OTHER ASPECTS OF CKD MANAGEMENT CO-MANAGEMENT OF CKD. Module 4 Course Notes. Supported and certifi ed by:

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1 CO-MANAGEMENT OF CKD Module 4 Course Notes OTHER ASPECTS OF CKD MANAGEMENT Supported and certifi ed by: MALAYSIAN SOCIETY OF NEPHROLOGY Malaysian Family Medicine Specialist Association

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3 Table of Contents CONTENTS PAGE 1.0 Acute Kidney Injury Definition Staging Epidemiology Causes Presentation Management End-Stage Renal Disease (ESRD) Renal Replacement Therapy (RRT) Hemodialysis Peritoneal dialysis Renal transplantation Post-transplantation management 11

4 OTHER ASPECTS OF CKD MANAGEMENT 1.0 Acute Kidney Injury Acute kidney injury (AKI) has now replaced the term acute renal failure and a universal defi nition and staging system has been proposed to allow earlier detection and management of AKI. The new terminology enables healthcare professionals to consider the disease as a spectrum of injury. This spectrum extends from less severe forms of injury to more advanced injury when renal replacement therapy (RRT) may be required. Clinically, AKI is characterized by a rapid reduction in kidney function (over hours to weeks) resulting in a failure to maintain fl uid, electrolyte and acid-base homeostasis Definition There have been many attempts to defi ne AKI by international bodies. To this effect the fi rst body established was the Acute Dialysis Quality Initiative (ADQI). It was comprised of international experts representing nephrology and intensive care societies. This group created the Risk, Injury, Failure, Loss, and End-stage Kidney (RIFLE) defi nition and staging system for AKI 2 : Risk: serum creatinine increased 1.5 times or urine production of <0.5 ml/kg for 6 hours Injury: doubling of creatinine or urine production <0.5 ml/kg for 12 hours Failure: tripling of creatinine or creatinine >355 μmol/l (with a rise of >44) (>4 mg/dl) OR urine output below 0.3 ml/kg for 24 hours Loss: persistent AKI or complete loss of kidney function for more than 4 weeks End-stage renal disease: complete loss of kidney function for more than 3 months Shortly after this the Acute Kidney Injury Network (AKIN) was formed. The AKIN group modifi ed the RIFLE staging system to refl ect the clinical signifi cance of relatively small rises in serum creatinine. 3,4 Most recently another group, the international guideline group, Kidney Disease: Improving Global Outcomes (KDIGO) has brought together international experts from many different specialties to produce a defi nition and staging system that harmonizes the previous defi nitions and staging systems proposed by both ADQI and AKIN. 5 The KDIGO defi nes AKI by the following criteria: Serum creatinine rises by 26 μmol/l within 48 hours or Serum creatinine rises 1.5 fold from the reference value, which is known or presumed to have occurred within one week or urine output is < 0.5 ml/kg/hr for >6 consecutive hours. The reference serum creatinine should be the lowest creatinine value recorded within 3 months of the event. If a reference serum creatinine value is not available within 3 months and AKI is suspected repeat serum creatinine within 24 hours a reference serum creatinine value can be estimated from the nadir serum creatinine value if patient recovers from the AKI. 4

5 1.2 Staging The staging of AKI as per KDIGO is as follows 5 : Stage Serum creatinine (SCr) criteria Urine output criteria 1 increase 26 μmol/l within 48hr or increase 1.5 to 1.9 X reference SCr <0.5 ml/kg/hr for > 6 consecutive hr 2 increase 2 to 2.9 X reference SCr <0.5 ml/kg/hr for > 12 hr 3 increase 3 X reference SCr or increase 354 μmol/l or commenced on renal replacement therapy (RRT) irrespective of stage <0.3 ml/kg/hr for > 24 hrs or anuria for 12 hr 1.3 Epidemiology The reported prevalence of AKI from US data ranges from 1% (community-acquired) up to 7.1% (hospital-acquired) of all hospital admissions. 6,7 The incidence of AKI requiring RRT ranges from 22 per million population (pmp)/year 2 to 203 pmp/year. 8 AKI is common in hospitalized patients and has a poor prognosis with the mortality ranging from 10%-80% dependent upon the patient population studied. An estimated 5 20% of critically ill patients experience an episode of AKI during the course of their illness and AKI receiving RRT has been reported in 4 9% of all admissions to intensive-care units (ICU). 9 Data from the Intensive Care National Audit Research Centre (ICNARC) suggests that AKI accounts for nearly 10 percent of all ICU bed days. 10 In a study by Ostermann et al, ICU mortality was 10.7% in patients without AKI, 20.1% in those with AKI I, 25.9% in those with AKI II, and 49.6% in those with AKI III. Intensive care unit mortality rises with the increasing number of associated failed organs and preexisting chronic health problems. 11 Studies show AKI to be a risk factor for death when combined with other comorbidities. AKI has been shown to be strongly associated with 30-day mortality after acute right-side heart failure hospitalization (odds ratio 5.3, 95% CI ). 12 Liangos et al found in a study with a great number of inpatients that chronic diseases such as diabetes mellitus (DM), high blood pressure (HBP), coronary artery disease, congestive heart failure, neoplasms and HIV infection were associated with a higher risk of developing AKI and consequently a higher mortality. 13 In contrast, other studies suggest AKI mortality is not associated with preexisting chronic diseases, such as HBP, DM or chronic obstructive pulmonary disease (COPD), but rather with clinical events over the hospitalization, such as dialysis requirement, oliguria and one or more organ failure. 14 5

6 OTHER ASPECTS OF CKD MANAGEMENT 1.4 Causes of AKI Prerenal: a. Volume depletion (e.g. hemorrhage, severe vomiting or diarrhea, burns, inappropriate diuresis) b. Edematous states: cardiac failure, cirrhosis, nephrotic syndrome c. Hypotension (e.g. cardiogenic shock, sepsis, anaphylaxis) d. Cardiovascular (e.g. severe cardiac failure, arrhythmias) e. Renal hypoperfusion: non-steroidal anti-infl ammatory drugs (NSAIDs) or selective cyclooxygenase-2 (COX-2) inhibitors, angiotensin-converting enzyme (ACE) inhibitors or angiotensin-ii receptor antagonists, abdominal aortic aneurysm, renal artery stenosis or occlusion, hepatorenal syndrome 2. Intrinsic acute kidney injury (AKI): a. Glomerular disease: glomerulonephritis, thrombosis, hemolytic uremic syndrome b. Tubular injury: acute tubular necrosis (ATN) following prolonged ischemia; nephrotoxins (e.g. aminoglycosides, radiocontrast media, myoglobin, cisplatin, heavy metals, light chains in myeloma kidney) c. Acute interstitial nephritis due to drugs (e.g. NSAIDs), infection or autoimmune diseases d. Vascular disease: vasculitis (usually associated with antineutrophil cytoplasmic antibody), cryoglobulinemia, polyarteritis nodosa, thrombotic microangiopathy, cholesterol emboli, renal artery stenosis, renal vein thrombosis, malignant hypertension e. Eclampsia 3. Postrenal: a. Calculus b. Blood clot c. Papillary necrosis d. Urethral stricture e. Prostatic hypertrophy or malignancy f. Bladder tumor g. Radiation fi brosis h. Pelvic malignancy i. Retroperitoneal fi brosis 1.5 Presentation 15 The presentation will depend on the underlying cause and severity of AKI. There may be no symptoms or signs, but oliguria (urine volume less than 400 ml/24 hours) is common. There is an accumulation of fl uid and nitrogenous waste products demonstrated by a rise in blood urea and creatinine. 6

7 Symptoms Urine output: AKI is usually accompanied by oliguria or anuria, but polyuria may occur. Abrupt anuria suggests an acute obstruction, acute and severe glomerulonephritis, or acute renal artery occlusion. Gradual diminution of urine output may indicate a urethral stricture or bladder outlet obstruction, e.g. benign prostatic hyperplasia. Nausea, vomiting Diffi culty in breathing Confusion Signs Hypertension Abdomen: may reveal a large, painless bladder typical of chronic urinary retention Fluid overload with raised jugular venous pressure (JVP), pulmonary edema and peripheral edema Pericardial rub 1.6 Management 15 Principles of management of acute kidney injury (AKI) Advice from a nephrologist should be sought for all cases of AKI, as early consultation can improve outcomes. Identify and correct the etiology. Optimize cardiac output and renal blood fl ow. Review drugs: stop nephrotoxic agents; adjust doses and monitor concentrations where appropriate. Accurately monitor fl uid balance and daily body weight. Identify and treat acute complications (hyperkalemia, acidosis, pulmonary edema). Optimize nutritional support: adequate calories, minimal nitrogenous waste production, potassium restriction. Identify and aggressively treat infection; minimize indwelling lines; remove bladder catheter if anuric. Identify and treat bleeding tendency. Prophylaxis with proton pump inhibitor (PPI) or H2-receptor antagonist (H2RA), transfuse if required, avoid aspirin. Initiate dialysis before uremic complications emerge. 7

8 OTHER ASPECTS OF CKD MANAGEMENT 2.0 End-Stage Renal Disease (ESRD) ESRD is the complete, or almost complete failure of the kidneys to function. It usually follows CKD. A person may have gradual worsening of kidney function for years or more before progressing to ESRD. Conditions that may lead to ESRD include hypertension and diabetes mellitus. Data from the Malaysian Dialysis and Transplant Registry indicate that the dialysis prevalence rate more than doubled over the last 10 years, from 325 per million population in 2001 to more than 800 per million in The table below shows the renal replacement therapy (RRT) prevalence rates in Malaysia from 2001 to RRT prevalence rate in Malaysia per million population Prevalence rate Dialysis Transplant Renal Replacement Therapy (RRT) When a patient developed ESRD, he/she needs renal replacement therapy to support his/her life. Renal replacement therapy includes: 1. Hemodialysis 2. Peritoneal dialysis 3. Renal transplantation Hemodialysis 17 In hemodialysis, a patient s blood is pumped into a dialyzer containing 2 fl uid compartments confi gured as bundles of hollow fi ber capillary tubes or as parallel, sandwiched sheets of semipermeable membranes. In either confi guration, blood in the fi rst compartment is pumped along one side of a semipermeable membrane while a crystalloid solution (dialysate) is pumped along the other side, in a separate compartment, in the opposite direction. Concentration gradients of solute between blood and dialysate lead to desired changes in the patient s serum solutes, such as a reduction in urea nitrogen and creatinine; an increase in bicarbonate and equilibration of Na, Cl, K and Mg. The dialysate compartment is under negative pressure relative to the blood compartment to prevent fi ltration of dialysate into the bloodstream and to remove the excess fl uid from the patient. The dialyzed blood is then returned to the patient. The patient is usually systemically anticoagulated during hemodialysis to prevent blood from clotting in the dialysis machine. 8

9 The immediate objectives of hemodialysis are to correct electrolyte and fl uid imbalances and remove toxins. Longer-term objectives in patients with renal failure are to: Optimize the patient s functional status, comfort and BP Prevent uremia and its complications Improve survival The optimal dose of hemodialysis is uncertain, but most patients do well with 3 to 5 hours of hemodialysis 3 times/wk. One way to assess the adequacy of each session is by measuring BUN before and after each session. A 65% decrease of BUN from predialysis level ([predialysis BUN postdialysis BUN]/predialysis BUN 100% is 65%) indicates an adequate session. Specialists may use other, more calculation-intensive formulas, such as KT/V 1.2 (where K is the urea clearance of the dialyzer in ml/min, T is dialysis time in minutes, and V is volume of distribution of urea [total body water] in ml). Hemodialysis is usually done through a surgically created arteriovenous fi stula. However, dialysis can be done through a central vein catheter if an arteriovenous fi stula has not yet been created or is not ready for use or if creation of an arteriovenous fi stula is impossible. Overall adjusted annual mortality in hemodialysis-dependent patients tends to be about 20%. The 5-year survival rate is lower for patients with diabetes than for patients with glomerulonephritis. Death is generally mostly attributable to cardiovascular disease, followed by infection and withdrawal from hemodialysis Peritoneal Dialysis (PD) PD was the modality fi rst used for treatment of AKI. 18 Intermittent PD was widely used in the 1970s due to its various advantages. Later, continuous PD therapies became available through automated cycling machines (cyclers). In western countries, PD is not commonly used in dialytic management of AKI due to the availability of newer HD techniques and development of continuous renal replacement therapies (CRRTs). 19 Currently, PD is being used primarily in the treatment of ESRD. In PD, solute and fl uid exchange occur between peritoneal capillary blood and dialysis solution in the peritoneal cavity. There are few modalities of PD in the treatment of ESRD: 1. Continuous ambulatory PD 2. Night intermittent PD 3. Continuous cycling PD 9

10 OTHER ASPECTS OF CKD MANAGEMENT Contraindications to PD 19 : Recent abdominal surgery Pleuroperitoneal communication Diaphragmatic severe respiratory failure Life-threatening hyperkalemia not responding to medical therapy Extremely hypercatabolic state Severe volume overload in a patient not on a ventilator Severe gastroesophageal refl ux disease Low peritoneal clearance Fecal or fungal peritonitis Abdominal wall cellulitis AKI in pregnancy Renal Transplantation Renal transplantation offers the best chance of long-term survival in patients with ESRD. It can restore normal kidney function and correct all metabolic abnormalities of CKD. All patients should be considered for transplantation unless there are active contraindications. 20 Absolute contraindications to transplantation 20 : Active malignancy (at least 2 years of complete remission is recommended for most tumors prior to transplantation) Active vasculitis or anti glomerular basement membrane (anti-gbm) antibody disease (at least 1 year of remission is recommended prior to transplantation) Severe ischemic heart disease Severe occlusive aorto-iliac vascular disease Relative contraindications to transplantation 20 : Age (either very young or very old) High risk of disease recurrence in the transplant kidney Signifi cant comorbidity Kidney grafts may be obtained from either a cadaver or from a living donor. Immunological factors strongly infl uence the matching of a donor to a specifi c recipient as graft rejection is a major cause of transplant failure. The degree of matching for major histocompatibility (MHC) antigens, particularly HLA-DR, infl uences the incidence of rejection. 20 In Malaysia, overall patient survival rates from 2001 to 2010 have been 94%, 91%, 87% and 80% at year 1, 3, 5 and 10 respectively

11 Post-transplantation management Immunosuppressive therapy is required throughout the life of the transplant to prevent rejection. This is associated with an increased incidence of infections (eg cytomegalovirus or Pneumocystis jirovecii), and an increased risk of malignancies, especially of the skin. 20 Common immunosuppressive agents used in Malaysia include cyclosporin, tacrolimus and mycophenolate mofetil. These agents are usually used in combination with other drugs such as prednisolone. 16 References: 1. Lewington A, Kanagasundram S. Clinical practice guidelines acute kidney injury. Renal Association (April 2008). Available at AcuteKidneyInjury.aspx. Accessed August 24th, Bellomo R, etal. Crit Care 2004;8:R204-R Mehta RL, et al. Crit Care 2007;11:R Molitoris BA, et al. Nat Clin Pract Nephrol 2007;3(8): Kidney Disease: Improving Global Outcomes. Clinical practice guideline on acute kidney injury available at htt://www/kdigo.org accessed on 17th August Nash K, et al. Am J Kidney Dis 2002; 39: Kaufman J, et al.. Am J Kidney Dis 1991; 17: Steven D, et al. Semin Resp Crit Care Med 2006;27: Metnitz PGH, et al. Crit Care Med 2002; 30: Intensive-Care National Audit Research Centre 2005 available at accessed on 15 Aug Ostermann M, et al. J Crit Care 2011 Jul 26. [Epub ahead of print] 12. Haddad F, et al. J Card Fail 2011;17(7): Liangos O, et al. Clin J Am SocNephrol 2006;1: Bucuvic et al. Rev Assoc Med Bras 2011;57(2): Acute Kidney Injury. Available at Accessed August 24th, th report of the Malaysian Dialysis and Transplant Registry Available at Accessed August 29th, Renal Replacement therapy. Available at Accessed August 24th, Maxwell MHR, et al. JAMA 1959;170(8): Ansari N. Int J Nephrol 2011;2011: Epub 2011 Jun Innes JA, ed. Davidson s Essentials of Medicine. Churcill Livingston Elsevier;2009:

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