diabetes at that time but he doesnt know his diabetes started when. so at the time of diagnosis dont forget to send the patient for-specialist,,, including clinical assessment to his blood pressure and his eyes because these patient have retinopathy, so they have nephropathy chronically disease. -It's very important this to send ur patient for evaluation at the time of diagnosis of diabetes. And the patient with diabetes plz send him for ophthalmology exam, as well as for monitoring his blood pressure,, if it's not control to give him the drug which is appropriate as well as ask for kidney function and urinalysis. Second point: That diabetic patient, may there investigation will be normal, urinalysis normal, kidney function serum creatinine level is normal, GFR is normal or even high, and he is NO retinopathy, For type 2 this does not exclude the possibility of nephropathy as this stage, also there is no retinopathy, the vascular disease;

also there is no micro vascular disease, this patient have a possibility to have diabetic nephropathy,, why?? Because a stages 1 and 2 even stage 3, the patient has no clinical data, and the lab investigation all are normal, what is that test Which is used to predict or to disclosed if there is diabetic nephropathy?? is to ask for urine 24hour collection for microalbuminuria, albumin in the urine exceeding the normal values, normally the kidney is not excrete protein more than 20 mg per day, in diabetic nephropathy in stage3 and 2 the protein and urine might exceed this up to 300 mg, but this cannot be detected by the routine lab investigations, urine analysis alone does not exclude, by urine analysis we can detect if there is a protein in the urine.

but unfortunately this test is not sensitive to detect if there is protein exceeding less than 300 mg, and if there is less than 300mg, and above 30mg per day, means that the patient having proteinuria in form of micro albuminuria, which reflect that the patient having diabetic nephropathy.
-As I mention before that the kidneys have many roles in hemostasis of the calcium phosphorus, as well as alkalis, this way I concentrate on the calcium and phosphorous, -I would like to remind u to the function of the kidneys, again it has a role in the hemostasis of water, electrolytes and of course the blood pressure, as well as the erythropoiesis secretion, and the remaining is the calcium and phosphorous.

-the calcium as u know that its absorb from the guts, in the presence of the vD3,, which is the active form 1avD3,,, this vitamin is the active form of vitamin D, as u know that from the cholesterol and sunlight they started from there; there is 25 vitamins D3 in the liver and (1a) vitamin by (1a) hydroxyls, as well as the clout factor and the 23g guts fibroblast factors also there is convergent of 25 vitamin D to 1.25 vitamin D3, this vitamin is responsible for resorption of the calcium from the gut, and if u have problem with this with the convergent of 25 vitamin D, means that u will not have the active form of the vitamin D3, this means that u have Hypocalcemia. -in chronic disease as there loss of function of the nephron more that loss of the function of the kidney mass, there is decrease of production of this active form of vitamin D3 which leads to decrease of the absorption of the calcium, this will lead to Hypocalcemia, this is why in chronic disease when the creatinine clearance is less than 50 or 40ml/ min, there is decrease of calcium level in the serum, at the same time we have decrease of execration of the phosphorous, because of loss of the function of the kidney, this is why we have hyperphosphatemia, and the hyperphosphatemia perci might lead to farther decrease of the calcium level, so we have 2 mechanisms: 1-decrease of the absorption of the kidney leading to 2-decrease the level of the calcium.

Conclusion

in chronic diseases we have decrease production of 1a vitamin D3- which is responsible for absorption of the calcium, this is why we have Hypocalcemia, and we have also reduction of the excretion of phosphorous because of loss of the kidney mass leading to hyperphosphatemia, and both can coexist leading to farther decrease of the calcium, this is why we have Hypocalcemia, and hyperphosphatemia in chronic disease, So we have Hypocalcemia and hyperphosphatemia. Hypocalcemia perci is the stimulator for parathyroid hormone ,, leading to what?? Increase of PTH "hyperparathyroidism". This because hyperparathyroidism is secondary because Hypocalcemia, the chronically disease, we have Hypocalcemia hyperphosphatemia, and hyperparathyroidism ,, very important..

The PTH is save, or it has adverse effects, the PTH perci within the values its normal, it has a role to maintain the balance between the calcium intravascular and the bones. Now,, as the calcium is low, the PTH increasing,, why?? Because feedback mechanism,, its act on the bones, leading to resorption of the bones, this is why we have osteopenia and

this what we call hyperparathyroidism features ,, what's this features?? There is cystic lesions and others, leading to widening of the medulla of the bones and thinning of the bones and this bones become as fragile with cystic lesions, leading to fractures.. and because of vitamin D which is the deficiency of active form of vitamin D, we have problems with the bones, because there is no continuity, or mineralization of the bone, if we have boys there is growth retardation, as well as we have rickets in children, and we also have osteomalacia in adults. - in chronic disease actually; we have osteomalacia and hyperparathyroidism features, but also we have another entity we call it mix type or a dynamic bone disease. -These are symptoms seen in chronic kidney disease because as we have a chronic diseases, means that the patient might have hypertension because of the kidney as I mention before is the responsible for maintaining of the blood pressure and hemostasis or the electrolytes as well as the water,,

so usually we have anemia and of course we have

Hypocalcemia and hyperphosphatemia. As I mention before the kidney has a role to generate -1awhich is the site at the proximal tubules, where the vitamin D is responsible for absorption of the calcium. Here actually represent the normal cycle of the calcium, and this is and down the abnormal in a chronic kidney disease, how is the PTH in chronic disease and what happens to the bone

actually and the kidney as u see its not functioning well,, this is why there is no production of the active form of the vitamin D. when the patient with hyperparathyroidism or increase in PTH levels, they have big problems, that there is effect in mineralization of the bone because of the vitamin deficiency as well as because of resorption, because of the increased of PTH as well as there is along with demineralization of the bones there is also a calcium phosphorous crystal deposition everywhere, because of low calcium and high phosphorous there is inhomogeneous deposition of the calcium phosphorus in the bones as well as it might deposit in other tissues far from the bones, this lead to calcification of the tissues.. v imp In patients with chronic disease and advance chronic disease actually might have calcification of the vessels, this is why we have angina, ischemic heart diseases, we have calcified blood vessels, leading to ischemia of the peripheral vessels limbs, and also in the heart leading to conducting abnormalities as well as in the valves it might lead to obstruction of the vessels leading to sever ischemia inform of calciphylaxis" which is mean that there is dead in the tissues". It's very important to know about this,, because patients with severe form of chronic disease as the PTH is high and there is no vitamin D, and if u supply them with replacement therapy with calcium and -1a-,, this might lead to calcification here and there and a patients with a chronic disease and Hypocalcemia hyperphosphatemia, and high PTH, there are borne for fracture.. ,, this is why we should know that patients with advance stage of chronic disease, apart from osteopenia which they have and

apart from cystic lesions in form of hyper parathyroid seizures of site propose cystica and the deposition of calcium phosphorous here and there, they are also have fragile bones and they have fractures and once u have patients with fractures bone this means the mortality rate is high in this patients because it reflect that the disease so advance and the patient Is in high risk for calcification in other sites as the heart as the major vessels which might lead to obstructions of this vessels, and this we call it in adult osteomalacia, in children we call it rickets.

We have 4 types of hyperparathyroidism features:

Picture of calcified valve; we can see here this is the valve with calcification and thrombus as well, it's not uncommon to see such a problem in advance stages of chronically disease who are not good treatment. For management of chronic disease it's not your job, but u should know that u should know something regarding the chronic disease that patient with chronic disease, they are in a risk of progressed this is why we should stop as possible the acceleration of the process, to delay the progression to end stage renal disease.

How ??
if the patient is diabetic we should control his diabetes as possible.

control his blood pressure. is most of the patient has proteinuria and some degree of malnutrition, we give them protein not in the normal values, "80%"of the normal protein diet for normal people. Q:What is that thing u should do in preventing progression or to delay the progression of chronic disease? -Control the blood pressure, BECAUSE; the blood pressure control is the most important and this is the corner stone in delaying the progression of chronic disease,, -Actually the mineral bone disease what we call in chronic disease affecting the skeleton, the bones, the soft tissues, the vessels, this is why we call it before renal dystrophy. -now a days we call it mineral bone disease and renal dystrophy by which we mean that the patient having more than one feature of bone involving as osteomalacia or rickets, because the mineralization of the bone and there is osteoid without mineralization,, this seen in children and in adults. -If u see a children with growing bones or retardation, please u should know that this patient could have vitamin deficiency and one of common causes of vitamin deficiency is the chronic disease because of decrease of synthesis of the active form vitamin D,

Second; is osteomalacia in adults, this is why this patient are

prone for fractures and rupture for muscles, most of the patient have muscle weakness.

third is the dynamic bone disease which means that the PTH
is low or normal but the calcium is high and there is no synthesis of bone and the turnover is too slow, this is why it will lead to easy fracture and rupture of the muscles,

forth there is inhomogeneous mineralization of the bone as

well as the sites this is why u can see the calcification everywhere and u can see the vessels calcified, and this patient also prone for a conductive abnormalities and might develop arrhythmias and might affect their life.

Summary:
-Ur role is to detect chronic disease or elevate serum creatinine level in any patient who is candidate to any medical treatment. -Dont give any drug without knowing the kidney function of the patient because any patient might develop sever form of kidney functions impair. -Dont forget that the patient with diabetes as well as the hypertension we would like to control there diabetes , and to control blood pressure -Dont forget to ask for some lab investigations, it's one of ur target it to decrease the incidence for chronic kidney disease or end stage renal disease,, because this is v imp, our role actually is to decrease the incidence of such problem. - at the time of diagnose diabetes we must ask about some lab investigations including urinalysis , detecting for protein, Looking for protein in the urine and check their blood pressure, to ask for some lab investigations and dont forget to send the patient for ophthalmo copy to see if there is retinopathy,

because patients with type 1 diabetes up to 95% of these they might have retinopathy, for type 2 up to 70% of these patient should have retinopathy, although they might have clinical evidence or manifestation of diabetic nephropathy. For the bones Id like just to inform you that about the calcium that is usually low and the phosphorous is high and PTH is high and thats secondary hyperparathyroidism, and it will act on the bones leading to resorption of the bone and of course it might affect the muscles as well causing muscle weakness and liability for fractures, some pts especially children might have rickets and growth retardation so should give supplement of vit D and calcium. -For PTH it is always toxic in high levels also in addition to resorption of bone it may lead to etching and other manifestations. the most important with a patient with established kidney disease is to control BP, and even BP is normal you might give drugs , in diabetic nephropathy even creatinine is normal and kidney clearance is normal we might give them antihypertensive agents to decrease the intra glomerular pressure , because increase in intra glomerular pressure is the main cause to proteinuria. -Some pts we give them ACG inhibitors or ARBS although they have normal BP , our aim is to decrease intra glomerular pressure. For diabetic pts with type 1 or 2; our target is to decrease the systemic BP up to 120/80 this is max which we need 100/70 is

our target specially if there is proteinuria , if there is not 120/80 is acceptable and not more than 130/80 for pts with diabetes and nephropathy this lead to decrease IGP and ameliorate proteinuria which has toxic effect on the tubuloglomerular as well as tubules leading to delay of the progression of the disease. -chronically disease is a new term because the mineral bone disease and renal acidosis is the same, but mineral bone disease we actually added the calcification of the vessels because it is also important, even may be its more important than the bones because in the calcification of the vessels we have problems like calciphylaxis or calcification of the valves so we call it mineral blood disease.

-chronically disease and chronic renal fail is the same till

we use in most literature and in your text books you will see chronically disease but you can see chronic renal failure it is the same as acute renal failure and acute kidney injury, these are terms that we use it nowadays frequently but CRF is a valid term and chronic renal impairment as well. Q; Regarding the calcification you mentioned earlier from 90130 as we get older that level decreases so if ? As the serum creatinine level is normal for such pts in this age for adult pts, of course creatinine clearance also depend on some factors other than the ages like gender of the pt as well as the age and the body built; The CC as it above 90 ml/min this means that it is normal but less than 90 ml/min this is abnormal, with age there is loss of GFR around 10 ml/decade, some people believe above the age

of 30 some above the age of 40, but a pt who is 40 he is 80 yrs old, I expect that the GFR around 50 -55 ml/min, it is a case of chronic disease but serum creatinine level is normal, in most of these cases if you do kidney function test you will see that serum creatinine is normal although GFR is low, this is because what we call aging in the fluscelerosis, this is an entity, we can consider this pt as having chronic kidney disease stage 2, because there is structural defect if you do biopsy for this pt, you will see that there is sclerosis in glomeruli this is why these pts along with their low GFR or low creatinine clearance which reflect the loss of nephrons, means about 50% of the nephrons are functioning, the other 50% are lost; if you will do biopsy; you will see that around 50% of the nephrons are affected there is tubular loss, there is fibrosis and tubular atrophy and glomerulosclerosis, it could be not totally sclerosed it could be partially this is why the total around 50% of the total function, this entity we call it aging nephrosclerosis. As you do biopsy for the muscles for example in young pt who is 20 yrs old, and biopsy muscled for a pt who is 90 yrs old, there will be difference, there is fibrosis and loss of the actin and myosin and so on, this is why we know that these pts they maintain normal kidney function in regards to their ages, we cannot say they have chronic disease according to this because to this calcification they have chronic disease stage 2. Q:Repeating the stages??

-Stage 1 normal CC, but to call it chronic disease there is disease in the kidney, there is solitary function kidney or interstitial nephritis or diabetic nephropathy but doesnt affect the CC so CC is normal but there is defect in the function of the kidneys - Stage 2 : 89-60, Stage 3 : 59- 30, Stage 4 : 29- 15, Stage 5 : less than 15, Stage 6 : from 5-10

Im pleased If you know these :D

-creatinine clearance, stages of chronically disease -diabetes is one of the most important causes and end stage cause. -hypertension at diabetes is very bad. -coexistence and tethering is that the Ca is low Ph is high, PTH is high -Mineral bone disease with calcifications and bone deformity in children as well as growth retardation. -Fracture prognosis about pts with chronically disease or advance stage, usually the homeostasis of Ca and Ph is clinically obvious when the CC is less than 30ml/min , but actually it is started when the pt is in stage 3 when CC is less than 60ml/min. Special thanks to; malak abuaqolah Plz return to the slides,
" ,, ,, "

DONE by; asma'a almawas