Chronic kidney disease

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1 Chronic kidney disease I love u all of my kidney Chitranon Chan-on, MD Excellence center for kidney transplantation, KKU

2 Outline Introduction Definition and diagnosis Staging Symptomatology Epidemiology Management Renal replacement therapy modality

3 Introduction azotemia and uremia. fluid overload toxic waste removal water and salt regulation BP controlling body's ph balancing Hormone producing: EPO, vitamin D acidosis and hypertension electrolyte imbalance anemia, renal osteodystrophy, extraskeletal calcification.

4 Impact

5 Cardiovascular (CV) disease as a 3 stage continuum Stage 1. stage2. stage 3.

6 Kidney diseases rank as the 7th largest killer amongst all the diseases prevalent worldwide US data

7 Cause of ESRD DN is the most common cause of ESRD DN-CKD has higher mortality than non-dn-ckd

8 Definition and diagnosis

9 CKD definition Criteria for CKD (either of the following present for > 3 months) 1. Markers of kidney damage Albuminuria (AER >30 mg/24 hours; ACR >30 mg/g [> 3 mg/mmol]) Urine sediment abnormalities Electrolyte and other abnormalities due to tubular disorders Abnormalities detected by histology Structural abnormalities detected by imaging History of kidney transplantation 2. Decreased GFR: egfr < 60 ml/min/1.73 m2

CKD definition & criteria update 2012 CKD is defined as abnormalities of kidney structure or function, present for > 3 months, with implications for health and CKD is classified based on cause, GFR

10 CKD definition & criteria update 2012 CKD is defined as abnormalities of kidney structure or function, present for > 3 months, with implications for health and CKD is classified based on cause, GFR category, and albuminuria category (CGA). Improving Global Outcomes (KDIGO) CKD Work Group. KDIGO 2012 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. Kidney inter., Suppl. 2013; 3:

11 Staging

12 CKD definition & criteria CGA update 2012 Improving Global Outcomes (KDIGO) CKD Work Group. KDIGO 2012 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. Kidney inter., Suppl. 2013; 3:

14 Pathophysiology

15 Simplified Classification of CKD by diagnosis Glomerular disease Nondiabetic KD Tubulointersti tial disease Vascular disease Cystic disease CKD Diabetic KD Type 1 DM Type 2 DM Disease in kidney transplant

16 Simplified Classification of CKD by diagnosis

Initiating mechanisms specific to the underlying

interstitium Intrarenal activity of the RAAS

17 Initiating mechanisms specific to the underlying causes - immune complexes ex.gn, AIN - mediators of inflammation ex. AIN, drugs toxin in the renal tubules and interstitium Intrarenal activity of the RAAS axis TGF-beta Increased pressure and flow sclerosis and dropout of the remaining nephrons

18 Risk Factors for CKD Risk factors Age Diabetes* Hypertension* FH of renal disease Renal transplant Initiation factors Diabetes* Hypertension* Autoimmune diseases Primary GN Systemic infections Nephrotoxic agents Progression factors CKD

19 Progression factors Persistent activity of underlying disease Persistent proteinuria Elevated blood pressure* Elevated blood glucose* High protein/phosphate diet Hyperlipidemia Hyperphosphatemia Anemia Cardiovascular disease Smoking

20 Clinical manifestation in CKD

21 Fluid & electrolyte disturbances Volume expansion Hyponatremia Hyperkalemia Hyperphosphatemia

Metabolic bone disease Endocrine-metabolic

bone/ osteodystrophy Vitamin D deficient

Increased apolipoprotein A level Decreased

associated amyloidosis Carbohydrate resistance

22 Metabolic bone disease Endocrine-metabolic disturbance Secondary hyperparathyroidism Adynamic bone/ osteodystrophy Vitamin D deficient osteomalacia Dyslipidemia Hypertriglyceridemia Increased apolipoprotein A level Decreased high-density lipoprotein level 2-Microglobulin associated amyloidosis Carbohydrate resistance Hyperuricemia Infertility and sexual dysfunction Amenorrhea Metabolic disturbances

Vitamin D deficiency & Phosphate retention CKD Vitamin D

D Low PO diet PO binder -Ca; CaCO3,citrate -non-ca: Sevelamer

hypercalcemia, arterial calcification, adynamic BD,

the diagnosis, evaluation, prevention, and treatment of

23 Vitamin D deficiency & Phosphate retention CKD Vitamin D Deficiency Phosphate Retention Active Vit. D Low PO diet PO binder -Ca; CaCO3,citrate -non-ca: Sevelamer C/I for Ca containing PO binder: persist or recur hypercalcemia, arterial calcification, adynamic BD, persistently low PTH KDIGO clinical practice guideline for the diagnosis, evaluation, prevention, and treatment of chronic kidney disease mineral and bone disorder (CKD MBD). Kidney International 2009; 76 (Suppl 113): S1 S130

vascular/valvular calcification National Kidney Foundation.

24 highest cardiovascular risk In pts with CKD stages 3 5D: * lateral abdominal plain film /CT based imaging detect vascular calcification Echocardiogram for valvular calcification if +ve for vascular/valvular calcification National Kidney Foundation. K/DOQI Clinical Practice Guidelines for Chronic Kidney Disease: Evaluation, Classification and Stratification. Am J Kidney Dis 39:S1-S266, 2002 (suppl 1) S1-S266.

25 Neuromuscular disturbances Fatigue Sleep disorders Headache Impaired mentation Lethargy Asterixis Muscular irritability Peripheral neuropathy Restless legs syndrome Myoclonus Seizures Coma Muscle cramps Myopathy

26 Cardiovascular and pulmonary disturbances Arterial hypertension Pericarditis Uremic lung Hypertrophic or dilated cardiomyopathy Congestive heart failure or pulmonary edema Accelerated atherosclerosis Vascular calcification

27 CKD contribute to Cardiovascular mortality

28 Cardiovascular (CV) disease as a 3 stage continuum Stage 1. stage2. stage 3.

29 Dermatologic disturbances Pallor Hyperpigmentation Pruritus Ecchymoses Nephrogenic fibrosing dermopathy Uremic frost

30 Gastrointestinal disturbances Anorexia Nausea and vomiting Gastroenteritis Peptic ulcer Gastrointestinal bleeding Idiopathic ascites

31 Hematologic and immunologic disturbances Anemia Bleeding diathesis Increased susceptibility to infection Leukopenia Lymphocytopenia Thrombocytopenia

32 Management

33 Natural progression

34 Screening and risk reduction

35 Screening procedure for pts at increased CKD risk National Kidney Foundation. K/DOQI Clinical Practice Guidelines for Chronic Kidney Disease: Evaluation, Classification and Stratification. Am J Kidney Dis 39:S1-S266, 2002 (suppl 1) S1-S266.

36 CVD risk in CKD evaluation & reduction Keep weight in check. Exercise regularly. Limit salt intake. Stop smoking. Limit intake of alcohol

37 Prevent and correct AKI on top CKD Volume depletion Intravenous radiographic contrast Antimicrobial agents (ex. aminoglycosides and amphob) NSAIDs,including COX 2 inhibitors ACEI & ARB CNI: Cyclosporine and tacrolimus Obstruction of the urinary tract National Kidney Foundation. K/DOQI Clinical Practice Guidelines for Chronic Kidney Disease: Evaluation, Classification and Stratification. Am J Kidney Dis 39:S1-S266, 2002 (suppl 1) S1-S266.

38 Control progression factors 3 interventions have been proved to slow the CKD BP glycemic control in diabetes proteinuria reduction with an ACEI or ARB National Kidney Foundation. K/DOQI Clinical Practice Guidelines for Chronic Kidney Disease: Evaluation, Classification and Stratification. Am J Kidney Dis 39:S1-S266, 2002 (suppl 1) S1-S266.

39 Control progression factors Other may be beneficial for slow progression of CKD lipid-lowering therapy partial correction of anemia dietary protein restriction smoking National Kidney Foundation. K/DOQI Clinical Practice Guidelines for Chronic Kidney Disease: Evaluation, Classification and Stratification. Am J Kidney Dis 39:S1-S266, 2002 (suppl 1) S1-S266.

40 Glycemic control

41 ARB-ACEI therapy the Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan (RENAAL) study

42 Glomerular arteriole Bradykinin all periphery ACEI/ ARB Ang II

fragments Signaling cascades Gene expression? footnote Adapted from Kim S et al.

43 Renin-Angiotensin System (RAS) Angiotensinogen Alternative pathways AT 1 antagonist Renin Angiotensin I ACE Angiotensin II AT 1 AT 2 ACE inhibitor Bradykinin Inactive fragments Signaling cascades Gene expression? footnote Adapted from Kim S et al. Pharmacological Reviews. 2000;52: Cardiac diseases Vascular diseases Renal diseases

44 Pathological effects of Angiotensin II-AT 1 Surrogate end points (Organ/tissue Changes) Outcomes Endpoints Atherosclerosis Vasoconstriction (BP) Vascular hypertrophy Endothelial dysfunction Stroke Hypertension A II AT 1 receptor LV hypertrophy Fibrosis Remodeling Apoptosis Heart failure MI DEATH Angiotensin II receptor blocker GFR Proteinuria Aldosterone release (BP) Glomerular sclerosis Renal failure

45 Angiotensin II effect ACEI - ARB - LOX-1: lectinlike oxldl receptor-1 PAI: Plasminogen activator inhibitor BK: Bradykinin PGs: Prostaglandins NO: Nitric oxide tpa: Tissue plasminogen activator

46 2 gm /day or No Added Salt dietary protein restriction: intake to 0.60 to 0.75 g/kg/day in patients with a GFR < 25 ml/min/1.73 m2.33

47 Stages and Prevalence of CKD

48 17.7 %

with complicated problems AKI Peritoneal dialysis CKD V

49 CKD from any cause Asymptomatic until volume overload/uremia DM /Gen Med clinic CKD clinic Admission with complicated problems AKI Peritoneal dialysis CKD V Pre-dialysis education Conservative therapy Hemodialysis Kidney transplantation

50 Take home massages CKD: common disease and recognized as public health problem worldwide CKD: major complication of common disease DM/HTN Any renal injury: residual damaged renal tissue CKD Life style modification + pharmacotherapy

Acute renal failure ARF

Acute renal failure ARF Definition ARF is a clinical syndrome characterized by an abrupt decline in GFR and the accumulation of nitrogenous waste (BUN & creatinine). The decrease in GFR occurs relatively