Chronic Kidney Disease

MOHAMAD S. RABABAH , MD Consultant Nephrologist , Head of Renal Unit, KAUH_Jordan

Prevalence

1 in 5 diabetics 1 in 6 hypertensives 1 in 5 of all elderly > 80 without HTN and DM

Definition of CKD
Structural or functional abnormalities of the kidneys for >3 months, as manifested by either:
1. Kidney damage, with or without decreased GFR, as defined by
pathologic abnormalities markers of kidney damage, including abnormalities in the composition of the blood or urine or abnormalities in imaging tests

2. GFR <60 ml/min/1.73 m2, with or without kidney damage

Definition

For greater than 3 months Kidney damage

Abnormal structure by imaging Abnormal function by urine/bloodwork

OR

GFR < 60

Classification of CKD by Diagnosis

Diabetic Kidney Disease Glomerular diseases (autoimmune

hypertension, microangiopathy)

diseases, systemic infections, drugs, neoplasia)

Vascular diseases (renal artery disease, Tubulointerstitial diseases (urinary tract

infection, stones, obstruction, drug toxicity)

Cystic diseases (polycystic kidney disease) Diseases in the transplant (Allograft

nephropathy, drug toxicity, recurrent diseases, transplant glomerulopathy)

Screening

Screen all high risk and age > 55

HTN, DM, recurrent UTI Systemic illness that affects kidney (NNS = 8.7)

Screen with Creatinine to calculate GFR AND urine protein analysis

Glomerular Filtration
You MUST calculate the GFR! Use an equation MDRD or C-G

Use a 24 hr urine in special cases

Prevalence of Abnormalities at each level of GFR

Hypertension* Unable to walk 1/4 mile Serum calcium < 8.5 mg/dL
Proportion of population (%)

Hemoglobin < 12.0 g/dL Serum albumin < 3.5 g/dL Serum phosphorus > 4.5 mg/dL

90 80 70 60 50 40 30 20 10 0 15-29 30-59 60-89 90+

Estimated GFR (ml/min/1.73 m2)

*>140/90 or antihypertensive medication

p-trend < 0.001 for each abnormality

Screening

Screen all high risk and age > 55

HTN, DM, recurrent UTI Systemic illness that affects kidney

Screen with Creatinine to calculate GFR AND urine protein analysis

Proteinuria

Good evidence for screening with annual micro-albumin in DM Consider screening in HTN, age> 55

WHAT to use? - urine microalbumin - urine micro for casts

Proteinuria

Protein in urine is associated with a more rapid decline in renal function This decline can be slowed by ACE-I or ARB even without diabetes Can be helpful in diagnosis if not DM

Causes of CKD

Diabetes

Non-diabetic

Hypertension?? Transplant

Glomerular Tubulointerstitial Vascular Cystic

Non-DM Causes of CKD

Glomerular

Tubulointerstitial

Lupus or vasculitis Hepatitis or HIV Endocarditis Amyloidosis Medications Lithium

Ratio of protein: creatinine is high

Myeloma Pyleonephritis Obstruction BPH Tumor Chronic reflux Sarcoidosis

Non-DM Causes of CKD

Vascular

Hypertension Renal artery stenosis Renal vasculitis Sickle cell HUS

Cystic and other hereditary renal diseases Transplant

Low-flow states

Chronic rejection Medications Chronic disease

Cirrosis, CHF, etc.

CKD and no diabetes?

Medications? Family history? Risks of HIV and Hepatitis Rashes, joints, renal bruit Screen again for diabetes Look at urine micro for clues Consider ESR, SPEP, ANA, ANCA Renal ultrasound

CKD Stages

Stage 1

GFR > 90

Damage but normal or elevated GFR

Stage Stage Stage Stage

2 3 4 5

GFR GFR GFR GFR

60-90 30-60 15-30 < 15

Goals of Care
1.

2.
3.

Slow decline in renal function Prevent cardiovascular disease Detect and manage complications

Anemia Hyperparathyroidism Bone disease Electrolyte abnormalities Vascular complications

Bone Disease in Renal Failure

Normal Bone Remodelling Cycle

Resorption
osteoclasts

Formation
osteoblasts matrix

Quiescence

Mineralisation

Pathogenesis

Kidney failure disrupts systemic calcium and phosphate homeostasis and affects the bone, GIT and parathyroid glands. In kidney failure there is decreased renal excretion of phosphate and diminished production of calcitriol (1,25dihydroxyvitamin D)

The increased phosphate and reduced calcium, feedback and lead to secondary hyperparathyroidism, metabolic bone disease, soft tissue calcifications and other metabolic abnormalities

Calitriol increases serum calcium levels

PO4
GFR 1,25 DHCC
Calcitriol

Ca

PTH

Secondary hyperparathyroidism

In renal failure driven by

Hypocalcaemia Decreased vitamin D hyperphosphataemia

Clinical manifestations of bone disease

Most with CKD and mildly elevated PTH are asymptomatic When present classified as either
1. Musculoskeletal 2. Extra-skeletal

Uraemic Bone Remodelling Cycle

Resorption
osteoclasts

Accelerates:

High PO4 or Low Ca2+, calcitriol, HCO3, oestrogen Via PTH*, IL-1,6 & TNF

Formation
osteoblasts matrix

Quiescence Retards:
Calcitriol*, Age, Diabetes, Al3+, PTHx

Mineralisation
*Acts via osteoblasts

High turn over bone disease

Due to excess PTH Increased bone turnover activity (greater number of osteoclasts and osteoblasts) and defective mineralization. Associated with bone pain and increased risk of fractures. Severe symptomatic disease is currently uncommon with modern therapy.

Osteomalacia

Formally linked to aluminium toxicity

From aluminium based phosphate binders From contamination of water in diasylate solutions

Mixed uraemic bone disease

Mixture of high turn over bone disease and osteomalacia

Adynamic bone disease

Characterized by low osteoblastic activity and bone formation rates Seen in up to 40% HD and 50% PD May be due to excess suppression of the parathyroid gland with therapies, particularly calcium-containing phosphate binders and vitamin D analogues. Typically maintain a low serum intact PTH concentration, which is frequently accompanied by an elevated serum calcium level. Felt to represent a state of relative hypoparathyroidism

To slow decline

Low salt diet (for HTN) Low protein diet in CKD 4 & 5

Nutrition consult!

Avoid nephrotoxic agents

Contrast dye, NSAIDs, gentamicin

To slow decline

Diabetes control HA1c ~ 7.0 7.5

Metformin? Glipizide v. Glyburide

Blood pressure control - < 130/80

ACE-I or ARB Diuretics thiazide for GFR > 30 - furosemide for GFR < 30

To slow decline
Prescribe an ACE-I or ARB for proteinuria + CKD even in the ABSENCE of diabetes

Goals of Care
1.

2.
3.

Slow decline in renal function Prevent cardiovascular disease Detect and manage complications

Anemia Hyperparathyroidism Bone disease Electrolyte abnormalities Vascular complications

Prevent CV disease
Most common cause of death is CV disease and not renal failure.

Smoking cessation Diabetes and Blood pressure control Lipids

No evidence that tx affects renal fxn Guidelines: ATP3 -> LDL goal < 100

Goals of Care
1.

2.
3.

Slow decline in renal function Prevent cardiovascular disease Detect and manage complications

Anemia Hyperparathyroidism Bone disease Electrolyte abnormalities Vascular complications

When to refer

Proteinuria > 3.5 gm in 24 hours Nephritis

Hematuria, proteinuria and HTN

Diabetes & CKD but no retinopathy GFR decline of 50% in one year Stage 3 or 4 CKD

Key Points

Think about CKD and screen

Creatinine AND urine protein

Calculate the GFR! Look for reversible cause if no DM Get to know the KDOQI guidelines & think about the complications