Chronic Kidney Disease
Sandeep Vetteth
Chronic Kidney Disease
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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?
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24 hour collection for proteinuria
Kidney USG
Measurement of Urine micro albumin
SPEP
Measurement of HbA1C
Chronic Kidney Disease
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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
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A
m
er
A
sia
ck
Bl
a
W
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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;
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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
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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
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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
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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
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Uncontrolled hyperkalemia and acidosis
Uncontrollable hypervolemia (pulmonary edema)
Pericarditis
AMS and somnolence (advanced encephalopathy)
Bleeding diathesis
► Indications
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(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
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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?
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Chlorthalidone
Losartan
Metoprolol
Minoxidil
Amlodipine