Chronic Kidney DiseaseChronic Kidney DiseaseChronic Kidney DiseaseChronic Kidney Disease

Darrell Gray, II MDDarrell Gray, II MD

Internal MedicineInternal Medicine

Tenwek HospitalTenwek Hospital

DefinitionsDefinitions

CKD = > 3 months of ↓ glomerular filtration rate (GFR) +/- kidney damage as evidenced by serology, imaging or pathology

GFR= (140 – age) x LBW (kg) x Constant

serum Creat (in µmol/L)

Constant: 1.23 for men; 1.04 for women

How do we apply GFR? . . . in StagingHow do we apply GFR? . . . in Staging

How does CKD develop?How does CKD develop?How does CKD develop?How does CKD develop?

Common pathway

Initial Pathologic Insult

Reduced Nephron Mass

Glomerular Injury

Growth Promoters Acting on Intact

Glomeruli

End-Stage Kidney

Glomerular Hypertrophy on intact Glomeruli

Ok, but what are the clinical features?Ok, but what are the clinical features?

• General– Malaise, nausea, anorexia, pruritis, metallic taste, uremic

fetor (fishy breath), coma

• By system– Skin: White crystals in and on skin (uremic frost), dry scaly

skin, easy bruising– Neurologic: encephalopathy, neuropathy, seizures– Cardiovascular: HTN, HL, CHF, pericarditis, friction rub– GI: gastritis, ulcers, AVMs, pancreatitis

More clinical featuresMore clinical features

– Metabolic: Acidosis, ↑K+, ↑PO4, ↓Ca, ↑PTH• Acidosis 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

More about metabolic signsMore about metabolic signsMore about metabolic signsMore about metabolic signs

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.

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

Hypoaldosteroneism can develop hyperkalemia without a severely depressed GFR.

Calcium Phos PTH Process Treatment

↓ ↓ ↑ Vit D def 1,25 OH Vit D

↓ ↑ ↑ 2º hyperPTH

Phos

Binders

↓ ↑ ↑↑↑ Severe 2º hyperPTH

Phos binders and Vit D

↑ variable ↓ Excessive Ca/VitD replcmnt

Stop replcmnt

So my pt presents with concerning Hx So my pt presents with concerning Hx and PE. What studies to do I need??and PE. What studies to do I need??

• Labs– K+, Creatinine, Ca++, Mg, Phos– Urinalysis– Strict I/O– Daily weight

• Imaging– Kidney ultrasound

• Small kidneys bilaterally

But don’t forget !!But don’t forget !!

• Medications– Renally dose medications such as

antibiotics/antiretrovirals, ranitidine, atenolol– Be extremely cautious with starting an ACEI or ARB.

Talk with consultant.– Avoid using Morphine as toxic metabolites build up.– If diuresis is necessary, use lasix if patient has

hyponatremia, and thiazide if pt has hypernatremia• However, thiazides are not effective when GFR <30

Causes of Chronic Renal FailureCauses of Chronic Renal FailureCauses of Chronic Renal FailureCauses of Chronic Renal Failure

• Glomerulonephritis

• HTN

• Diabetic nephropathy

• Pulmonary-renal syndromes

• Systemic diseases

• Urinary tract pathology

• Congenital

GlomerulonephritidesGlomerulonephritidesGlomerulonephritidesGlomerulonephritides

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).

Hypertension / Renovascular Hypertension / Renovascular DiseaseDisease

Hypertension / Renovascular Hypertension / Renovascular DiseaseDisease

Nephrosclerosis Ischemic Renal Disease

– Abdominal bruits.– Atherosclerotic disease elsewhere.– ARF on ACE inhibitors.

Pulmonary -Renal SyndromesPulmonary -Renal SyndromesPulmonary -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 DiseasesSecondary to Systemic DiseasesSecondary to Systemic Diseases

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

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

Urinary Tract DiseaseUrinary Tract DiseaseUrinary Tract DiseaseUrinary Tract Disease

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

obstruction.

CongenitalCongenitalCongenitalCongenital

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 Therapy of Chronic Renal FailureFailure

Therapy of Chronic Renal Therapy of Chronic Renal FailureFailure

Diet TherapyDiet TherapyDiet 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.

One Suggested ApproachOne Suggested Approach

Phosphate ControlPhosphate ControlPhosphate ControlPhosphate Control

Dietary phosphate should be restricted. Phosphate binders must be given with meals. Calcium carbonate usually first choice, but as disease

progresses may need to switch to calcium acetate or non calcium containing binders such as sevelamer or lanthanum carbonate.

Aluminum hydroxide binders should be avoided if possible.– Use with citrate solutions has resulted in aluminum

toxicity and death.

PTH ControlPTH Control

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

• In addition, calcimimetic such as cinacalcet may also be needed to lower iPTH.

• Issues currently revolve around iPTH/Ca/PO4 and cardiac risk.

HypertensionHypertensionHypertensionHypertension

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.

What Does Good Care do?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 recommendationsSummary 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) Early referral to nephrologist (Cr>1.7)