Chronic Kidney Disease

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Chronic Kidney Disease

• Sandeep Vetteth

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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

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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 under-diagnosed 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.

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Stages of Chronic Kidney Disease
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Causes of End Stage Renal Disease
USRDS Annual Data Report
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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.

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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.

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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

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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

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CKD - Causes
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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
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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

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CKD - Evaluation
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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

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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

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CKD - Hypertension

• Anti-Hypertensive Agents
• Single most important measure could be adequate
  BP control
• Target BP lt130/80 with minimal proteinuria and
  BPlt125/75 with significant proteinuria (gt1g).
• 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..

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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.

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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

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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.

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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.

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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

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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

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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.

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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

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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

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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

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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

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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

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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 lt 60mls.
• Timely placement of vascular access or PD
  catheter.

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CKD - RRT

• Indications (Absolute)
• Uncontrolled hyperkalemia and acidosis
• Uncontrollable hypervolemia (pulmonary edema)
• Pericarditis
• AMS and somnolence (advanced encephalopathy)
• Bleeding diathesis
• Indications (Relative)
• Nausea, vomiting and poor nutrition
• Metabolic acidosis
• Lethargy and Malaise
• Worsening kidney function lt10 ml or lt15 ml in
  diabetics

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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.

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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

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CKD - Summary

• In creasing prevalence of CKD in the population.
• Early detection and prevention of progression.
• Early involvement of nephrologists in the care
  (when GFRlt30).
• Treatment of Manifestations and complications.
• Renal Replacement Therapy
• Timely referral for Access
• Timely Transplant Work up.

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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