Chronic kidney disease

Chitranon Chan-on, MDExcellence center for kidney transplantation, KKU

I love u all of my kidney

Outline

• Introduction

• Definition and diagnosis

• Staging

• Symptomatology

• Epidemiology

• Management

• Renal replacement therapy modality

Introduction • toxic waste removal

• water and salt regulation

• BP controlling

• body's pH balancing

• Hormone producing: EPO, vitamin D

azotemia and uremia.

fluid overload

acidosis and hypertension

electrolyte imbalance anemia, renal osteodystrophy,extraskeletal calcification.

Impact

Cardiovascular (CV) disease as a 3 stage continuum

Stage 1. stage2. stage 3.

US data

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

Cause of ESRD

• DN is the most common cause of ESRD

• DN-CKD has higher mortality than non-DN-CKD

Definition and diagnosis

CKD definitionCriteria 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

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: 1–150.

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).

Staging

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: 1–150.

CGA

CKD definition & criteria update 2012

Pathophysiology

CKD

Non-diabetic KD

Glomerular disease

Tubulointerstitial disease

Vascular disease

Cystic disease

Diabetic KD

Type 1 DM

Type 2 DM

Disease in kidney transplant

Simplified Classification of CKD by diagnosis

Simplified Classification of CKD by diagnosis

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

Increased pressure and flow sclerosis and dropout of the remaining nephrons

Intrarenal activity of the RAAS axis TGF-beta

Risk factors

• Age

• Diabetes*

• Hypertension*

• FH of renal disease

• Renal transplant

Risk Factors for CKD

Initiation factors

Diabetes* Hypertension* Autoimmune diseases Primary GN Systemic infections Nephrotoxic agents

Progression factors

CKD

• Persistent activity of underlying disease

• Persistent proteinuria

• Elevated blood pressure*

• Elevated blood glucose*

• High protein/phosphate diet

• Hyperlipidemia

• Hyperphosphatemia

• Anemia

• Cardiovascular disease

• Smoking

Progression factors

Clinical manifestation in CKD

Fluid & electrolyte disturbances

•Volume expansion

•Hyponatremia

•Hyperkalemia •Hyperphosphatemia

Endocrine-metabolic disturbance

• Carbohydrate resistance • Hyperuricemia

Metabolic bone disease • Secondary hyperparathyroidism

• Adynamic bone/ osteodystrophy

• Vitamin D–deficient osteomalacia

• Infertility and sexual dysfunction

• Amenorrhea

Dyslipidemia• Hypertriglyceridemia

• Increased apolipoprotein A level

• Decreased high-density lipoprotein level

• 2-Microglobulin associated amyloidosis

Metabolic disturbances

Vitamin D deficiency & Phosphate retention

CKD

Phosphate RetentionVitamin D Deficiency

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

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

highest cardiovascular 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.

Neuromuscular disturbances• Fatigue

• Sleep disorders

• Headache

• Impaired mentation

• Lethargy

• Asterixis

• Muscular irritability

• Peripheral neuropathy

• Restless legs syndrome

• Myoclonus

• Seizures

• Coma

• Muscle cramps• Myopathy

Cardiovascular and pulmonary disturbances

• Arterial hypertension

• Pericarditis

• Uremic lung

• Hypertrophic or dilated cardiomyopathy

• Congestive heart failure or pulmonary edema

• Accelerated atherosclerosis • Vascular calcification

CKD contribute to Cardiovascular mortality

Cardiovascular (CV) disease as a 3 stage continuum

Stage 1. stage2. stage 3.

Dermatologic disturbances• Pallor

• Hyperpigmentation

• Pruritus

• Ecchymoses

• Nephrogenic fibrosingdermopathy

• Uremic frost

Gastrointestinal disturbances

• Anorexia

• Nausea and vomiting

• Gastroenteritis

• Peptic ulcer

• Gastrointestinal bleeding

• Idiopathic ascites

Hematologic and immunologic disturbances

• Anemia

• Bleeding diathesis

• Increased susceptibility to infection

• Leukopenia

• Lymphocytopenia

• Thrombocytopenia

Management

Natural progression

Screening and risk reduction

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.

Screening procedure for pts at increased CKD risk

Keep weight in check. Exercise regularly. Limit salt intake. Stop smoking. Limit intake of alcohol

CVD risk in CKD evaluation & reduction

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.

Control progression factors

3 interventions have been proved to slow the CKD progression:

@ BP control@ glycemic control in diabetes pts @ 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.

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.

Glycemic control

the Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan(RENAAL) study

ARB-ACEI therapy

ACEI/ARB

Ang II

Glomerular arteriole

Bradykininall periphery

Renin-Angiotensin System (RAS)

footnoteAdapted from Kim S et al. Pharmacological Reviews. 2000;52:11–34.

Angiotensinogen

Angiotensin I

Angiotensin II

ACE inhibitor

ACE

AT1 antagonist

Signaling cascades

Gene expression

Cardiac diseasesVascular diseasesRenal diseases

AT1 AT2

Renin

?

Bradykinin

Inactive fragmentsAlternativepathways

GFRProteinuriaAldosterone release (BP)

Glomerular sclerosis

Pathological effects of Angiotensin II-AT1

A II AT1

receptor

AtherosclerosisVasoconstriction (BP)Vascular hypertrophyEndothelial dysfunction

LV hypertrophyFibrosisRemodelingApoptosis

Stroke

DEATH

Hypertension

Heart failureMI

Renal failure

“Surrogate end points” (Organ/tissue Changes)

“Outcomes Endpoints”

Angiotensin II receptor blocker

Angiotensin II effect

LOX-1: lectinlike oxLDL receptor-1PAI: Plasminogen activator inhibitor BK: BradykininPGs: ProstaglandinsNO: Nitric oxide tPA: Tissue plasminogen activator

ACEI

-ARB

-

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

2 gm /day orNo Added Salt

Stages and Prevalence of CKD

17.7 %

• Asymptomatic until volume overload/uremia

DM /Gen Med clinic

CKD clinic

•Hemodialysis

CKD V

Pre-dialysis education

CKD from any cause

•Kidney transplantation

•Peritoneal dialysis •Conservative therapy

• Admission with complicated problems AKI

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

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