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Chronic Kidney Disease

Sandeep Vetteth

Chronic Kidney Disease

A 54 year old woman is evaluated for a Cr of 1.3; 18


months ago it was 0.9. She has a 5 year history of DM 2,
dyslipidemia and HTN well controlled with lisinopril, HCTZ,
and atenelol. She is also on glipizide and simvastatin.
Hemoglobin is normal. What is the most appropriate for
this patient?

24 hour collection for proteinuria


Kidney USG
Measurement of Urine micro albumin
SPEP
Measurement of HbA1C

Chronic Kidney Disease

In the United States, there is a rising incidence and


prevalence of Kidney Disease.
Nearly 350,000 of these are on dialysis.
Also, there is an increasing prevalence of earlier stages of
chronic kidney disease which unfortunately is underdiagnosed and under-treated in the United States.
In 2000, the National Kidney Foundation (NKF) Kidney
Disease Outcomes Quality Initiative (K/DOQI) Advisory
Board approved development of clinical practice guidelines
to define chronic kidney disease and to classify stages in
the progression of chronic kidney disease.

Stages of Chronic Kidney Disease


Stage 1

Kidney damage with


normal or GFR

GFR 90 ml/min/1.73
m2

Stage 2

Kidney damage with


mild GFR

GFR 60-89

Stage 3

Moderate GFR

GFR 30-59

Stage 4

Severe GFR

GFR 15-29

Stage 5

Kidney failure

GFR <15 (or dialysis)

Causes of End Stage Renal Disease

In
di
an

n
A
m

er

A
sia

ac
k
Bl

hi
te

Other
Interstit N
Cystic KD
GN
BP
Diabetes

A
ll

100%
90%
80%
70%
60%
50%
40%
30%
20%
10%
0%

USRDS Annual Data Report

Chronic Kidney Disease


Many

terms are used to describe states of


reduced glomerular filtration (GFR) not requiring
renal replacement therapy;

Chronic Renal Insufficiency


Chronic Renal Failure
Renal Insufficiency
Pre dialysis renal disease
Pre uremia
Renal dysfunction

They

are imprecise & poorly defined.

Chronic Kidney Disease


Measurement

of GFR

Gold standard is Inulin Iothalamate.


Creatinine Clearance calculated by timed (24h) urine
collection along with serum collection for Creatinine.
Overestimate GFR when CKD is severe due to an
increase in tubular secretion of creatinine.
This factor can be corrected by cimetidine.
Estimation

of GFR

More than 10 formulae for estimation of GFR.


MDRD most widely accepted now.

CKD Risk Factors


Diabetes

Mellitus
Hypertension
Cardiovascular Disease
Obesity
Metabolic Syndrome
Age and Race
Acute Kidney Injury
Malignancy

Family

history of CKD
Kidney Stones
Infections like Hep C
and HIV
Autoimmune diseases
Nephrotoxics like
NSAIDS

CKD - Causes
Diabetic
Non

Diabetic

Glomerular
Nephritic:

PIGN, IgA, MPGN


Nephrotic: FSGS, Membranous, Amyloidosis

Tubulointerstitial: Analgesic, Reflux, Ch. Obs


Vascular: Vasculitis, HTN, RAS
Cystic: ADPKD
CKD in transplantation

CKD - Causes

CKD - Manifestations

Abnormal Sodium-Water metabolism


Edema, Hypertension
Abnormal Acid-base abnormalities
Metabolic Acidosis due to uremia or RTA
Abnormal hematopoesis
Anemia of CKD
Cardiovascular Abnormalities
LVH, CAD, Diastolic Dysfunction
Abnormal Calcium-Phosphorus metabolism
Hyperphosphatemia, pruritus, arthralgia
Hyperparathyroidism
Renal Osteodystrophy

CKD - Management

CKD - Management
Diagnostic

work up to decide underlying etiology


Treatment of Hypertension and Dyslipidemia
Treatment of Anemia
Treatment of Hyperphosphatemia
Avoidance of Dehydration & Nephrotoxic agents
Proper Dosing of Drugs
Preparation for Renal Replacement Therapy

CKD - Evaluation

CKD - Evaluation
Serum

electrolytes
Urine spot protein analysis (24 hour no longer
recommended).
ANA, C3, C4
SPEP, UPEP
Kidney Ultrasound
Urine sediment analysis
Biopsy
Evidence of glomerular disease without diabetes
Sudden onset of nephrotic syndrome or glomerular
hematuria

CKD - Management
Diagnostic

work up to decide underlying etiology


Treatment of Hypertension and Dyslipidemia
Treatment of Anemia
Treatment of Hyperphosphatemia
Avoidance of Dehydration & Nephrotoxic agents
Proper Dosing of Drugs
Preparation for Renal Replacement Therapy

CKD - Hypertension
Anti-Hypertensive

Agents

Single most important measure could be adequate BP


control
Target BP <130/80 with minimal proteinuria and
BP<125/75 with significant proteinuria (>1g).
ACEIs and ARBs have been demonstrated to slow both
diabetic and non-diabetic renal disease in both
experimental and human studies.
Decrease the sodium intake to 2.5 g /day
Usually requires more than 2 medications.
Diuretics enhance the antihypertensive and
antiproteinuric effects of other agents..

CKD - Dyslipidemia
Dyslipidemia

and Cardiovascular morbidity

Several studies like the 4D study showed no


benefit of statins in dialysis patients.
However, post hoc analysis of this data does
suggest that the management of dyslipidemia
in CKD 2 4 improves cardiac mortality and
morbidity.
Dyslipidemia is frequently seen in glomerular
disease with proteinuria (nephrotic syndrome)
and its control reduces atherosclerosis related
morbidity and mortality.

CKD - Management
Diagnostic

work up to decide underlying etiology


Treatment of Hypertension and Dyslipidemia
Treatment of Anemia
Treatment of Hyperphosphatemia
Avoidance of Dehydration & Nephrotoxic agents
Proper Dosing of Drugs
Preparation for Renal Replacement Therapy

CKD - Anemia
Decreased

quality of
life with anemia.
Diagnosis of exclusion.
Mostly apparent in the
stage 4 and 5 of CKD.
Due to decrease in
EPO production in the
kidney.

CKD - Anemia
Erythropoietin

Epoetin alfa :Procrit , Epogen


Darbepoietin Alpha: ARANESP
Target

Hg levels between 11g and 12g but


not exceeding 13g.
Greater than 13g showed increased
mortality as per the CHOIR study.
Sufficient Iron should be administered to
correct iron stores.

CKD - Management
Diagnostic

work up to decide underlying etiology


Treatment of Hypertension and Dyslipidemia
Treatment of Anemia
Treatment of Hyperphosphatemia
Avoidance of Dehydration & Nephrotoxic agents
Proper Dosing of Drugs
Preparation for Renal Replacement Therapy

CKD - Hyperphosphatemia
Control

of Hyperphosphatemia

Due to decreased excretion in urine.


Control of hyperphosphatemia by dietary measures slow
progression in experimental models of CKD.
Hyperphosphatemia leads to pruritus, calcification in
synovial membranes, blood vessels and even cardiac
valves.
Therapy includes Phosphorus restriction to 800mg/day
and use of phosphrous binders with food.
Calcium

Carbonate (TUMS), Ca-acetate (PHOSLO)


Lanthanum
Renagel

CKD Bone and Mineral disease


Hyperparathyroidism:

High phosphorus and low Vitamin D causing low


calcium.
Monitor Intact PTH levels and keep between
100 and 500.
Maintain Phosphorus and Calcium within normal
ranges.
Vitamin D analog paricalcitol.
Calcimimetic agents like cinacalcet.

CKD - Management
Diagnostic

work up to decide underlying etiology


Treatment of Hypertension and Dyslipidemia
Treatment of Anemia
Treatment of Hyperphosphatemia
Avoidance of Dehydration & Nephrotoxic agents
Proper Dosing of Drugs
Preparation for Renal Replacement Therapy

CKD - Nephrotoxics
Avoidance

of Dehydration/Nephrotoxic Agents

Drugs such as Aminoglycosides, NSAIDs


Avoiding exposure to Radio contrast agents.
In presence of dehydration, even in absence of
renovascular disease, ACEIs or ARBs can aggravate
renal dysfunction
Dehydration is frequent in tubulo-interstitial disorders
where urinary concentration is impaired.
Proper Dosing of Drugs eg. Allopurinol

CKD - Management
Diagnostic

work up to decide underlying etiology


Treatment of Hypertension and Dyslipidemia
Treatment of Anemia
Treatment of Hyperphosphatemia
Avoidance of Dehydration & Nephrotoxic agents
Proper Dosing of Drugs
Preparation for Renal Replacement Therapy

CKD Medication Dosing


Proper

Dosing of Drugs

Uremia affects GI absorption; eg Iron.


Impaired plasma protein binding of drugs; eg Dilantin.
Increased volume of distribution;
Excretion of many drugs depends upon the kidney;
Some

drugs used in normal dose will lead to nephrotoxic effects


eg. Allopurinol
Other drugs when used in normal dose will lead to other toxic
effects eg. Vancomycin.

Dose

Reduction or Interval Extension

CKD - Management
Diagnostic

work up to decide underlying etiology


Treatment of Hypertension and Dyslipidemia
Treatment of Anemia
Treatment of Hyperphosphatemia
Avoidance of Dehydration & Nephrotoxic agents
Proper Dosing of Drugs
Preparation for Renal Replacement Therapy

CKD - RRT
Preparation

for Renal Replacement Therapy

Education for Options of Dialysis & Renal


Transplantation for Renal Replacement
Hemodialysis Vs Peritoneal Dialysis
Avoidance of Veni-puncture & insertion of
catheters in peripheral veins once GFR < 60mls.
Timely placement of vascular access or PD
catheter.

CKD - RRT
Indications

Uncontrolled hyperkalemia and acidosis


Uncontrollable hypervolemia (pulmonary edema)
Pericarditis
AMS and somnolence (advanced encephalopathy)
Bleeding diathesis

Indications

(Absolute):

(Relative):

Nausea, vomiting and poor nutrition


Metabolic acidosis
Lethargy and Malaise
Worsening kidney function <10 ml or <15 ml in diabetics

CKD - RRT
Transplantation:

Preemptive transplant
carries both patient and
graft survival
advantage.
Graft survival better
with living donor
kidneys.
Immunosuppresion is
almost always a must.

CKD - RRT
Transplantation:

Diseases like FSGS may reccur early in the


transplanted kidney.
Increased risk for infection, bone loss,
cardiovascular disease.
Contraindications:
Malignancy

(recent or metastatic)
Current infection
Severe extra renal disease
Active use of illicit drugs

CKD - Summary
In

creasing prevalence of CKD in the


population.
Early detection and prevention of
progression.
Early involvement of nephrologists in the
care (when GFR<30).
Treatment of Manifestations and
complications.
Renal Replacement Therapy
Timely referral for Access
Timely Transplant Work up.

Chronic Kidney Disease

A 70 yr old woman comes for F/U of recently diagnosed


CKD and HTN. She is asymptomatic. Her only medications
is Lisinopril which has been titrated to its maximum dose in
the last 3 months. She is compliant and uses salt
restriction. BP is 160/90. exam is normal except for trace
pedal edema. Cr is 1.3, K is 5 and Urine Prot is 2.1 gm.
Which of the following is the most appropriate treatment
for this patient?

Chlorthalidone
Losartan
Metoprolol
Minoxidil
Amlodipine