CRF – A Practical Overview

Dr. INAYAT ULLAHDepartment of General Medicine

Team I

CKD - Definitions Evidence of structural or functional kidney abnormalities

that persists for at least ≥3 months, with or without a decreased GFR, as manifested by either:

Pathological abnormalitiesMarkers of kidney damage, including

abnormalities in the composition of the blood or urine, or abnormalities in imaging tests

GFR <60 mL/min/1.73m² for ≥3 months, with or without kidney damage

GFR = (140 – age) x BW (kg) x Constant serum Creatinine (in µmol/L)

(Constant: 1.23 for men; 1.04 for women)

Application of GFR in stagingStage GFR

(ml/min/1.73m2)

Description

1 90 Normal or increased glomerular filtration rate (GFR), with other evidence of kidney damage

2 60–89 Slight decrease in GFR,with other evidence of kidney damage

3 30 – 45 Moderate decrease in GFRwith or without other evidence of kidney damage

4 15–29 Severe decrease in GFR, with or without other evidence of kidney damage

5 < 15 Established renal failure

Potential Risk Factors for Susceptibility to and initiation of CKD

Diabetes Hypertension Autoimmune disease Systemic infections Exposure to drugs

associated with acute decline in kidney function

Recovery from acute kidney failure

Older age Family history of kidney

disease Reduced kidney mass Racial/ethnic background Smoking

How does CKD Develop

Common pathway

Initial Pathologic Insult

Reduced Nephron Mass

Growth Promoters Acting on Intact

Glomeruli

End-Stage Kidney

Glomerular Hypertrophy on intact Glomeruli

Glomerular Injury

Ok, but what are the clinical features?

GeneralMalaise, nausea, anorexia, pruritis, metallic taste,

uremic fetor (fishy breath), coma

By systemSkin: White crystals in and on skin (uremic frost), dry

scaly skin, easy bruisingNeurologic: encephalopathy, neuropathy, seizuresCardiovascular: HTN, CCF, pericarditis, friction rubGI: gastritis, ulcers, AVMs, pancreatitis

More clinical features

Metabolic: Acidosis, ↑K+, ↑PO4, ↓Ca, ↑PTHAcidosis and hyperkalemia can become profound when

GFR< 20

Hematologic: Anemia, bleeding

Typically when GFR <30

Musculoskeletal: Osteomalacia, adynamic bone disease, metastatic calcifications, mixed bone disease

Endocrine: Insulin resistance, growth retardation, hypogonadism, impotence, infertility

Metabolic Derangements

Hyperphosphatemia, Hypocalcemia and Hypermagnesemia.

Decreased production of 1,25-dihydroxy vitamin D3 results in decrease GI Ca++ absorption.

Decreased ability of the kidney to excrete PO4-.

These result in a decrease in serum Ca++ which leads to an increase in PTH which results in increased bone reabsorbtion of Ca++ in an attempt to normalize free Ca+

+ levels and leads to renal bone disease.

Feedback Loops in SHPT

Ca = calcium; CVD = cardiovascular disease; P = phosphorus.

PTH

Bone DiseaseFracturesBone pain

Marrow fibrosisErythropoietin resistance

Serum P1,25D

Calcitriol

Renal Failure

PTH

Systemic ToxicityCVD

HypertensionInflammationCalcification

Immunological

25D

Ca++

Decreased Vitamin D Receptors and Ca-Sensing Receptors

Metabolic Derangements

Hyperkalemia

Gradual decrease in tubular handling of K+ can result in hyperkalemia.

Usually occurs when GFR severely reduced (<10 ml/min).K+ restriction often needed.Diabetics with Type IV RTA / Hyporeninemic

Hypoaldosteronism can develop hyperkalemia without a severely depressed GFR.

So my patient presents with concerning Hx and PE. What studies to do I need initially

Lab InvestigationsUrea/Creatinine,

K+/Na+, Ca++, Mg, PO4

Urinalysis

ImagingKidney ultrasound

Small kidneys bilaterally

Causes of Chronic Renal Failure

Glomerulonephritis HTN Diabetic nephropathy Pulmonary-renal syndromes Systemic diseases Urinary tract pathology Congenital

Glomerulonephritides

Idiopathic Membranous Glomerulonephritis. Focal and Segmental Glomerulonephritis (FSGS)

Associated with HIV IgA Nephropathy (Berger’s Disease). Membranoproliferative Glomerulonephritis Type I

and II (MPGN I and II).

Pulmonary -Renal SyndromesPulmonary -Renal Syndromes

Goodpasture’s Syndrome (anti-basement membrane disease)

Wegener’s Granulomatosis and other ANCA (antineutrophil cytoplasmic antibody) associated diseases.

Secondary to Systemic DiseasesSecondary to Systemic Diseases

Systemic Lupus Erythematosis (SLE). Other collagen vascular diseases. Microscopic polyarteritis (vasculitis). Thrombotic Microangiopathies (HUS, TTP, malignant

HTN). Multiple Myeloma (MM). Amyloidosis Henoch-Schonlien Purpura (HSP). Aids Nephropathy.

Urinary Tract DiseaseUrinary Tract Disease

Reflux Nephritis. Ureteral or Urethral Obstruction. Other causes of chronic or recurrent obstruction.

CongenitalCongenital Adult Polycystic Kidney Disease (APKD).

Most common inherited form of renal disease.Characterized by numerous cysts in both

kidneys.Cysts can also be present in liver, pancreas,

ovaries.Other findings can include mitral valve

prolapse, cerebral aneurysms, diverticular disease.

Alport’s Syndrome.

Therapy of Chronic Renal FailureTherapy of Chronic Renal Failure

Dietary AdjustmentsAdequate Glycaemic ControlControl of Blood PressureLower Lipid levelsCorrection of AnemiaTreatment of Sec Hyperparathyroidism

Goals

Diet TherapyDiet Therapy

Low sodium diet for blood pressure and volume control.

Maintain adequate nutrition.

No proof that low protein (< 0.8 g ptn / kg / day) slows progression although it may help in management of acidosis.

May need to use diuretics and fluid restrict for volume control.

Potassium restriction as needed.

Cholesterol treatment may be required.

Hypertension ControlHypertension Control

Good control of blood pressure can slow progression of renal failure.

Evidence that early use of ACE inhibitors in Type I diabetics with nephropathy slows the progression of renal disease.

Evidence to suggest this also applies to Type II diabetics.

Evidence for ARBs as first line in Type II diabetics.

Often used interchangeably or in combination.

Recommendations for BP and RAS Management in CKD

BP = blood pressure; RAS = renin angiotensin system; CCB = calcium channel blocker; BB = -blocker;

PatientGroup

Goal BP(mm Hg) First Line Adjunctive

+ Diabetes <130/80 ACE-I or ARB Diuretics then CCB or BB

Diabetes + Proteinuria

<130/80 ACE-I or ARB Diuretics then CCB or BB

Diabetes Proteinuria

<130/80 No specific preference:

Diuretics then ACE-I, ARB, CCB, or BB

EXPECT TO NEED TO USE 3+ AGENTS TO ACHIEVE GOALS

Anemia Treatment Eligibility

Should be treated especially if: Serum Creatinine (2.0 mg/dl or above) or Creatinine Clearance (45 ml/min or below) and Hemoglobin (11g/dl or below) or Hematocrit (33% or below) or Symptoms of anemia

Consequences of Anemia in CKDReduced oxygen delivery to tissuesDecrease in Hgb compensated by increased cardiac

outputProgressive cardiac damage and progressive renal

damageIncreased mortality riskReduced quality of life

FatigueDiminished exercise capacityReduced cognitive function

Left ventricular hypertrophy (LVH)

PTH Control

• Use of vitamin D analogs often needed to reduce PTH levels (calcitriol, paracalcitol or doxercalciferol).

• In addition, calcimimetic agents may also be needed to lower PTH.

What Does Good Care do?

Diabetic renal disease progression can be decreased from 12 ml/min/year to 4 ml/min/year.

Non diabetic renal disease progression can be slowed from 4-6 ml/min/year down to 2 ml/min/year.

These results are in established chronic disease with no active primary process.

Summary of recommendations

Aggressive BP control (<130/80) ACEI or ARB preferred

Excellent control of DM (HgBA1C<7%) Avoid renal insults (nephrotoxins, etc) Cardiovascular disease prevention (lipids, etc) Monitor for anemia Minimize bone disease Appropriate nutritional counseling Smoking cessation (for everybody, not just renal patients)

When conservative measures fail – Renal Replacement Therapy

When conservative management of ESRD is inadequate, consider

Haemodialysis, Peritoneal dialysis and Renal transplantation

Indications for DialysisAccording to the Kidney Disease Outcome Quality Initiative (KDOQI), dialysis is indicated in the following:

1. GFR ≤ 10 ml/min (≤ 15 ml/min in diabetics)

2. Serum Creatinine of 8 mg/dL (6 mg/dL in diabetics)

3. Uraemic Symptoms (encephalopathy, coagulopathy, pericarditis)

4. Fluid overload unresponsive to diuretics

5. Refractory hyperkalemia

6. Severe Metabolic Acidosis (pH ≤ 7.20)

7. Neurological symptoms (seizures or neuropathy)

Complications of DialysisSystem Complications

Cardiovascular Air Embolism

Angina

Arrythmia

Cardiac Tamponade

Hypotension

Infectious Bacteremia

Endocarditis

Osteomyelitis

Sepsis

Meningitis

Colonization of temporary central venous catheters

Vascular access cellulitis or abscess

Metabolic Hypoglycemia in diabetics who use insulin

Hypokalemia

Hyponatremia Hypernatremia

Miscellaneous Hemorrhage (GI, intracranial, retroperitoneal, intraocular)

Amyloid deposits

Seizures

Restlessness

Insomnia