CHRONIC KIDNEY

DISEASE
BY DR SAMEEHA ALSHELLEH
2018-2019
 CASE
• 65 YEAR OLD FEMALE REFERRED WITH DIABETIC
NEPHROPATHY, PROTEINURIA 3 G/DAY, EGFR 23
• DENIES NAUSEA, VOMITING, WEIGHT LOSS,
ANOREXIA. DOES NOTE MEAT AVERSION
• MEDS AMLODIPINE & HCTZ
• BP 150/90, PERIPHERAL EDEMA
• LABS: HB 8.9, K 5.6, CA 7.0, P04 6.0, PTH 300, LDL
140
 DEFINITION OF CKD
KIDNEY DISEASE OUTCOME QUALITY INITIATIVE (K/DOQI)

• KIDNEY DAMAGE FOR ³ 3 MONTHS, AS DEFINED BY

STRUCTURAL / FUNCTIONAL ABNORMALITIES, WITH OR
WITHOUT ¯ GFR, MANIFEST BY EITHER:
• PATHOLOGICAL ABNORMALITIES; OR
• MARKERS OF DAMAGE, INCLUDING ABNORMALITIES OF
• BLOOD TESTS
• URINE TESTS
• IMAGING

• GFR £ 60 ML/MIN/1.73 M2 FOR ³ 3 MONTHS, WITH

OR WITHOUT KIDNEY DAMAGE
STAGES OF CKD
 STAGES OF CKD
• STAGE 1 DISEASE
• NORMAL GFR (³ 90 ML/MIN)
• PERSISTENT ALBUMINURIA OR HEMATURIA
• STAGE 2 DISEASE
• GFR 60-89 ML/MIN
• PERSISTENT ALBUMINURIA OR HEMATURIA
• STAGE 3 DISEASE
• GFR 30-59 ML/MIN
• STAGE 4 DISEASE
• GFR 15-29 ML/MIN
• STAGE 5 DISEASE
• GFR < 15 ML/MIN OR ESRD
CAUSES OF CKD
 PROGRESSION OF CKD
• GFR TENDS TO DECLINE PROGRESSIVELY OVER TIME .
• RATE OF GFR DECLINE SHOULD BE ASSESSED TO
• PREDICT THE INTERVAL UNTIL THE ONSET OF ESRD .
• ASSESS EFFECT OF INTERVENTIONS TO SLOW THE GFR DECLINE.
• AMONG PATIENTS WITH CKD, THE RATE OF DECLINE
SHOULD BE ESTIMATED BY:
• COMPUTING FROM PAST AND ONGOING MEASUREMENTS OF
SERUM CREATININE;
• ASCERTAINING RISK FACTORS FOR FASTER GFR DECLINE .
• INTERVENTIONS TO SLOW PROGRESSION SHOULD BE
CONSIDERED IN ALL PATIENTS WITH CKD .
 PROGRESSION OF CKD (CONT)
• MEASUREMENTS OF CREATININE FOR ESTIMATION
OF GFR SHOULD BE OBTAINED AT LEAST YEARLY
• MORE OFTEN IN PATIENTS WITH:
• GFR <60 ML/MIN/1.73 M2;
• FAST GFR DECLINE IN THE PAST (>4 ML/ MIN/1.73 M2
PER YEAR);
• RISK FACTORS FOR FASTER PROGRESSION;
• ONGOING TREATMENT TO SLOW PROGRESSION;
• EXPOSURE TO RISK FACTORS FOR ACUTE GFR DECLINE.
 Initial injury
(GN, ATN, AIN, PCKD)
¯
Loss of renal parenchyma
¯
Adaptive hyperfiltration
(­ PGC ® ­ SNGFR ® wall stress ® ­ TGFß)
¯
Long-term damage
to remaining nephrons
¯
Proteinuria,
progressive renal
insufficiency
CHANGES IN RENAL HEMODYNAMICS
• INTRAGLOMERULAR HYPERTENSION (­PGC )

• COMPENSATORY RESPONSE TO NEPHRON

LOSS IN AN ATTEMPT TO MAINTAIN GFR
• PRIMARY AFFERENT VASODILATATION
• PRIMARY EFFERENT VASOCONSTRICTION
FALL IN GFR IS MINIMIZED BY ­ PGC
RESPONSE IS MEDIATED BY ¯ FLOW TO THE
MACULA DENSA AND ACTIVATION OF TGF
 MEASUREMENT OF GFR
• CREATININE
• EGFR (MDRD, COCKCROFT-GAULT)
• CREATININE CLEARANCE .
• CREATININE CLEARANCE + CIMETIDINE
• RADIONUCLIDE MARKERS .
• INULIN CLEARANCE .
• CYSTATIN C .
 CHARACTERISTICS OF AN IDEAL
MARKER

• CONSTANT PRODUCTION
• SAFE AND CONVENIENT
• READILY DIFFUSABLE IN ECF
• NO PROTEIN BINDING, FREELY FILTERABLE
• NO TUBULAR REABSORPTION OR SECRETION
• NO EXTRARENAL ELIMINATION OR DEGRADATION
• ACCURATE AND REPRODUCIBLE ASSAY
• MINIMAL INTERFERENCE WITH OTHER COMPOUNDS
• INEXPENSIVE
 COCKCROFT-GAULT
(140-AGE)*WT*1.2/CREATININE (X.85 IN
WOMEN)
• DERIVED FROM MEASURED CREATININE CLEARANCE IN A SMALL
POPULATION WITH CKD
• GIVES UNCORRECTED CREATININE CLEARANCE
• INCORPORATES AGE, WEIGHT, GENDER
• NO CORRECTION FOR BLACK RACE
• UNDER-ESTIMATES CREATININE CLEARANCE IN NORMAL PEOPLE
 MDRD – SIMPLIFIED

• DERIVED FROM STUDY OF PEOPLE WITH KIDNEY

DISEASE AT RISK OF PROGRESSION
• FACTORS FOR AGE, GENDER, RACE
• RESULT IS GFR IN ML/MIN/1.73 M2
• EGFR =186 X (SCR X .0113-1.154) X AGE-0.203 WITH
CORRECTIONS FOR BLACK/FEMALE
• UNDER-ESTIMATES GFR IN NORMALS
• NOT VALIDATED IN ASIANS, OLD AGE
 LIMITATIONS OF EGFR
• MDRD STUDY EQUATION IS REASONABLY
ACCURATE IN NON-HOSPITALIZED PATIENTS
KNOWN TO HAVE CKD.
• THE COCKCROFT-GAULT EQUATION IS LESS
ACCURATE IN INDIVIDUALS ABOVE OR BELOW
IDEAL BODY WEIGHT
• THE MDRD AND COCKCROFT-GAULT EQUATIONS
ARE LESS ACCURATE IN POPULATIONS WITH
NORMAL OR NEAR NORMAL GFR
• ESTIMATION EQUATIONS MAY BE LESS
ACCURATE IN POPULATIONS OF DIFFERENT
ETHNICITIES AND FROM OUTSIDE OF THE US.
 CYSTATIN C
• NON-GLYCOSYLATED 13-KDA PROTEIN .
• MEMBER OF FAMILY OF CYSTEINE PROTEASE
INHIBITORS .
• SYNTHESIZED BY ALL NUCLEATED CELLS .
• ENDOGENOUS PRODUCTION RATE IS CONSTANT .
• FREELY FILTERED BY THE GLOMERULUS .
• CATABOLIZED IN THE PROXIMAL TUBULE CELL .
• NOT INFLUENCED BY DIET, CONSTITUTIONAL FACTOR
• INVESTIGATIONAL .
 INVESTIGATION OF CKD

• ACUTE OR CHRONIC:
• URINALYSIS – LOOK FOR HEMATURIA, PROTEINURIA,
RBC CASTS (ACTIVE URINE)
• KIDNEY SIZE (USEFUL IF SMALL)
• PREVIOUS SERUM CREATININE VALUES
• HEMOGLOBIN, MINERAL METABOLISM
• FOLLOW-UP SERUM CREATININE
 INVESTIGATION OF CKD

WHO TO BIOPSY?
• EARLY > LATE
• YOUNG > OLD (HEREDITARY NEPHRITIS, FABRY ETC.)
• HEMATURIA > BLAND
• HEAVY PROTEINURIA > NONE .
• NORMAL KIDNEY SIZE > SMALL .
• NO EXPLANATION FOR CKD > HYPERTENSION,
VASCULAR DISEASE, DIABETES .
APPROACH TO DIAGNOSIS AND
TREATMENT AT THREE STAGES
FACTORS IMPLICATED IN PROGRESSION

• SYSTEMIC HYPERTENSION .
• PROTEINURIA .
• HYPERLIPIDEMIA .
• DIETARY PROTEIN .
• ANGIOTENSIN II, ALDOSTERONE .
• METABOLIC ACIDOSIS .
• HYPERPHOSPHATEMIA .
• HYERURICEMIA .
 GENERAL MANAGEMENT OF CKD

• TREATMENT OF REVERSIBLE CAUSES .

• PREVENTING / SLOWING PROGRESSION .
• TREATMENT OF COMPLICATIONS .
• IDENTIFICATION, EDUCATION, PREPARATION OF PATIENTS WHO WILL
REQUIRE RRT .
 PREVENTING PROGRESSION
• ¯ PROTEIN EXCRETION
• TARGET = < 0.5 TO 1 G/DAY (PCR < 60)
• REGIMENS SHOULD INCLUDE ACEI OR ARB
• IF TARGET IS NOT REACHED, COMBINE ACEI AND ARB
• ¯ BLOOD PRESSURE
• TARGET = < 130/80
• REGIMENS SHOULD INCLUDE ACEI OR ARB
• IF TARGET NOT REACHED, ADD DIURETICS, ADDITIONAL
MEDS
 PREVENTING PROGRESSION
• OTHER THERAPEUTIC MODALITIES (LESS EVIDENCE)
• ¯ PROTEIN INTAKE TO 0.8 TO 1.0 G/KG/DAY
• TREATMENT OF HYPERLIPIDEMIA
• TREATMENT OF METABOLIC ACIDOSIS
• TARGET HCO3 = 22 MMOL/L
• SMOKING CESSATION
 COMPLICATIONS OF CKD
• ECFV OVERLOAD
• SODIUM RESTRICTION
• DIURETIC THERAPY
• HYPERKALEMIA
• LOW K+ DIET
• DIURETICS
• KAYEXALATE
• METABOLIC ACIDOSIS
• TARGET HCO3 = 22 MMOL/L
• SODIUM BICARBONATE 0.5-1 G PO BID OR TID .
 COMPLICATIONS OF CKD
• HYPERPHOSPHATEMIA:
• BEGINS ~ STAGE 3 CKD
• TARGET = 0.87 AND 1.49 MMOL/L
• LOW PO4 DIET
• PO4 BINDERS (CACO3, SEVELAMER)
• RENAL OSTEODYSTROPHY:
• PTH INCREASES ~ STAGE 2, 3 CKD
• TARGET DEPENDS ON GFR (AVOID ¯ PTH ® ADYNAMIC
BONE DISEASE)
• PO4 BINDERS
• VIT D3 DECREASES WITH STAGE 3 CKD
• CALCITRIOL 0.25 ΜG/DAY
 COMPLICATIONS OF CKD
• HYPERTENSION
• TARGET BP < 130/80
• ACEI AND/OR ARB
• LOOP DIURETIC, NON-DIHYDROPERIDINE CCB

• ANEMIA
• COMMON WITH ³ STAGE 3 CKD
• TARGET HB ?
• EXCLUDE NON-RENAL CAUSES
• TREAT WITH ERYTHROPOIETINS AND IRON SUPPLEMENTATION
 WHEN TO REFER TO A NEPHROLOGIST
• POTENTIAL BENEFITS OF EARLY REFERRAL
• INFORMED SELECTION OF DIALYSIS MODALITY
• TIMELY PLACEMENT OF APPROPRIATE DIALYSIS ACCESS
• NON-EMERGENT INITIATION OF DIALYSIS
• LOWER MORBIDITY AND IMPROVED REHABILITATION
• LESS FREQUENT AND SHORTER HOSPITAL STAYS
• LOWER COST
• IMPROVED SURVIVAL
• PREEMPTIVE TRANSPLANT
WHEN TO REFER TO A NEPHROLOGIST

• ACUTE RENAL FAILURE

• EGFR < 30 ML/MIN
• PROGRESSIVE LOSS OF RENAL FUNCTION
• PERSISTENT PROTEINURIA
• PRESENT ON 2 OF 3 SAMPLES
• PCR > 60 (CORRESPONDS TO > 500 MG/DAY)
• INABILITY TO ACHIEVE RECOMMENDED TARGETS FOR
BLOOD PRESSURE
• INABILITY TO INITIATE RENO-PROTECTIVE STRATEGIES
 DEFINITION OF LATE REFERRAL

• WHEN MANAGEMENT COULD HAVE BEEN IMPROVED BY EARLIER

CONTACT WITH RENAL SERVICES.
• WITHIN ONE TO SIX MONTHS OF THE REQUIREMENT FOR RENAL
REPLACEMENT THERAPY
 PREPARING FOR DIALYSIS

• PRE-DIALYSIS CARE IS RECOMMENDED TO BEGIN AT

STAGE 4 CKD (EGFR £ 30 MLS/MIN)
• IDEAL TIME IN PRE-DIALYSIS CARE IS 1 YEAR TO
ALLOW FOR
• MODALITY EDUCATION
• SHOULD BE PROMOTING AUTONOMY, SELF MANAGEMENT ®
SELECTION OF HOME MODALITIES IN A MAJORITY OF PATIENTS
• PLACEMENT OF BODY ACCESS
• VASCULAR ACCESS FOR HD MUST BE PLACED ~ 3 MONTHS PRIOR
TO HD INITIATION TO ALLOW MATURITY
• PD CATHETER MUST BE PLACED ~ 1 WEEK PRIOR TO INITIATION
OF PD
 WHEN TO INITIATE DIALYSIS
• REFRACTORY FLUID OVERLOAD, CHF EXACERBATION
• HYPERKALEMIA (K >6) UNCONTROLLED BY DIET AND/OR KAYEXALATE
• SIGNS OF UREMIA
• METABOLIC ACIDOSIS UNCONTROLLED BY SODIUM BICARBONATE
• ?EGFR
 WHAT ARE CHOICES FOR PATIENTS
WITH STAGE 5 CKD?
• PRE-EMPTIVE LIVING DONOR TRANSPLANT
• SIB, SPOUSE, PARENT, CHILD, FRIEND

• HOME-BASED DIALYSIS TREATMENT:

• PERITONEAL DIALYSIS
• HOME HEMODIALYSIS (NOCTURNAL)

• CENTER HEMODIALYSIS
• HOSPITAL, CLINIC
• SELF CARE
 HEMODIALYSIS

• 3 POSSIBLE SCHEDULES
• CONVENTIONAL – 4 H, 3 DAYS/WEEK
• SHORT DAILY – 2-3 H, 4-6 DAYS/WEEK
• NOCTURNAL – 6-8 H, 3-6 DAYS/WEEK
• ACCESS TO CIRCULATION
• ARTERIOVENOUS FISTULA
• ARTERIOVENOUS GRAFT
• INTERNAL JUGULAR CUFFED CATHETER (UC CATHETER)
 PERITONEAL DIALYSIS

• PD CATHETER
• 2 SCHEDULES
• CAPD – 4-5 EXCHANGES OF 2-2.5 L/D
• CCPD – CYCLER ASSISTED OVERNIGHT DIALYSIS PLUS DAYTIME DWELL
 CASE
• 65 YEAR OLD FEMALE REFERRED WITH DIABETIC
NEPHROPATHY, PROTEINURIA 3 G/DAY, EGFR 23
• DENIES NAUSEA, VOMITING, WEIGHT LOSS,
ANOREXIA. DOES NOTE MEAT AVERSION
• MEDS AMLODIPINE & HCTZ
• BP 150/90, PERIPHERAL EDEMA
• LABS: HB 8.9, K 5.6, CA 7.0, P04 6.0, PTH 300, LDL
140