Chronic Kidney Disease

1. Chronic Kidney Disease Darrell Gray, II MD Internal Medicine Tenwek Hospital

2. Definitions 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

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

4. How does CKD develop? Common pathway Initial Pathologic Insult Reduced Nephron Mass Growth Promoters Acting on Intact Glomeruli Glomerular Injury Glomerular Hypertrophy on intact Glomeruli End-Stage Kidney

5. 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

6. More 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

7. More 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.

8. 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.

10. So my pt presents with concerning Hx 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

11. 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

12. Causes of Chronic Renal Failure • Glomerulonephritis • HTN • Diabetic nephropathy • Pulmonary-renal syndromes • Systemic diseases • Urinary tract pathology • Congenital

13. 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).

14. Hypertension / Renovascular Disease • Nephrosclerosis • Ischemic Renal Disease • Abdominal bruits. • Atherosclerotic disease elsewhere. • ARF on ACE inhibitors.

15. Pulmonary -Renal Syndromes • Goodpasture’s Syndrome (anti-basement membrane disease) • Wegener’s Granulomatosis and other ANCA (antineutrophil cytoplasmic antibody) associated diseases.

16. Secondary 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.

17. Urinary Tract Disease • Reflux Nephritis. • Ureteral or Urethral Obstruction. • Other causes of chronic or recurrent obstruction.

18. Congenital • 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.

19. Therapy of Chronic Renal Failure

20. Diet 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.

21. May need to use diuretics and fluid restrict for volume control. • Potassium restriction as needed. • Cholesterol treatment may be required.

22. One Suggested Approach

23. Phosphate 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.

24. PTH 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.

25. Hypertension • 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.

26. 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.

27. 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) • Early referral to nephrologist (Cr>1.7)