Acute Kidney Injury and Chronic Kidney Disease

I. Contributor : dr. Atma Gunawan SpPD.KGH II. Learning objective

At the end of this module, student should be able to know : AKI

1. definition of AKI 2. criteria of AKI 3. the causes of AKI 4. pathogenesis of AKI 5. clinical manifestations of AKI 6. diagnosing AKI 7. pre ention and management of AKI
CKD !. definition of CKD ". criteria of CKD #. stage of CKD $. the causes of CKD %. natural history of CKD &. management to delay declining renal function '. treatment complications of CKD

8. indications for renal replacement therapy 9. indications for referral to nephrologist

III. (ethod
)his module is designed for medical students at si* semester+ and will ,e processed ,y com,ines lectures and small group discussion. I-. . er iew

Acute Kidney Injury /AKI0A123 I4)1.D5C)I.4 Acute renal failure !A"#$ has traditionall% been defined as the abru&t loss of kidne% function that results in the retention of urea and other nitrogenous waste &roducts and in the d%sregulation of e'tracellular volume and electrol%tes. (he loss of kidne% function is most easil% detected b% measurement of the serum creatinine which is used to estimate the glomerular filtration rate !)#"$. (he lack of consensus in the *uantitative definition of A"#, in &articular, has hindered clinical research since it confounds com&arisons between studies. (he Acute Dial%sis +ualit% Initiative !AD+I$ was created b% a grou& of e'&ert intensivists and ne&hrologists to develo& consensus and evidence based guidelines for the treatment and &revention of acute renal failure. "ecogni,ing the need for a uniform definition for A"#, the AD+I grou& &ro&osed a consensus graded definition, called the "I#L- criteria. A modification of the "I#L- criteria was subse*uentl% &ro&osed b% the Acute Kidne% Injur% .etwork !AKI.$, which included the AD+I grou& as well as re&resentatives from other ne&hrolog% and intensive care societies . /ecause of these initiatives, the term acute kidne% injur% !AKI$ was &ro&osed to re&resent the entire s&ectrum of acute renal failure. AKI4 C1I)61IA (he AKI. !Acute Kidne% Injur% .etwork$, which re&resentatives from ne&hrolog% and intensive care societies, &ro&osed diagnostic criteria for A"# and a staging s%stem. (he &ro&osed diagnostic criteria for A"# are an abru&t !within 01 hours$ absolute increase in the serum creatinine concentration of 2 3.4 mg5dL !67.0 micromol5L$ from baseline, a &ercentage increase in the serum creatinine concentration of 2 83 &ercent, or oliguria of less than 3.8 mL5kg &er hour for more than si' hours. (he addition of an absolute change in serum creatinine of 2 3.4 mg5dL is based on e&idemiologic data that have demonstrated an 13 &ercent increase in mortalit% risk associated with changes in serum creatinine concentration of as little as 3.4 to 3.8 mg5dL. Including a time constraint of 01 hours is based u&on data that showed that &oorer outcomes were associated with small changes in the creatinine when the rise in creatinine was observed within 60 to 01 hours

(wo additional caveats were &ro&osed b% the AKI. grou&: (he diagnostic criteria should be a&&lied onl% after volume status had been o&timi,ed 9rinar% tract obstruction needed to be e'cluded if oliguria was used as the sole diagnostic criterion. A flaw with the last caveat is that, according to the current definition, AKI would still be used to describe the &atient with acute urinar% tract obstruction and an acute increase in serum creatinine. Classification0staging system for acute 7idney injury /AKI4 criteria38 : . Increase in serum creatinine of more than or e*ual to 3.4 mg5dL !67.0 mircomol5L$ or increase to more than or e*ual to :83 to 633 &ercent !:.8; to 6;fold$ from baseline or urine out&ut less than 3.8 mL5kg &er hour for more than 7 hours. 6 . Increase in serum creatinine to more than 633 to 433 &ercent !<6; to 4; fold$ from baseline or urine out&ut less than 3.8 mL5kg &er hour for more than :6 hours. 4 . Increase in serum creatinine to more than 433 &ercent !<4;fold$ from baseline !or serum creatinine of more than or e*ual to 0.3 mg5dL =480 micromol5L> with an acute increase of at least 3.8 mg5dL =00 micromol5L>$ or urine out&ut less than 3.4 mL5kg &er hour for 60 hours or anuria for :6 hours. ? (he diagnostic criteria should onl% be a&&lied after volume status has been o&timi,ed. @nl% one criterion !creatinine or urine out&ut$ has to be fulfilled to *ualif% for a stage. 633 to 433 &ercent increase A 6; to 4;fold increase. PA)H.G646SIS A4D 6)I.9.G: (he causes of acute renal disease can be related to the renal anatom% most affected b% the disorder as follows: Bascular, )lomeruli ,"enal tubule, 9rinar% tract . An% &rocess that interferes with an% of these structures and5or functions can cause renal disease. (he causes of AKI can therefore be categori,ed as &rerenal, renal, or &ostrenal. Crerenal Crerenal a,otemia results from either: Bolume de&letion due to bleeding !surger%, trauma, gastrointestinal bleeding$, gastrointestinal !vomiting, diarrhea$, urinar% !diuretics, diabetes insi&idus$, or cutaneous losses !burns$. Decreased effective arterial &ressure and5or effective circulating volume seen in heart failure, shock, or cirrhosis Intrinsic renal disorders Intrinsic renal disease includes disorders that involve the renal vascular, glomerular, and5or tubular5interstitial &atholog%. 3

Bascular Bascular causes of AKI include thrombosis !arterial and venous$, hemol%tic;uremic s%ndrome, malignant h%&ertension, and vasculitis. )lomerular (he &rinci&al glomerular cause of AKI is acute glomerulone&hritis, which is commonl% &ostinfectious. AKI can be observed with most of the glomerulone&hritides that can occur in childhood. (ubular and interstitial disease Acute tubular necrosis !A(.$ results from ischemia due to decreased renal &erfusion or injur% from tubular ne&hroto'ins. All causes of &rerenal a,otemia can &rogress to A(. if renal &erfusion is not restored and5or ne&hroto'ic insults are not withdrawn (he administration of ne&hroto'ic agents, including aminogl%cosides,methicillin, beta;lactam, am&hotericin /, and contrast agents, is a common cause of tubular disease. Currentl%, the most common drug causes of AI. include: .DAIDs, including selective C@E;6 inhibitors. Cenicillins and ce&halos&orins "ifam&in Dulfonamides, including trimetho&rim; sulfametho'a,ole and, much less often, furosemide, bumetanide, thia,ide; t%&e diuretics, Ci&roflo'acin and, Cimetidine, Allo&urinol, Croton &um& inhibitors. Costrenal Costrenal AKI is due to bilateral urinar% tract obstruction unless there is a solitar% kidne%. In neonates, urinar% tract obstruction, due to &osterior urethral valves is the most common cause of &ostrenal failure. Causes of AKI Deven studies &rimaril% from Asia !India =4 re&orts>, .ew Fealand =: trial>, Dinga&ore =: trial>$ that re&orted the following were the most common causes of A"# ranked in order of incidence: Acute tubular necrosis !A(.$, !64 &ercent$ Gemol%tic uremic s%ndrome !G9D$, !6: &ercent$ )lomerulone&hritis !:4 &ercent$ Intrinsic renal disease !H &ercent$, causes not s&ecified Costo&erative !I &ercent$ De&sis !7 &ercent$ Ischemia5&rerenal !0.8 &ercent$ 9rinar% tract obstruction !4 &ercent$ Jiscellaneous causes !:4.1 &ercent$ including metabolic disorders, renal venous thrombosis, he&atorenal s%ndrome, com&lication of organ trans&lantation. C9I4ICA9 P16S64)A)I.4 A careful histor% and &h%sical e'amination can fre*uentl% identif% events and5or disease &rocesses that underlie AKI and suggest an underl%ing diagnosis: A histor% of vomiting, diarrhea, hemorrhage, se&sis and5or decreased oral intake resulting in h%&ovolemia, associated with decreased urine out&ut suggests AKI due to &rerenal disease or A(.. Ch%sical e'amination findings that include tach%cardia, dr% mucous membranes, sunken e%es, orthostatic blood &ressure changes, and decreased skin turgor suggest h%&ovolemia, resulting in AKI due to &rerenal disease or A(.. 4

/lood% diarrhea with oliguria !defined as less than 833 mL5:.I4 m6 &er da% in children and less than 3.8 mL5kg &er hour in infants$ or anuria !absent urine$ is consistent with the hemol%tic;uremic s%ndrome. A histor% of &har%ngitis or im&etigo, a few weeks &rior to the onset of gross hematuria suggests &ost;infectious glomerulone&hritis. .e&hrotic s%ndrome, heart failure, and liver failure ma% result in edema and other signs of s&ecific organ d%sfunction. Gemo&t%sis in the &resence of renal im&airment suggests a diagnosis of &ulmonar%;renal s%ndrome, which includes )ood&astureKs s%ndrome or LegenerKs granulomatosis. Dkin findings, such as &ur&ura, malar rash, or &etechiae, and5or joint &ain favor a diagnosis of s%stemic vasculitis, such as s%stemic lu&us er%thematosus or Genoch DchMnlein In the hos&ital, A(. resulting from h%&otension !due to se&sis or intrao&erative events$ or from the administration of ne&hroto'ic medications !such as aminogl%cosides or am&hotericin;/$ is the common cause of AKI . 6-A95A)I.4 A4D DIAG4.SIS In addition to a careful histor% and &h%sical e'amination, the initial evaluation includes an estimation of the glomerular filtration rate, e'amination of the urine, and the use of other modalities. Deveral formulas that utili,e easil% obtained values have been develo&ed that hel& estimate the )#" in &atients with chronic renal failure. (he most common methods utili,ed to estimate the )#" are the serum creatinine concentration, the creatinine clearance, or estimation e*uations based u&on the serum creatinine: such as the Cockcroft;)ault e*uation and Jodification of Diet in "enal Disease !JD"D$ Dtud% e*uations. In children, the most commonl% used formula to estimate creatinine clearance is the Dchwart, formula . -stimation of the glomerular filtration rate !)#"$, usuall% b% the serum creatinine concentration, is used clinicall% to assess the degree of renal im&airment and to follow the course of the disease. It is im&ortant to reali,e that estimation of the )#" has no diagnostic utilit%. -ven if absolute values remain in the normal range, a se*uential increase in the serum creatinine concentration strongl% suggests a decrease in the glomerular filtration rate. Creatinine clearance Creatinine is derived from the metabolism of creatine in skeletal muscle and from dietar% meat intakeN it is released into the circulation at a relativel% constant rate and has a stable &lasma concentration. Creatinine is freel% filtered across the glomerulus and is neither reabsorbed nor metaboli,ed b% the kidne%. Gowever, a&&ro'imatel% :3 to 03 &ercent of urinar% creatinine is derived from tubular secretion b% the organic cation secretor% &athwa%s in the &ro'imal tubule

If the effect of secretion is ignored, then all of the filtered creatinine !e*ual to the &roduct of the )#" and the serum creatinine concentration =DCr>$ will be e'creted !e*ual to &roduct of the urine creatinine concentration =9Cr> and the urine flow rate$. (hus: G21 * SCr ; 5Cr * G21 ; <5Cr * -=0SCr (his formula is called the creatinine clearance . (he creatinine clearance is usuall% determined from a 60 hour urine collection, since shorter collections tends to give less accurate results. Du&&ose that the following results are obtained in a 73 kg woman: SCr 5Cr (hus: CCr ; ; ; ; !." mg0d9 /!>& ?mol093 !>> mg0d9 /@@>> ?mol093 !." 90day <!>> * !."=0!." ; !>> 90day

(his value has to be multi&lied b% :333 to convert into mL and then divided b% :003 !the number of minutes in a da%$ to convert into units of mL5min. CCr ; <!>> * !>>>=0!$$> ; '> m90min

A &atientKs creatinine clearance should ideall% be adjusted to bod% surface area !/DA$ when com&aring to normal values. As an e'am&le, a creatinine clearance of I3 mL5min in a small woman with a weight and height of 83 kg and :73 cm, who has a /DA of :.8, is corrected to a bod% surface area of :.I4 m6 as follows: CCr * !.'#0ASA ; <'> m90min * !.'#= 0 !.% ; @> m90min per !.'# m" In turn, for a large &erson with a bod% surface area of :.H, the adjusted CCl would be 70 mL5min &er :.I4 m6. Cockcroft-Gault equation (he Cockcroft;)ault e*uation allows the creatinine clearance to be estimated from the serum creatinine in a &atient with a stable serum creatinine: CCr /m90min3 /!$> B age3 * lean ,ody weight <7g= Cr <mg0d9= * '" (his formula takes into account the increase in creatinine &roduction with increasing weight, and the decline in creatinine &roduction with age. #or 6 ;

women, the formula re*uires multi&lication b% 3.18 to account for smaller muscle mass com&ared to men. (he )#" can be estimated b% using the Dchwart, formula, which is based u&on serum creatinine, age, height, and in adolescents, the gender of the &atient . G21 ; 7 C Height /cm3 0 Screat Geight re&resents the bod% height measured in centimeters, and Dcreat is the serum creatinine in mg5dl. (he constant k is directl% &ro&ortional to the muscle com&onent of bod%, and varies with age. (he value for k is 3.44 in &remature infants through the first %ear of life, 3.08 for term infants through the first %ear of life, 3.88 in children and adolescent girls, and 3.I in adolescent bo%s. Serum BUN/creatinine ratio In adults and older children, the serum /9.5creatinine ratio is normal at :3 to :8:: in A(., and ma% be greater than 63 : : in &rerenal disease due to the increase in the &assive reabsor&tion of urea that follows the enhanced &ro'imal trans&ort of sodium and water. (hus, a high ratio is highl% suggestive of &rerenal disease. (his ratio is not useful in infants and smaller children as their serum creatinine levels are much lower. Urinalysis (he urinal%sis is the most im&ortant noninvasive test in the diagnostic evaluation, since characteristic findings on microsco&ic e'amination of the urine sediment strongl% suggest certain diagnoses . As e'am&les: A normal or near;normal urinal%sis, characteri,ed b% few cells with little or no casts or &roteinuria, suggests &rerenal disease, urinar% tract obstruction, and some cases of acute tubular necrosis !A(.$. Judd% brown granular casts and e&ithelial cell casts are highl% suggestive of A(.. (he finding of a red cell cast is diagnostic of glomerulone&hritis, while the &resence of &roteinuria is generall% indicative of some form of glomerular disease. (he concurrent &resence of hematuria with red cell casts, d%smor&hic red cells, heav% &roteinuria, or li&iduria can also hel& subclassif% &atients into those with an active One&hriticO sediment. (his is commonl% associated with AKI due to glomerulone&hritis. C%uria with white cell and granular or wa'% casts and var%ing levels of &roteinuria is suggestive of tubular or interstitial disease or urinar% tract infection. Lhite cells and white cell casts can also be seen in acute glomerulone&hritis, &articularl% &ostinfectious glomerulone&hritis. In this setting, however, there are also other signs of glomerular disease, such as hematuria, red cell casts, and &roteinuria.

Gematuria and &%uria with no or variable casts !e'cluding red cell casts$ ma% be seen in acute interstitial ne&hritis, glomerular disease, vasculitis, obstruction, and renal infarction. Urine sodium e concentration is effective volume 43 to 03 m-*5L res&ectivel%. cretion Lith AKI, measurement of the urine sodium hel&ful in distinguishing A(. from &rerenal AKI due to de&letion. (he urine sodium concentration is usuall% above and below :3 m-*5L in the former and latter conditions,

#ractional e'cretion of sodium !#-.a$ (he effect of variations in urine volume can be eliminated b% calculating the #-.a : 264a /percent3 ; 54a * PCr * P4a * 5Cr !>>

where 9Cr and CCr are the urine and serum creatinine concentrations, res&ectivel%, and 9.a and C.a are the urine and serum sodium concentrations, res&ectivel%. (he #-.a is a screening test that differentiates between &rerenal AKI and A(. in children. A value below : &ercent suggests &rerenal disease, where the reabsor&tion of almost all of the filtered sodium re&resents an a&&ro&riate res&onse to decreased renal &erfusion. A value between : and 6 &ercent ma% be seen with either disorder. A value above 6 &ercent usuall% indicates A(.. In newborns, &rerenal disease and A(. are associated with #-.a values of less than 6.8 &ercent and greater than 6.8 to 4.8 &ercent, res&ectivel%, because of their decreased abilit% to reabsorb sodium. Urine osmolality Loss of concentrating abilit% is an earl% and almost universal finding in A(. with the urine osmolalit% usuall% being below 483 mosmol5kg. In contrast, a urine osmolalit% above 833 mosmol5kg is highl% suggestive of &rerenal disease. !es"onse to #olume re"letion 9nless contraindicated, a child with a clinical histor% consistent with fluid loss !such as vomiting and diarrhea$, a &h%sical e'amination consistent with h%&ovolemia !h%&otension and tach%cardia$, and5or oliguria should be administered intravenous fluid thera&%. (his fluid challenge attem&ts to identif% &rerenal failure that can &rogress to A(. if not treated &rom&tl%. Gowever, such fluid infusion is contraindicated in those with obvious volume overload or heart failure. Commonl% used fluids are cr%stalloid solutions, such as normal saline !63 mL5kg$ administered over 63 to 43 minutes, which ma% be re&eated. "estoration of ade*uate urine flow and im&rovement in renal function with 8

fluid resuscitation is consistent with &rerenal disease. Gowever, if urine out&ut does not increase and renal function fails to im&rove with the restoration of intravascular volume, invasive monitoring ma% be re*uired to ade*uatel% assess the fluid status and hel& guide further thera&%. Additional laborator% measurements Com"lete $lood count Devere microangio&athic hemol%tic anemia associated with thromboc%to&enia in the setting of AKI confirms the diagnosis of G9D . Devere hemol%sis, whether drug;induced or secondar% to hemoglobino&athies, ma% also result in A(. due to massive hemoglobinuria. !enal imaging "enal ultrasonogra&h% should be &erformed in all children with AKI of unclear etiolog%. It can document the &resence of one or two kidne%s, delineate renal si,e, and hel& surve% renal &arench%ma . It is &articularl% useful in diagnosing urinar% tract obstruction or occlusion of the major renal vessels. !enal $io"sy A renal bio&s% is most commonl% obtained when noninvasive evaluation has been unable to establish the correct diagnosis . Biomarkers /iomarkers have been identified that beginning stages of AKI. 9rinar% levels of neutro&hil li&ocalin !.)AL$ were found to be elevated 6 hours develo&ed AKI . In addition to .)AL, interlukin;:1 has earl% marker of AKI . ma% identif% in the gelatinase;associated before subse*uentl% been re&orted as an

P16-64)I.4 .2 AKI )eneral measures to hel& &revent AKI include close monitoring of serum levels of ne&hroto'ic drugs, ade*uate fluid re&letion in those with h%&ovolemia, fluid challenge if sus&ected &rerenal h%&ovolumia, and aggressive h%dration and alkalini,ation of the urine &rior to chemothera&%. (A4AG6(64) .2 AKI (he basic &rinci&les of the general management of acute kidne% injur% !AKI$ include: - Jaintenance of electrol%te and fluid balance - Ade*uate nutritional su&&ort Avoidance of life;threatening com&lications - (reatment of the underl%ing cause %y"erkalemia G%&erkalemia can be as%m&tomatic or severe enough to constitute a medical emergenc%. As the e'tracellular &otassium levels increase in AKI, the gradient and membrane &otential are affected, resulting in the clinical signs of muscle weakness and cardiac arrh%thmias. -lectrocardiogra&hic findings associated with h%&erkalemia consist of &eaked ( waves, flattened C waves, increased C" interval, and widening of the +"D.

/rad%cardia, su&raventricular or ventricular tach%cardia, and ventricular fibrillation ma% occur (he following modalities are for treatment of severe h%&erkalemia !above I me*5L$. - Dtabili,ation of the cardiac membrane with the intravenous calcium !calcium gluconate :3 &ercent solution in a dose 3.8 to :.3 mL &er kilogram intravenousl% over 8 to :8 minutes$. Cromotion of &otassium movement from the e'tracellular fluid !-C#$ into the cells via three different thera&ies: :. Administration of intravenous glucose and insulin !3.8 to :.3 g of glucose &er kilogram over 43 minutes and 3.: unit of insulin &er kilogram intravenousl% or subcutaneousl%$N 6. Administration of intravenous sodium bicarbonate !in a dose of : to 6 millie*uivalent &er kilogram over 43 to 73 minutes$ 4. Administration of beta agonists, such as albuterol 8 mg, via nebuli,ation (he above modalities onl% transientl% lower the &lasma &otassium concentrationN as a result, additional thera&% is re*uired to remove &otassium from the bod%. (hus, ka%e'alate, an ion e'change resin, can be used to effect a net elimination of &otassium, at a dose of : gram &er kilogram orall% or rectall%. #or &atients who have mild to moderate h%&erkalemia !serum &otassium levels greater than 7.3 m-*5L and less than I.3 m-*5L, and who are as%m&tomatic without electrocardiogra&hic changes$, ka%e'alate thera&% ma% be useful to &revent further increases in serum &otassium levels. Acidosis In AKI, not onl% is acid e'cretion im&aired, acid &roduction fre*uentl% is increased on account of underl%ing comorbid conditions such as shock and se&sis. Administration of sodium bicarbonate should be done onl% in life;threatening situations in which ma'imal res&irator% com&ensation is inade*uate, and5or the acidosis is contributing to h%&erkalemia. In cases of severe or &rogressive acidosis following shock, serious infections or other h%&ercatabolic states, su&&lemental bicarbonate ma% be re*uired to correct and maintain arterial &G above I.6 until the underl%ing disease is controlled. Catients with serum bicarbonate levels that are above :0 m-*5L or with arterial &G greater than I.6 do not re*uire intervention. Administer : m-* of intravenous sodium bicarbonate5kg of bod% weight over 43;73 minutes, and monitor arterial &G and bicarbonate levels to determine further thera&%. Intravascular volume /ased u&on the underl%ing cause, comorbid conditions, and &ossible &revious thera&%, ma% be h%&ovolemic, euvolemic, or h%&ervolemic !including &ulmonar% edema and heart failure$.

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&luid If clinical histor% and &h%sical e'am consistent with fluid loss, and5or oliguria re*uires immediate intravenous fluid thera&% in an attem&t to restore renal function and &erha&s &revent ischemic renal injur%. Commonl% used fluids are cr%stalloid solutions, such as normal saline !63 mL5kg$ administered over 63 to 43 minutes, which ma% be re&eated. Catient with oliguria, overload volume, or heart failure, re*uire immediate fluid removal and5or fluid restriction. In such cases a trial of furosemide !6 to 8 mg5kg &er dose$ ma% be attem&ted to induce a diuresis and convert oliguric to non;oliguric renal failure . Gowever, diuretics should not be continued in an unres&onsive &aients. If a diuresis does not ensue and5or the &atient has evidence of fluid overload with &ulmonar% edema, renal re&lacement thera&% should be initiated. Nutrition AKI is associated with marked catabolism, and inade*uate nutrition can dela% recover% of the &atientKs renal function. Infants should receive at least maintenance calories !:63 Kcal5kg &er da%$. Adult should receive at least calories 03 Kcal5kg &er da%, &rotein :,6 P :,8 gram5kg &er da%. !enal re"lacement thera"y initiated for the following : "enal re&lacement thera&% in AKI should be

Digns and s%m&toms of uremia s%m&toms that include &ericarditis, neuro&ath% or an otherwise une'&lained decline in mental status regardless of the serum /9. or creatinine concentration. A,otemia !/9. greater than 13 to :33 mg5dL =6H to 47 mmol5L>$. Devere fluid overload as manifested b% h%&ertension, &ulmonar% edema or heart failure that is refractor% to su&&ortive medical thera&%. Devere electrol%te abnormalities including h%&erkalemia, h%&ernatremia, h%&onatremia, and acidosis that are refractor% to su&&ortive medical thera&%. .eed for intensive nutritional su&&ort in a child with oliguria or anuria.

Available renal re&lacement modalities for the management of acute kidne% injur% include the following: Gemodial%sis, Ceritoneal dial%sis, Continuous renal re&lacement thera&% !C""($ (he use of renal re&lacement thera&% to remove fluid and solute of to'ins until renal recover%

Chronic Kidney Disease

4A)51A9 HIS).1: .2 164A9 DIS6AS6 (he initial injur% to the kidne% ma% result in a variet% of clinical manifestations, ranging from as%m&tomatic hematuria to renal failure re*uiring dial%sis. Jan% individuals full% recover and subse*uentl% suffer from little or no se*uelae. Coststre&tococcal glomerulone&hritis in children, for e'am&le, most fre*uentl% has a long;term benign &rognosis. /% com&arison, some &atients, such as those with lu&us ne&hritis, e'&erience re&eated and chronic insults to the renal &arench%ma,

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thereb% resulting in lasting damage. #urthermore, others in whom the initial disease is either inactive or cured ma% still develo& &rogressive renal disease due to hemod%namic and other mechanisms. In addition to variations in the activit% of the individual diseases, these different manifestations are &artl% due to how the kidne% res&onds to injur%. (he kidne% is able to ada&t to damage b% increasing the filtration rate in the remaining normal ne&hrons, a &rocess called ada&tive h%&erfiltration. As a result, the &atient with mild renal insufficienc% often has a normal or near; normal serum creatinine concentration. Additional homeostatic mechanisms !most fre*uentl% occurring within the renal tubules$ &ermit the serum concentrations of sodium, &otassium, calcium, and &hos&horous and the total bod% water to also remain within the normal range, &articularl% among those with mild to moderate renal failure. !Dee OAssessment of kidne% function: Derum creatinineN /9.N and )#"O$. Ada&tive h%&erfiltration, although initiall% beneficial, a&&ears to result in long; term damage to the glomeruli of the remaining ne&hrons, which is manifest b% &roteinuria and &rogressive renal insufficienc%. (his &rocess a&&ears to be res&onsible for the develo&ment of renal failure among those in whom the original illness is either inactive or cured. (he institution of measures to hel& &revent this &rocess, such as antih%&ertensive thera&% with an angiotensin converting en,%me inhibitor or an angiotensin II rece&tor blocker, ma% slow &rogressive disease and even &reserve renal function. If these modalities are effective, the benefit is likel% to be greatest if begun before a great deal of irreversible scarring has occurred. !Dee ODecondar% factors and &rogression of chronic kidne% diseaseO$. (he gradual decline in function in &atients with chronic kidne% disease !CKD$ is initiall% as%m&tomatic. Gowever, as &reviousl% mentioned, different signs and s%m&toms ma% be observed with advanced renal d%sfunction, including volume overload, h%&erkalemia, metabolic acidosis, h%&ertension, anemia, and bone disease. (he onset of end;stage renal disease results in a constellation of signs and s%m&toms referred to as uremia. Janifestations of the uremic state include anore'ia, nausea, vomiting, &ericarditis, &eri&heral neuro&ath%, and central nervous s%stem abnormalities !ranging from loss of concentration and letharg% to sei,ures, coma, and death$. .o direct correlation e'ists between the absolute serum levels of blood urea nitrogen !/9.$ or creatinine, and the develo&ment of these s%m&toms. Dome &atients have relativel% low levels !eg, a /9. of 73 mg5dL =6:.0 mmol5L> in an older &atient$ but are markedl% s%m&tomatic, while others have marked elevations !eg, a /9. of :03 mg5dL =83 mmol5L>$ but remain as%m&tomatic. (o continue life, uremic &atients re*uire the institution of renal re&lacement thera&% with hemodial%sis, &eritoneal dial%sis, or renal trans&lantation.

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D62I4I)I.4S A4D C9ASSI2ICA)I.4 (he definition, classification and guideline of chronic kidne% were &ro&osed from the .ational Kidne% #oundation of the 9nited Dtates through its Kidne% Disease @utcomes +ualit% Initiative !K5D@+I$ &rogram. (hese guidelines have been reviewed and acce&ted internationall%. (he K5D@+I working grou& defined chronic kidne% disease as: :. -vidence of structural or functional kidne% abnormalities !abnormal urinal%sis, imaging studies, or histolog%$ that &ersist for at least three months, with or without a decreased )#" !as defined b% a )#" of less than 73 mL5min &er :.I4 m6$. (he most common manifestation of kidne% damage is &ersistent albuminuria, including microalbuminuria. 6. @r decreased )#", with or without evidence of kidne% damage. /ased u&on these definitions, the following is the recommended classification of chronic kidne% disease b% stage and the estimated &revalence within the 9nited Dtates of each stage, as determined b% a .ational Gealth and .utrition -'amination Durve% !.GA.-D$ &erformed in :HHH to 6330 : Dtage : disease is defined b% a normal )#" !greater than H3 mL5min &er :.I4 m6$ and &ersistent albuminuria. - Dtage 6 disease is a )#" between 73 to 1H mL5min &er :.I4 m6 and &ersistent albuminuria. - Dtage 4 disease is a )#" between 43 and 8H mL5min &er :.I4 m6. - Dtage 0 disease is a )#" between :8 and 6H mL5min &er :.I4 m6. - Dtage 8 disease is a )#" of less than :8 mL5min &er :.I4 m6 or end; stage renal disease. (he K5D@+I guidelines have also suggested that microalbuminuria alone that &ersists for more than three months falls within the definition of chronic kidne% disease in &atients without diabetes. G6461A9 (A4AG6(64) .2 CH1.4IC KID46: DIS6AS6 (he general management of the &atient with chronic kidne% disease involves the following issues : (reatment of reversible causes of renal d%sfunction Creventing or slowing the &rogression of renal disease (reatment of the com&lications of renal d%sfunction Identification and ade*uate &re&aration of the &atient in whom renal re&lacement thera&% will be re*uired

1e ersi,le causes of renal dysfunction &atients with chronic renal disease with a recent decrease in renal function ma% be suffering from an underl%ing reversible &rocess, which if identified and corrected ma% result in the recover% of function. 13

'ecreased renal "erfusion G%&ovolemia !such as vomiting, diarrhea, diuretic use, bleeding$, h%&otension !due to m%ocardial d%sfunction or &ericardial disease$, infection !such as se&sis$, and the administration of drugs which lower the )#" !such as nonsteroidal antiinflammator% drugs =.DAIDs> and AC- inhibitors$ are common causes of &otentiall% reversible declines in renal function. Urinary tract o$struction 9rinar% tract obstruction should alwa%s be considered in the &atient with une'&lained worsening renal function. "enal ultrasonogra&h% is often &erformed to e'clude urinar% tract obstruction in &atients with an une'&lained elevation in the serum creatinine. Slowing the rate of progression Dtudies in e'&erimental animals and humans suggest that &rogression in chronic renal disease ma% be due at least in &art to secondar% factors that are unrelated to the activit% of the initial disease. (he major factors are thought to be intraglomerular h%&ertension and glomerular h%&ertro&h% !which are &rimaril% res&onsible for the ada&tive h%&erfiltration described above$, leading to glomerular scarring !glomerulosclerosis$. (he major histologic manifestation of hemod%namicall%;mediated renal injur% is secondar% focal segmental glomerulosclerosis . (hus, &roteinuria t%&icall% occurs in &atients with &rogressive chronic kidne% disease. Aggressive goals are recommended for both &roteinuria and blood &ressure. Antih%&ertensive thera&% is given for both renal &rotection and cardiovascular &rotection, since chronic kidne% disease is associated with a marked increased in cardiovascular risk. A reduction in &rotein e'cretion to less than 833 to :333 mg5da% A reduction in blood &ressure to less than :43513 mmGg. (hese aggressive goals will, in most &atients, re*uire thera&% with multi&le drugs. AC- inhibitors and A"/s has benefit to reduce &roteinuria, reduce blood &ressure, slowing decline in renal function. Low &rotein diet. "estrict &rotein intake to 3.1 to :.3 g5kg &er da% of high biologic value &rotein, with the lower value !3,7 to 3,I8 g5kg &erda%$ used in &atients with &rogressive chronic kidne% disease. Calories should be &rovided a&&ro'imatel% 43 to 48 kcal5kg &er da%. /oth h%&erli&idemia and metabolic acidosis should be treated, in &art because there is some evidence that the% ma% enhance the rate of &rogression of the renal. Dmoking cessation should be encouraged, with smoking sto&&age being associated with a reduced rate of &rogression of chronic kidne% disease.

14

)reatment of the complications of renal dysfunction A wide range of disorders ma% develo& as a conse*uence of the loss of renal function. (hese include disorders of fluid and electrol%te balance, such as volume overload, h%&erkalemia, metabolic acidosis, and h%&er&hos&hatemia, as well as abnormalities related to hormonal or s%stemic d%sfunction, such as anore'ia, nausea, vomiting, fatigue, h%&ertension, anemia, malnutrition, h%&erli&idemia, and bone disease. (olume o#erload Dodium and intravascular volume balance are usuall% maintained via homeostatic mechanisms until the )#" falls below :3 to :8 mL5min. Gowever, the &atient with mild to moderate chronic kidne% disease, des&ite being in relative volume balance, is less able to res&ond to ra&id infusions of sodium and is therefore &rone to fluid overload. Catients with chronic kidne% disease and volume overload generall% res&ond to the combination of dietar% sodium restriction and diuretic thera&%, usuall% with a loo& diuretic given dail%. In case of severe volume overload , furosemide !6 to 8 mg5kg &er dose$ ma% be attem&ted to induce a diuresis and convert oliguric to non;oliguric renal failure %y"erkalemia h%&erkalemia generall% develo&s in the &atient who is oliguric or who has an additional &roblem such as a high &otassium diet, increased tissue breakdown, or h%&oaldosteronism !due in some cases to the administration of an AC- inhibitor or A"/$. G%&erkalemia due to AC- inhibitor or A"/ thera&% is most likel% to occur in &atients in whom the serum &otassium concentration is elevated or in the high normal range &rior to thera&%. In this setting, institution of a low;&otassium diet or concurrent use of a loo& diuretic !to increase urinar% &otassium losses$ often ameliorates the degree of h%&erkalemia. In selected &atients, low dose Ka%e'alate !8 grams with each meal$ can be used to lower the serum &otassium concentration without the side effects associated with larger doses. !see treatment h%&erkalemia in subject of AKI$. )eta$olic acidosis (here is an increasing tendenc% to retain h%drogen ions among &atients with chronic renal disease . (his can lead to a &rogressive metabolic acidosis with the serum bicarbonate concentration tending to stabili,e between :6 and 63 me*5L, and rarel% falling below :3 me*5L Le recommend alkali thera&% to maintain the serum bicarbonate concentration above 64 me*5L. If alkali is given, sodium bicarbonate !in a dail% dose of 3.8 to : me*5kg &er da%$ is the agent of choice. !see also treatment of metabolic acidosis in subject of AKI$. %y"er"hos"hatemia A tendenc% toward &hos&hate retention begins earl% in renal disease, due to the reduction in the filtered &hos&hate load. Although this &roblem is initiall% mild with h%&er&hos&hatemia being a relativel% late

15

event, &hos&hate retention is intimatel% related to the common develo&ment of secondar% h%&er&arath%roidism. #rom the view&oint of calcium and &hos&hate balance, the h%&ersecretion of &arath%roid hormone !C(G$ is initiall% a&&ro&riate, since C(G can correct both h%&er&hos&hatemia and h%&ocalcemia. As a result, &hos&hate balance and a normal serum &hos&hate concentration are generall% maintained in &atients with a )#" of greater than 43 mL5min. (he &rice &aid is secondar% h%&er&arath%roidism and the develo&ment of renal osteod%stro&h%. Dietar% &hos&hate restriction ma% limit the develo&ment of secondar% h%&er&arath%roidism in &atients with chronic kidne% disease. @nce the )#" falls below 68 to 43 mL5min, the addition of oral &hos&hate binders are usuall% re*uired to &revent h%&er&hos&hatemia. @ne of the &referred agents to bind intestinal &hos&hate is calcium salts, of which one of the most widel% used is calcium carbonate. In &atients with stage 4 to 8 CKD, the K5D@+I guidelines suggest that total elemental calcium intake !including both dietar% calcium intake and calcium;based &hos&hate binders$ should not e'ceed 6,333 mg5da%. @ther &hos&hate binder are sevelamer and lanthanum %y"ertension G%&ertension is &resent in a&&ro'imatel% 13 to 18 &ercent of &atients with chronic kidne% disease . (reating h%&ertension can both slow the &rogression of &roteinuric CKD and reduce the rate of cardiovascular com&lications. (he desired degree of blood &ressure control can usuall% be safel% achieved with combined thera&% which usuall% begins with an AC- inhibitor or angiotensin II rece&tor blocker and a diuretic. Bolume e'&ansion, often in the absence of overt edema, contributes to the elevation in blood &ressure in most forms of chronic renal disease. As a result, before other medications are added, the dose of diuretics should be increased until the blood &ressure is normali,ed or the &atient has attained Odr% weightO which, in the &resence of &ersistent h%&ertension, is defined as the weight at which further fluid loss will lead either to s%m&toms !fatigue, orthostatic h%&otension$ or to decreased tissue &erfusion as evidenced b% an otherwise une'&lained elevation in the /9. and &lasma creatinine concentration. A loo& diuretic is recommended for the treatment of h%&ertension and edema in &atients with chronic kidne% disease. (he thia,ide diuretics in conventional dosage become less effective as monothera&% when the )#" falls below 63 mL5min. (he% do, however, &roduce an additive effect when administered with a loo& diuretic for refractor% edema. Le recommend a blood &ressure goal of less than :43513 mmGg, which is consistent with Q.C I and the K5D@+I Clinical Cractice )uidelines on h%&ertension and antih%&ertensive agents in chronic kidne% disease . Gowever, evidence from the Jodification of Diet in "enal Disease stud%, the AADK trial, and a meta;anal%sis from the AC- inhibition and Crogressive "enal 16

Disease !AIC"D$ stud% grou& suggest that an even lower s%stolic &ressure ma% be more effective in slowing &rogressive renal disease in &atients with a s&ot urine total &rotein;to;creatinine ratio 2 :333 mg5g !which re&resents &rotein e'cretion of greater than :333 mg5da%$ . Caution is advised about lowering the s%stolic blood &ressure below ::3 mmGg. Anemia (he anemia of chronic kidne% disease is, in most &atients, normoc%tic and normochromic, and is due &rimaril% to reduced &roduction of er%thro&oietin b% the kidne% !a &resumed reflection of the reduction in functioning renal mass$, and to shortened red cell survival. Anemia is a common feature in man% &atients with chronic kidne% disease who do not %et re*uire dial%sis, with anemia becoming increasingl% common as glomerular filtration rates !)#"s$ decline below 73 mL5min &er :.I4 m6 . As stated in the 6337 K5D@+I guidelines, the evaluation of anemia in those with CKD should begin when the Ggb level is less than :6 g5dL in females, and Ggb levels of less than :4.8 g5dL in adult males. (he evaluation of &atients should therefore include red blood cell indices, absolute reticuloc%te count, serum iron, total iron binding ca&acit%, &ercent transferrin saturation, serum ferritin, white blood cell count and differential, &latelet count, and testing for blood in stool. An er%thro&oietic agent should be given to the &redial%sis &atient with CKD and anemia. (arget Ggb levels in the range of :: to :6 g5dL in &redial%sis &atients with CKD. Above such levels have been associated with adverse cardiovascular outcomes. (he er%thro&oietin dose should be a&&ro'imatel% 83 to :33 95kg given two to three doses &er week. K5D@+I guidelines suggest administering iron to maintain the &ercent transferrin saturation 2 63 &ercent, and the serum ferritin level to be greater than :33 ng5mL P16PA1A)I.4 2.1 A4D I4I)IA)I.4 .2 164A9 16P9AC6(64) )H61AP: It is im&ortant to identif% &atients who ma% eventuall% re*uire renal re&lacement thera&% since ade*uate &re&aration can decrease morbidit% and &erha&s mortalit%. -arl% identification enables dial%sis to be initiated at the o&timal time with a functioning chronic access and ma% also &ermit the recruitment and evaluation of famil% members for the &lacement of a renal allograft &rior to the need for dial%sis. In addition, the abilit% of the individual to &s%chologicall% acce&t the re*uirement of life;long renal re&lacement thera&% is often diminished if inade*uate time has ela&sed between the time of recognition of end;stage renal disease and the initiation of dial%sis. !eferral to ne"hrologists Catients with CKD should be referred to a ne&hrologist earl% in the course of their disease, &referabl% before the &lasma creatinine concentration e'ceeds :.6 !:37 micromol5L$ and :.8 mg5dL !:44 17

micromol5L$ in women and men, res&ectivel%, or the e)#" is less than 73 mL5min &er :.I4 m6. (hese subs&ecialists are trained to hel& counsel the &atient in choosing the o&timal renal re&lacement thera&% and to manage the man% issues associated with chronic kidne% disease. Lower costs and5or decreased morbidit% and mortalit% ma% be associated with earl% referral and care b% subs&ecialists. Choice of renal re"lacement thera"y @nce it is determined that renal re&lacement thera&% will eventuall% be re*uired, the &atient should be counseled to consider the advantages and disadvantages of hemodial%sis !in; center or at home$, &eritoneal dial%sis !continuous or intermittent modalities$, and renal trans&lantation !living or deceased donor$. (he 6337 K5D@+I guidelines recommend that &atients with a G&! less than *+ m,/min "er -./* m0 should $e educated concerning these issues . Kidne% trans&lantation is the treatment of choice for end;stage renal disease. A successful kidne% trans&lant im&roves the *ualit% of life and reduces the mortalit% risk for most &atients, when com&ared with maintenance dial%sis. Indications for renal re"lacement thera"y (he decision to initiate dial%sis in a &atient with chronic kidne% disease involves the consideration of subjective and objective &arameters b% the &h%sician and the &atient. (here are a number of clinical indications to initiate dial%sis in &atients with CKD. (hese include : - Cericarditis or &leuritis !urgent indication$. - Crogressive uremic ence&halo&ath% or neuro&ath%, with signs such as confusion, asteri'is, m%oclonus, wrist or foot dro&, or, in severe, cases, sei,ures !urgent indication$. - A clinicall% significant bleeding diathesis attributable to uremia !urgent indication$. - #luid overload refractor% to diuretics. - G%&ertension &oorl% res&onsive to antih%&ertensive medications. - Cersistent metabolic disturbances that are refractor% to medical thera&%. (hese include h%&erkalemia, metabolic acidosis, h%&ercalcemia, h%&ocalcemia, and h%&er&hos&hatemia. - Cersistent nausea and vomiting, weight loss or signs of malnutrition. Gowever, these indications are &otentiall% life;threatening. (he% occur when the &atient has ver% advanced chronic kidne% disease, such as ma% be observed in those who &resent with severe uremia and have not had &rior medical contact. #or &atients under medical care, dela%ing initiation of dial%sis until one or more of these com&lications is &resent ma% &ut the &atient at unnecessar% jeo&ard%N dial%sis should therefore be initiated well before these indications have develo&ed. Catients with chronic kidne% disease should therefore be closel% followed and the )#" estimated. 18

A number of characteristics have therefore been &ro&osed as &ossible indications for earl% institution of maintenance dial%sis: (he 6337 .ational Kidne% #oundation Dial%sis @utcomes +ualit% Initiative !K5D@+I$ for &eritoneal dial%sis and hemodial%sis ade*uac% &ublished guidelines concerning the initiation of dial%sis among &atients with advanced chronic kidne% disease. (he work grou& suggested that the benefits and risks of initiating renal re&lacement thera&% should be considered in &atients with a )#" of less than :8 mL5min &er :.I4 m6 !stage 8 CKD$. Initiation of dial%sis &rior to stage 8 chronic kidne% disease ma% also be re*uired in &atients with certain characteristics and5or com&lications, such as declining health due to the loss of kidne% function.

-. (odule )as7s :. a woman, 64 %o, got diarrhea for three da%s, fre*uenc% more than ten times a week, and vomitting. Dhe admitted hos&ital with decrease of consciousnes. /lood &ressure was H3503 mmGg, &ulse rate :63 '5min, cold acral. 9rine collection for 7 hours was 83 ml. Creatinine serum 6,8 mg5dl. a. what is &roblem list of the &atient R b. is &atient has renal failure R acute or chronicR c. Gow is management of the &atient R 19

6. a male, 88 %o, 83 kg bw, has long standing of h%&ertension. Ge also com&laint of &ain in the right flank area. Ge look &ale. /lood &ressure is :135:33 mgGg. Gemoglobin serum level H mg5dl. Creatinin serum 64 mg5dl, kalium I me*5L. 9rinal%sis reveal albuminuria S4, man% er%throc%te sediment. 9D) show h%drone&hrosis ren e'tra, small stones in lower &ole. "en de'tra contracted. a. b. c. d. e. f. what is &roblem list of the &atient R calculate )#" of the &atient R does &atient has acute or chronic renal failure R what is &robable the cause of renal failureR Does the &atient will be recover% if the causes is correctedR Do &lanning to treat &atients &roblem

20