CHRONIC KIDNEY DISEASE

CHRONIC KIDNEY DISEASE

Tunggul Adi P.Lab Farmasi Klinik, FKIK, UNSOEDEpidemiologi dan EtiologiDuring the two decades spanning 1980 to 2000, the number of patients entering stage 5 (and requiring renal replacement therapy) increased by 5% to 10% per year. However, beginning in 2003 and continuing to the present, the rate of increase has declined to less than 1%. The main factor attributed to this decline has been the implementation of angiotensin-converting enzyme inhibitor (ACEI) and angiotensin receptor blocker (ARB) therapy as a standard of care for those with early stage CKD. DEFINITIONThe National Kidney Foundation (NKF) defines chronic kidney disease as kidney damage or a GFR of less than 60 ml/minute/1.73m2 body surface area for 3 months or moreThis rate corresponds with a serum creatinine concentration higher than 1.5 mg/dL in men or 1.3 mg/dL in womenCKD also can be defined by the presence of urinary albumin in an excretion rate higher than 300 mg per 24 hours or in a ratio of more than 200 mg of albumin to 1 g of creatinineDEFINITION

Epidemiologi dan EtiologiA silent epidemic and is a worldwide public health problemThe causes and incidence rates include diabetic nephropathy (150 cases/million), hypertensive nephropathy (80 cases/million), glomerulonephritis (22 cases/million), and polycystic kidney disease (5 cases/million)DIABETESEstimated numbers of people with diabetes

Epidemiologi dan Etiologi

Risk FactorsBecause the development of CKD is a complex phenomenon, the Kidney Disease Outcomes Quality Initiative (K/DOQI) has recommended categorizing risk factors associated with CKD susceptibility, initiation, and progression factors.

PatofisiologiThe key elements of nephropaties pathway are: (a) loss of nephron mass; (b) glomerular capillary hypertension; and (c) proteinuriaPathophysiology of CRFProgressive destruction of nephrons leads to: Decreased glomerular filtration, tubular reabsorption & renal hormone regulation Remaining functional nephrons compensate Functional and structural changes occurInflammatory response triggeredHealthy glomeruli so overburdened they become stiff, sclerotic and necrotic

Lippincott Williams & Wilkins (2005). Pathophysiology A 2-1 reference for nurses (1st ed.) Ambler, Pa.:Lippincott Williams & Wilkins11Functional Changes of CRFThe Kidneys are unable to:Regulate fluids and electrolytesBalance fluid volume and renin-angiotensin systemControl blood pressureEliminate nitrogen and other wastesSynthesize erythropoietinRegulate serum phosphate and calcium levels12Structural Changes of CRFEpithelial damageGlomerular and parietal basement membrane damageVessel wall thickeningVessel lumen narrowing leading to stenosis of arteries and capillariesSclerosis of membranes, glomeruli and tubulesReduced glomerular filtration rateNephron destruction

Healthy GlomerulusDamaged GlomerulusValerie Kolmer 200613PatofisiologiThe exposure to any of the initiation risk factors can result in loss of nephron mass. the remaining nephrons hypertrophy to compensate for the loss of renal function and nephron mass. Initially, this compensatory hypertrophy may be adaptive. Over time, the hypertrophy can lead to the development of intraglomerular hypertension, possibly mediated by angiotensin II. Angiotensin II is a potent vasoconstrictor of both the afferent and efferent arterioles, but preferentially affects the efferent arterioles, leading to increased pressure within the glomerular capillaries and consequent increased filtration fraction. The development of intraglomerular hypertension usually correlates with the development of systemic arterial hypertension. Animal studies have demonstrated that high intraglomerular capillary pressure impairs the size-selective function of the glomerular permeability barrier, resulting in increased urinary excretion of albumin and frank proteinuria. PatofisiologiProteinuria alone may promote progressive loss of nephrons as a result of direct cellular damage. Filtered proteins such as albumin, transferrin, complement factors, immunoglobulins, cytokines, and angiotensin II are toxic to kidney tubular cells. Numerous studies have demonstrated that the presence of these proteins in the renal tubule activates tubular cells which leads to the upregulated production of inflammatory and vasoactive cytokines, such as endothelin, monocyte chemoattractant protein (MCP-1), and RANTES (regulated upon activation, normal T-cell expressed and secreted). Proteinuria is also associated with the activation of complement components on the apical membrane of proximal tubules. Accumulating evidence now suggests that intratubular complement activation may be the key mechanism of damage in the progressive proteinuric nephropathies. These events ultimately lead to scarring of the interstitium, progressive loss of structural nephron units, and reduction in GFR.Stages of CKDCKD is classified into five stages based on the presence of kidney structural damage (e.g., proteinuria) and/or kidney function (glomerular filtration rate), Stage 1 is indicative of mild structural changes with normal kidney function while Stage 5 is analogous to end stage renal disease for which dialysis or kidney transplantation may be necessaryStages of CKD

Denitions of Abnormalities in Albumin Excretion

Clinical Practice Guidelines for the Detection, Evaluation and Management of CKD

Calculated GFR

Clinical Presentation

Clinical Presentation

SIGNS & SYMPTOMS Lab Value Cues

Anemias - d/t decreased erythropoietin secretion & uremic toxin damage to RBCsAzotemia (elevated nitrogen) d/t retention of nitrogenous wastesCreatinine a component of muscle & its non-protein waste product. Normally filtered in the glomerulus & lost in the urine. Glomerular damage increases reabsorption into the blood. Serum creatinine 3 x normal shows a 75% loss of renal function.

http://office.microsoft.com/en-us/tou.aspx23 SIGNS & SYMPTOMS Lab Value CuesHypocalcemia impaired regulation of Vitamin D leads to decreased absorption & low calcium levels. High phosphorus levels also cause low serum calcium levels.Hyperkalemia impaired excretion of potassium by the kidneys leads to elevated potassium levels.

Hyperlipidemia decreased serum albumin leads to increased synthesis of LDLs & cholesterol by the liver, contributing to elevated lipid levelsProteinuria increased protein filtration d/t glomeruli damage

http://office.microsoft.com/en-us/tou.aspx24 SIGNS & SYMPTOMSVisual / Verbal Cues

Dry mouth, fatigue, nausea d/t hyponatremia & uremiaHypertension d/t sodium & water retentionHypervolemia d/t sodium & water retentionGray/yellow skin d/t accumulated urine pigments

Cardiac irritability d/t hyperkalemiaMuscle cramps d/t hypocalcemiaBone & muscle pain d/t hypocalcemia / hyperphosphatemia Restless leg syndrome d/t toxins effects on the nervous system

http://office.microsoft.com/en-us/tou.aspx25Signs & Symptoms at a Glance

26Importance of Proteinuria in CKD

TREATMENTGoal of TherapyThe goal of therapy is to delay the progression of CKD, thereby minimizing the development or severity of associated complications including cardiovascular disease.Usually the patient with CKD will benefit from modest dietary protein restriction (as a nondrug therapy) as well as pharmacologic therapy. The pharmacologic therapys main purpose is to control the underlying conditions, such as diabetes mellitus and hypertension, that have precipitated the kidney damage so as to prevent further declines in function. Therapy with ACEIs and/or ARBs is a key therapeutic component for almost all patients.Farmakologi-Diabetic CKDThe goals of therapy include an A1c of 200 mg/g for >3 months defines CKD

Clue to the type (diagnosis) of CKDSpot urine total protein-to-creatinine ratio >500-1000 mg/g suggests diabetic kidney disease, glomerular diseases, or transplant glomerulopathy.

Risk factor for adverse outcomesHigher proteinuria predicts faster progression of kidney disease and increased risk of CVD.

Effect modifier for interventionsStrict blood pressure control and ACE inhibitors are more effective in slowing kidney disease progression in patients with higher baseline proteinuria.

Hypothesized surrogate outcomes and target for interventionsIf validated, then lowering proteinuria would be a goal of therapy.