Chronic Kidney Disease



    Chronic Kidney Disease

    See KDIGO guidelines 2012 on management for details


    For KDIGO guidelines 2012 click HERE


    External Link: KDIGO.ORG CKD Section



    • Managing hypertension is indicated for all patients with kidney disease. (regardless of etiology)
    • Controlling blood pressure helps to decrease cardiovascular risk and may help to prevent progression to end-stage kidney disease. 
    • ACEi/ARB are preferred Anti-HTN agents in CKD, especially in those with proteinuria. 
    • Mechanism:
      • ACEi/ARB lower efferent arteriolar resistance and lower intraglomerular pressure. 
      • The lower intraglomerular pressure is thought to be protective for the kidney but may be associated with a slight increase in the serum creatinine level (30% increase is acceptable).
      • CAUTION: Use of these agents also may cause hyperkalemia.  Use diuretics to manage hyperkalemia, further HTN, and edema. 
      • Higher doses of diuretics are often required.


    Metabolic Acidosis

    • Metabolic acidosis develops when GFR delines (usually < 30)
    • de Brito-Ashurst et al (2009): RCT comparing sodium bicarb to no treatment.
      • Treatment had lower annual decline in renal function, lower creat, less dialysis. 
      • Many had concerns over sodium load, but BP did NOT increase in the study.
      • Therefore: use sodium bicarb to target HCO3 of >22 mEq/L in patients with metabolic acidosis and GFR < 30 (Stage IV CKD)
        • Benefits: slows progression of CKD, slows metabolic bone disease, improves nutrition status. 

    Chronic Tubulointerstitial Disorders

    • Can evolve from Acute Interstitial Nephritis
    • Damage to the tubules and interstitium 



    • Low Hb (Epo producing cells destroyed)
    • Urine:
      • Urinalysis - bland or sterile pyuria
      • Urine Protein - usually low-molecular weight (<2g/24hrs)
    • Ultrasound - small atrophic kidneys
    • Biopsy Indications:
      • Unclear Etiology (possible change in therapy based on results)





    Causes of Chronic Tubulointerstitial Disorders

    Category Explanation

    Autoimmune disorders


    Sjogren's Syndrome

    • Can happen in 25-50% of Sjogren's
    • Seen in first few years of disease (can precede onset of other manifestations)
    • Steroids can improve the course of the disease


    • Non-Casceating Granulomas Interstitial Nephritis
      • (Classic renal involvement)
      • Can happen without granulomas
    • Hypercalcemia, Nephrocalcinosis, Nephrolithiasis
    • Treatment:
      • Corticosteroids can improve renal function


    • More commonly glomerular disease, but many patients get immune complex deposites in tubular basement membranes
    • Can treat with immunosuppresants


    Anti–tubular basement membrane antibody-mediated tubulointerstitial nephritis

    Tubulointerstitial nephritis with uveitis


    Balkan endemic nephropathy

    Heavy metal nephropathy


    - Gout!

    - Serum lead levels aren't helpful (most is in bone)

    - EDTA mobilization testing with 24hr urine lead excretion (>600mcg/24hrs  = diagnostic)




    Hereditary tubulointerstitial


    Medullary cystic disease (type II is associated with hyperuricemia and gout)

    - Urate Nephropathy (alkaline urate salts deposit into interstitium, causing inflammation -- nephritis)


    Mitochondrial disorders


    Direct infiltration or reactive systemic inflammatory response can cause this. 

    Risk factors: 

    • Transplant
    • Elderly
    • Immunocompromized (chemo, or chronic immunosuppressants, HIV)


    • TB, EBV, CMV, Polyoma BK Virus (transplant recipients), etc...
    • Brucellosis, Fungal infections, Legionella species, Toxoplasmosis


    Mostly multiple myeloma & lymphoproliferative disorders

    Multiple Myeloma: 

    • 50% have renal involvement at time of dx. 
    • Myeloma cast nephropathy - precipitation of Bence Jones protein in renal tubule acutely (tubular toxicity).
      • multinucleated tubular giant cells in tubular walls 
      • Tubular obstruction, injury
    • Risk Factors: Volume Depletion, Hypocalcemia
    • Myeloma light chain deposition can occur months-to-years, can lead to proximal RTA (fanconi syndrome) [see Renal Tubular Acidosis Section]
    • Treatment:
      • Treat Hypercalcemia
      • Correct volume status
      • Treat Myeloma

    Lymphoproliferative Disorders

    • 50% have renal involvement on post-mortem exam
    • Present with non-nephrotic range proteinuria, sterile pyuria, large kidneys. 
    • Treatment
      • Treat malignancy


    Analgesic nephropathy

    - ASA, Phenacitin ("father of acetaminophen"), Caffeine, etc...

    - Association with NSAIDs is not as robust (exposure to large

      quantities linked to CKD) - dose-dependent

    - (highest toxicity with combination therapy)

    - Also linked to upper urinary malignancies (if hematuria = need investigations)

    Treatment: Discontinue Analgesics (often improve)


    Calcineurin inhibitors (secondary tubulointerstitial injury consequent to arteriolopathy)

    Chinese herb nephropathy (aristolochic acid)


    - Dose dependent, and length-dependent (chronic tubulo-int. nephritis)

    - Distal RTA (reabsorbs in same sites as Na+ --> uptake in renal tubules)

    Treatment: Can use amiloride, blocks Lithium reabsorption. 



    Prolonged exposure to any medication that can cause acute interstitial nephritis

    5-Aminosalicylates (e.g., mesalamine)




    H2 blockers



    Proton pump inhibitors



    Secondary Tubulointerstitial


    glomerular and vascular disorders

    Urinary Tract Obstruction

    Functional or structural 

    - Obstruction & relfux --> inflammation of interstitium --> atrophy



    • Catch early and treat underlying cause  (early ones can be reversed)
    • Approach:
      • Stop drugs
      • Removal of exogenous toxins
      • Diagnose immunologic, infectious, or malignant disease
      • Rule out obstruction
      • Treat underlying cause
      • Consider immunsuppressants in consultation with nephrologist

    GFR Estimation

    • Ways to estimate:
      • Modification of Diet in Renal Disease (MDRD) study
        • Underestimates GFR at higher (normal) values.
        • If calculated eGFR is >60 mL/min/1.73m^2 then report as 60.
        • Study included patients with CKD with lower muscle mass than general population.
          • Underestimates GFR in healthy, low-risk persons with normal/increased muscle mass.
      • Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)
        • Reduced bias associated with MDRD, shown in NHANES study.
          • NHANES: median eGFR was 94.5 mL/min/1.73m^2 using CKD-EPI and 85 using MDRD.
        • Some patients Stage 3 CKD via MDRD and no CKD by CKD-EPI.
      • Cockcroft-Gault
        • Underestimates GFR at higher values.
        • Less accurate than MDRD and CKD-EPI?
      • 24-hour urine collection - for Creat Clearance.
        • Good but inaccurate due to difficulty in collecting 24-hr urine sample.
        • Undercollection = inaccurate GFR.
      • Radionucleotide kidney clearance scanning
        • Very accurate, but more invasive and expensive than eGFR.
        • Often used in evaluating live kidney donors.
    • CKD Stage GFR level (mL/min/1.73 m2)
      Stage 1 ≥ 90
      Stage 2 60 - 89
      Stage 3 30 - 59
      Stage 4 15 - 29
      Stage 5 < 15





    In addition to dietary counseling regarding a low phosphate diet, this patient with stage G4/A1 chronic kidney disease (CKD) who now has hyperphosphatemia should begin taking a phosphate binder such as sevelamer. Elevated serum phosphorus levels, particularly exceeding 6.5 mg/dL (2.09 mmol/L), are closely associated with increased mortality. Most patients with severe CKD require oral phosphate binders to be administered with meals. This patient also has known cardiovascular disease and vascular calcification. The Kidney Disease Improving Global Outcomes (KDIGO) guidelines suggest avoiding the use of calcium-containing phosphate binders in patients with known vascular calcification due to the potential for an increase in calcium absorption and worsening calcification of vessel walls. Therefore, a non-calcium–containing phosphate binder such as sevelamer or lanthanum is the preferred agent for this patient. Ferric citrate, another non-calcium–containing phosphorus binder, was recently approved for use in patients receiving dialysis but is not yet approved for patients with non-dialysis CKD.

    Although this patient has secondary hyperparathyroidism, administration of calcitriol will increase intestinal absorption of calcium and phosphorus, which will exacerbate the hyperphosphatemia and potentially worsen vascular calcification.

    Although administration of oral calcium carbonate will lead to increased absorption of calcium that may treat this patient's mild hypocalcemia and reduce her parathyroid hormone (PTH) levels, it may exacerbate vascular calcium in the setting of severe hyperphosphatemia.

    Administration of the calcimimetic cinacalcet will likely decrease this patient's PTH level toward the normal range; however, it will worsen her hypocalcemia and is not an effective treatment for the hyperphosphatemia.

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